WO2021243835A1 - 高强度和韧性的光交联水凝胶材料及其制备方法与应用 - Google Patents

高强度和韧性的光交联水凝胶材料及其制备方法与应用 Download PDF

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WO2021243835A1
WO2021243835A1 PCT/CN2020/106113 CN2020106113W WO2021243835A1 WO 2021243835 A1 WO2021243835 A1 WO 2021243835A1 CN 2020106113 W CN2020106113 W CN 2020106113W WO 2021243835 A1 WO2021243835 A1 WO 2021243835A1
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component
group
photo
strength
tough
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孙宇
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中山光禾医疗科技有限公司
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Priority to US17/993,884 priority Critical patent/US11787903B2/en

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Definitions

  • the invention belongs to the field of biological materials, and particularly relates to a high-strength and tough photo-crosslinked hydrogel material, and a preparation method and application thereof.
  • Hydrogel is a kind of highly water-containing polymer material with a three-dimensional network cross-linked structure. Because of its excellent biocompatibility and certain mechanical strength, it can highly fit the microenvironment of biological tissues, so it is widely used in tissues. Engineering and regenerative medicine. In clinical applications, hydrogels cured in situ have excellent tissue shaping capabilities. Photosensitive hydrogels are more practical in clinical practice due to their precise controllability in time and space and in-situ light curing. However, the current photo-crosslinked hydrogels have poor mechanical properties. The strength of traditional photo-crosslinked hydrogels is only tens of kilopascals.
  • Chinese patent CN201711132472.2 discloses a photo-crosslinking gel technology, which includes o-nitrobenzyl optical trigger modified polyethylene glycol and its derivatives, double bond functional group modified polymer derivatives and light
  • the initiator is a technology for preparing hydrogel through photocrosslinking and gelation.
  • component B-photoinitiator is mainly used to improve the crosslinking speed and crosslinking efficiency of the original o-nitrobenzyl optical trigger (by generating extremely reactive nitrosose Free radicals for cross-linking), and the polymer derivatives cross-linked by photo-initiated free radical polymerization and polymer derivatives cross-linked by photo-coupling reaction can be mixed to form a composite photosensitive polymer solution, which can be activated under a single light
  • the initiator generates free radicals and carries out free radical cross-linking separately, and can also undergo photo-coupling reaction cross-linking and photo-induced nitroso cross-linking to realize multiple photo-cross-linking to prepare composite hydrogels.
  • the hydrogel material prepared by this technology has fast light curing speed, strong tissue adhesion, good biocompatibility, and good ductility and strength.
  • the present invention provides a photo-crosslinked hydrogel material with high strength and toughness, and a preparation method and application thereof.
  • high-strength and high-toughness hydrogels are prepared through photocrosslinking.
  • the cross-linking reaction between the polymer derivatives modified by the photosensitive molecular group connects the polymer skeletons through chemical bonds, which facilitates the transfer of force between the polymer skeletons, improves the mechanical properties of the hydrogel, and broadens the hydraulic setting The scope of application of glue.
  • the first object of the present invention is to provide a photosensitive polymer derivative modified by an o-nitrobenzyl optical trigger.
  • the photo-sensitive polymer derivative modified by the o-nitrobenzyl light trigger (ie component A) has the structure of formula I:
  • R' is selected from hydrogen, halogen atom, hydroxyl group, mercapto group, amine group, nitro group, cyano group, aldehyde group, ketone group, ester group, amide group, phosphonic acid group, phosphonate group, sulfonic acid group, sulfonic acid group Ester group, sulfone group, sulfoxide group, aryl group, heteroaryl group, alkyl group, alkylene group, modified alkyl group or modified alkylene group, etc.,
  • R" is selected from C, N, O or S;
  • R 1 is selected from hydrogen, ether bond substituents, ester bond substituents, carbonate bond substituents, urethane bond substituents, mercaptocarboxylate bond substituents or phosphate bond substituents Wait,
  • R 2 , R 3 , R 4 , R 5 are independently selected from hydrogen, halogen, hydroxyl, mercapto, amine, nitro, cyano, aldehyde, ketone, ester, amide, phosphonic acid, phosphine Ester group, sulfonic acid group, sulfonic acid ester group, sulfone group, sulfoxide group, aryl group, heteroaryl group, alkyl group, alkylene group, modified alkyl group or modified alkylene group, etc.;
  • P 1 is connected to any one or more of R 2 , R 3 , R 4 , and R 5 , and P 1 is not connected to R 1 .
  • R 1 can also be connected to a saturated or unsaturated alicyclic or alicyclic ring formed between R 2 , R 3 , R 4 , and R 5 , or an aromatic ring or aromatic heterocyclic ring formed.
  • R 1 and R 2 , R 3 , R 4 , and R 5 are connected to any one or more of the groups, or connected to the saturated or unsaturated lipid formed between R 2 , R 3 , R 4 , and R 5
  • the linking bond is selected from P 1 -O-, P 1 -S-, P 1 -NH-, P 1 -CH-, P 1 -COO -, P 1 -CONH-, one end of the link is connected to P 1 and the other end is connected to the benzene ring of the molecule represented by formula I.
  • P 1 is a hydrophilic or water-soluble multi-arm polyethylene glycol or its derivatives, and P 1 has the following general formula:
  • PEG in formula II is single-chain polyethylene glycol
  • X and Y are independently selected from polyethylene glycol, polypropylene glycol, polylactic acid, polyester, polyglycolic acid, polyvinyl alcohol, polyamino acid, polyacrylic acid, polymethacrylic acid, polyacrylamide, polymethacrylamide, Polyvinylpyrrolidone and copolymers of various hydrophilic monomers and hydrophilic monomers, hydrophilic monomers and hydrophobic monomers, hydrophobic monomers and hydrophobic monomers;
  • R 6 is a multi-arm branching center, and the degree of branching is 2-8.
  • the molecular weight of the structure connected to R 6 is not less than 6000, and R 6 is selected from one or two of the following structures A combination of the above:
  • the two-arm branch center includes the following structures:
  • the three-arm branch center includes the following structures:
  • the four-arm branch center includes the following structures:
  • the five-arm branch center includes the following structures:
  • the six-arm branching center includes the following structures:
  • the eight-arm branch center includes the following structures:
  • branch centers with the same number of arms can adopt commercial products or structures that can be simply aggregated.
  • P 1 is two-arm polyethylene glycol, three-arm polyethylene glycol, four-arm polyethylene glycol, six-arm polyethylene glycol or eight-arm polyethylene glycol.
  • P 1 is a two-arm polyethylene glycol with a molecular weight of 20,000 or more or a four-arm polyethylene glycol with a molecular weight of 40,000 or more.
  • n ⁇ 2 that is, the average number of o-nitrobenzyl optical triggers (that is, the structure in brackets in formula I) on a single P 1 polymer chain is greater than or equal to 2.
  • R 2 , R 3 , R 4 , and R 5 are connected to each other to form a saturated or unsaturated alicyclic or alicyclic heterocyclic ring together with carbon atoms, or form an aromatic ring or heteroaromatic ring. ring.
  • alkyl group is a saturated or unsaturated aliphatic linear or branched alkyl group having 1-30 carbon atoms;
  • the alkylene group is a saturated or unsaturated aliphatic linear or branched alkylene group having 1-30 carbon atoms;
  • Any carbon atoms of the modified alkyl group are selected from halogen atoms, -OH, -SH, -NO 2 , -CN, -CHO, -COOH, ester groups, amide groups, aryl groups, and arylene groups , -CO-, -O-, -S-, -SO-, -SO 2 -, primary amino group, secondary amino group, tertiary amino group, quaternary ammonium salt group, saturated or unsaturated monocyclic or bicyclic sub-ring A group obtained by replacing at least one of a hydrocarbyl group and a bridged aliphatic heterocycle.
  • the modified alkyl group has 1-30 atoms, and its carbon-carbon single bond can be arbitrarily replaced by a carbon-carbon double bond or a carbon-carbon triple bond. Key replacement
  • Any carbon atom of the modified alkylene group is selected from halogen atoms, -OH, -SH, -NO 2 , -CN, -CHO, -COOH, ester groups, amide groups, aryl groups, and alkylene groups.
  • the modified alkylene group has 1-30 atoms, and its carbon-carbon single bond can be arbitrarily replaced by a carbon-carbon double bond or Carbon-carbon triple bond replacement;
  • ether bond substituents are selected from the following structures:
  • ester bond substituents are selected from the following structures:
  • the carbonate bond substituents are selected from the following structures:
  • urethane bond substituents are selected from the following structures:
  • the mercaptocarboxylate bond substituents are selected from the following structures:
  • phosphate bond substituents are selected from the following structures:
  • the aryl group is a 5- to 10-membered aromatic monocyclic or aromatic condensed bicyclic structure
  • the heteroaryl group is a 5- to 10-membered aromatic monocyclic or aromatic fused bicyclic structure containing at least one heteroatom selected from O, S, N or Si on the ring;
  • the halogen atoms are each independently selected from F, Cl, Br, and I.
  • the alicyclic ring is a saturated or unsaturated 3-10 membered monocyclic or polycyclic alicyclic ring;
  • the alicyclic heterocyclic ring is a saturated or unsaturated 3-10 membered monocyclic or polycyclic aliphatic heterocyclic ring containing at least one heteroatom selected from O, S, N or Si on the ring.
  • S atom When it contains an S atom, it is optionally -S-, -SO- or -SO 2 -; the H on the alicyclic or alicyclic ring may optionally be substituted by a halogen atom, a nitro group, an aryl group, an alkyl group or Modified alkyl substitution;
  • the aromatic ring is a 5- to 10-membered aromatic monocyclic ring or aromatic fused bicyclic ring;
  • the aromatic heterocyclic ring is a 5- to 10-membered aromatic monocyclic or aromatic condensed bicyclic ring containing at least one heteroatom selected from O, S, N or Si; H on the aromatic ring or aromatic heterocyclic ring It may optionally be substituted by halogen atom, nitro group, aryl group, alkyl group or modified alkyl group.
  • alkyl substituents such as straight chain alkyl group-(CH 2 ) x CH 3 , branched chain alkyl group-(CH 2 ) x (CY'Y") y CH 3 (Y', Y" Is hydrogen, alkyl or modified alkyl), etc., where x and y are ⁇ 0 and are integers;
  • ether substituents such as -O(CH 2 ) x CH 3 , -O(CH 2 CH 2 O) x CH 3 , -O(CH 2 ) x (CH 2 CH 2 O) y CH 3 etc., where x and y ⁇ 0 and are integers;
  • the preferred structure of the thioether substituent such as -S(CH 2 ) x CH 3 , -S(CH 2 CH 2 O) x CH 3 , -S(CH 2 ) x (CH 2 CH 2 O) y CH 3 etc., where x and y ⁇ 0 and are integers;
  • amino group substituent such as -NH(CH 2 ) x CH 3 , -NH(CH 2 ) x (CY'Y”) y CH 3 , -N(CY'Y”) x (CY 'Y”) y , (Y', Y" are hydrogen, alkyl or modified alkyl), etc., where x and y are ⁇ 0 and are integers;
  • ester substituents such as -COO(CH 2 ) x CH 3 , -COO(CH 2 CH 2 O) x CH 3 , -COO(CH 2 ) x (CH 2 CH 2 O) y CH 3 etc., where x and y ⁇ 0 and are integers;
  • the preferred structure of the amide substituent such as -CONH(CH 2 ) x CH 3 , -CONH(CH 2 CH 2 O) x CH 3 , -CONH(CH 2 ) x (CH 2 CH 2 O) y CH 3 etc., where x and y ⁇ 0 and are integers;
  • alicyclic or alicyclic heterocyclic ring includes:
  • aromatic ring or aromatic heterocyclic ring includes:
  • R’ Some preferred structures of R’ include:
  • R 2 , R 3 , R 4 , R 5 include: -H, -OH, -SH, -NH 2 , -F, -Cl, -Br, -I, -CF 3 , -CCl 3 , -CBr 3, -CI 3, -NO 2 , -CN, -CHO, -COOH, -COONH 2, -SO 3 H and the like.
  • the formula I can be selected from the following structures in component A-1 to component A-30:
  • the second object of the present invention is to provide a photo-crosslinked hydrogel material with high strength and toughness.
  • the high-strength and tough photo-crosslinked hydrogel material is prepared from three components as raw materials, and the three raw materials are:
  • Photosensitive polymer derivative modified by o-nitrobenzyl light trigger referred to as component A;
  • component B Polymer derivatives modified with double bond functional groups, referred to as component B;
  • Photoinitiator referred to as component C.
  • the photocrosslinked hydrogel material of the present invention can also be referred to as a composite photocrosslinked hydrogel material.
  • component A is the photosensitive polymer derivative modified by the o-nitrobenzyl optical trigger provided in the first aspect of the present invention.
  • component B The polymer derivative modified with double bond functional group, referred to as component B, has the structure shown in formula III:
  • R 1 ', R 2 'and R 3 ' are independently selected from hydrogen, halogen atom, aromatic ring, heteroaromatic ring, alicyclic ring, alicyclic heterocyclic ring, alkyl group or modified alkyl group;
  • R 4 ' is selected From alkyl, ether bond substituents, ester bond substituents, carbonate bond substituents, amide bond substituents, urethane bond substituents, mercaptocarbonate bond substituents or phosphate esters Bond substituents;
  • n ⁇ 2 i.e. the average number of single P 1 'double bond functional groups on the polymer chain is greater than or equal to 2.
  • substituents, urethane bond substituents, mercaptocarboxylate bond substituents or phosphate bond substituents are the same as those of halogen atom, aromatic ring, heteroaromatic ring, alicyclic ring, and aliphatic heterocyclic ring in formula I , Alkyl groups, modified alkyl groups, ether bond substituents, ester bond substituents, carbonate bond substituents, amide bond substituents, urethane bond substituents, mercaptocarbonate bonds
  • Substituents or phosphate ester bond substituents have the same definition, except that in formula III, halogen atoms, aromatic rings, heteroaromatic rings, alicyclic rings,
  • P 1 ' is a hydrophilic or water-soluble natural polymer or synthetic polymer, or P 1 ' is independently selected from a variety of hydrophilic or water-soluble natural polymer or synthetic polymer, etc.;
  • the hydrophilic or water-soluble natural polymer includes natural polysaccharides and their modified or degraded products, proteins and their modified, modified and degraded polypeptides, etc.;
  • the natural polysaccharide substances include hyaluronic acid, carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, alginic acid, dextran, agarose, heparin, chondroitin sulfate , Ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan or chitosan quaternary ammonium salt;
  • the protein includes various hydrophilic or water-soluble animal and plant proteins, collagen, serum protein, silk fibroin, and elastin, and the protein degradation product includes gelatin or polypeptide;
  • Hydrophilic or water-soluble synthetic polymers include two-arm or multi-arm polyethylene glycol, polyethyleneimine, dendrimers, synthetic peptides, polyamino acids, polyacrylic acid, polymethacrylic acid, polyacrylamide, and polymethacrylic acid Hydrophilic or water-soluble copolymers of amide, polyvinyl alcohol, polyvinylpyrrolidone, and various hydrophilic monomers and hydrophilic monomers, and hydrophilic monomers and hydrophobic monomers.
  • P 1 ' is selected from hyaluronic acid, carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, alginic acid, dextran, agarose, heparin, cartilage sulfate Chitosan, ethylene glycol chitosan, propylene glycol chitosan, chitosan lactate, carboxymethyl chitosan, chitosan quaternary ammonium salt.
  • polymer derivative modified by the double bond functional group of formula III can be selected from the following structures in component B-1 to component B-8:
  • the photoinitiator is a substance capable of generating free radicals under light.
  • component C is a water-soluble photoinitiator or a photoinitiator that can be dispersed in water;
  • component C is LAP (component C-1), I 2959 (component C-2), Eosin-Y (component C-3), benzophenone (component C-4), Na-TPO (component C-5), etc. and its derivatives;
  • component C is LAP, Na-TPO and their derivatives
  • the third objective of the present invention is to provide a method for preparing the high-strength and tough photo-crosslinked hydrogel material.
  • the preparation method of the high-strength and tough photo-crosslinked hydrogel material includes the following steps:
  • Component A, component B and component C are dissolved in a biocompatible medium to obtain a hydrogel precursor solution;
  • the hydrogel precursor solution undergoes photocrosslinking to form a hydrogel.
  • Method 1 Dissolve component A in a biocompatible medium to obtain solution A; dissolve component B in a biocompatible medium to obtain solution B; dissolve component C in a biocompatible medium to obtain solution C; A, Solution B and Solution C are mixed uniformly to obtain a hydrogel precursor solution.
  • Method 2 Mix component A, component B and component C and dissolve in a biocompatible medium to obtain a hydrogel precursor solution.
  • the biocompatible medium is selected from distilled water, physiological saline, buffer, decellularized matrix, or cell culture medium solution. According to different applications, different media can be selected.
  • the concentration of component A is 0.1% to 60% by weight, preferably 1% to 40% by weight
  • the concentration of component B is 0.01% wt-20% wt, preferably 0.05% wt-10% wt
  • the concentration of component C is 0.01% wt-5% wt, preferably 0.1% wt-3% wt
  • the total polymer concentration is 0.1% wt -60%wt, preferably 1%wt-10%wt.
  • the wavelength of the light source is determined according to the absorption wavelength of the o-nitrobenzyl light trigger and the photoinitiator, and can be 250-500nm, preferably 300-450nm, more preferably 365, 375, 385 , 395, 405nm.
  • the technical principle of the photo-crosslinking of the hydrogel precursor solution under the irradiation of a light source is: the o-nitrobenzyl optical trigger in component A and the component C-photoinitiator undergo a free radical reaction under illumination, At the same time, the double bond functional group in component B and the component C-photoinitiator undergo free radical polymerization under light, and the free radicals generated by the two reactions further react and crosslink to form a hydrogel.
  • the photocrosslinked hydrogel material provided by the present invention is mainly characterized by: component A (photosensitive polymer derivative modified by o-nitrobenzyl light trigger) and component B (polymer derivative modified by double bond functional group) )
  • component A photosensitive polymer derivative modified by o-nitrobenzyl light trigger
  • component B polymer derivative modified by double bond functional group
  • component C photoinitiator
  • the present invention increases the strength and/or toughness of this type of hydrogel by an order of magnitude or even higher, solves the bottleneck problem of poor mechanical properties of the current hydrogel, and broadens the application range of the hydrogel.
  • the fourth objective of the present invention is to provide a kit for preparing the high-strength and tough photo-crosslinked hydrogel material of the present invention.
  • the kit contains: component A-photosensitive polymer derivative modified with o-nitrobenzyl light trigger; component B-polymer derivative modified with double bond functional group, component C-photoinitiator and related water Instructions for gel preparation and application.
  • biocompatible media such as distilled water, physiological saline, buffer and cell culture medium can also be included.
  • the application of the hydrogel described in the instructions in the above kit includes its postoperative wound closure, interstitial fluid leakage plugging, hemostatic materials, tissue engineering scaffold materials, 3D printed bio-inks and as cells, proteins or drug carriers On the application.
  • the fifth object of the present invention is to provide the application of the high-strength and tough photo-crosslinked hydrogel material.
  • the present invention provides the application of the high-strength and tough photo-crosslinked hydrogel material as a material or medicine for preparing postoperative wound closure-tissue suture-free materials.
  • the present invention provides the application of the high-strength and tough photo-crosslinked hydrogel material as a post-operative wound closure-tissue repair material or medicine.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a post-operative wound closure-postoperative anti-adhesion material or medicine.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a material or medicine for preparing postoperative wound closure-oral ulcers.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a material or medicine for preparing interstitial fluid leakage blocking-intestinal leakage blocking material.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a material or medicine for preparing tissue fluid leakage plugging-cerebrospinal fluid plugging.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a material or medicine for preparing tissue fluid leakage sealing-gastric leakage sealing material.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a hemostatic material-hepatic hemostatic material or medicine.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a hemostatic material-kidney hemostatic material or medicine.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a hemostatic material-spleen hemostatic material or medicine.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a hemostatic material-pancreatic hemostatic material or medicine.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a hemostatic material-bone section hemostatic material or medicine.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a hemostatic material-arterial hemostatic material or medicine.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a hemostatic material-cardiac hemostatic material or medicine.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as an adhesive material-patch fixing material.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as an adhesive material-valve fixing material.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as an adhesive material-mucosal fixing material.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as an adhesive material-tissue fixing material.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as an adhesive material-bone fixing material.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a tissue reinforcement material-patch material.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a tissue engineering scaffold material-cartilage repair material or medicine.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a tissue engineering scaffold material-bone repair material or medicine.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a tissue engineering scaffold material-bone/cartilage composite defect repair material or medicine.
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material in 3D printing (FDM) material-bio-ink.
  • FDM 3D printing
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material in 3D printing (SLA) material-biological ink.
  • SLA 3D printing
  • the present invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material in 3D printing (DLP) material-biological ink.
  • DLP 3D printing
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material in 3D printing-combined interventional surgery.
  • the invention also provides the application of the high-strength and tough photo-crosslinked hydrogel material as a carrier for preparing cells, proteins, and drugs.
  • the present invention controls the average arm length of polyethylene glycol and its derivatives in component A, and the molar ratio of o-nitrobenzyl optical trigger to polyethylene glycol and its derivatives, so as to realize the properties of hydrogel.
  • the strength and/or toughness of the hydrogel prepared by the present invention has been improved by an order of magnitude or even higher (specific data such as Examples 19-22), which solves the current problem of water
  • the bottleneck problem of poor mechanical properties of the gel broadens the application range of hydrogels.
  • the present invention retains the technical advantages of hydrogel preparation technology such as fast curing speed, strong tissue adhesion, and good biocompatibility. Therefore, compared with the prior art, the present invention has the following advantages and beneficial effects:
  • the tissue has strong adhesion and can gel in situ on the surface of the tissue.
  • the aldehyde/ketone and nitroso groups generated by the light can react with the sulfhydryl, amine and carboxyl groups on the surface of the tissue to realize hydrogel
  • the integration of chemical bonds with surrounding tissues overcomes the problem of free radical polymerization and cross-linking that requires additional primers;
  • the raw materials are mainly derived from natural polymer materials, and the formed hydrogel is degradable;
  • the light curing speed is fast, and the gel point can be reached within 10s, and the final modulus can be reached within 20s;
  • the hydrogel precursor solution can be smeared or sprayed on the surface of the tissue during use, and it can be quickly integrated with the tissue under light without primer.
  • the tissue surface is glued in situ.
  • Figure 1 shows the hydrogel precursor solution (30% component A-25/5% component B-1/1% component C-1), (4% component A-15/3% component B- 1/0.2% component C-1), (30% 4APEG50/5% component B-1/2% component C-1) and (4% 4APEG50/3% component B-1/0.2% component C-1) Real-time rheological graph of gel formation under light.
  • Figure 2 shows the hydrogel (30% component A-25/5% component B-1/1% component C-1), (4% component A-15/3% component B-1/0.2 % Component C-1), (30% 4APEG50/5% component B-1/2% component C-1) and (4% 4APEG50/3% component B-1/0.2% component C-1 ) The compressive stress-strain curve.
  • Figure 3 shows the hydrogel (30% component A-25/5% component B-1/1% component C-1), (4% component A-15/3% component B-1/0.2 % Component C-1), (30% 4APEG50/5% component B-1/2% component C-1) and (4% 4APEG50/3% component B-1/0.2% component C-1 ) The tensile stress-strain curve.
  • Figure 4 is a visual diagram of the wound closure-tissue-free suture effect of hydrogel (4% component A-15/3% component B-1/0.2% component C-1).
  • Figure 5 is a visual diagram of the effect of hydrogel (4% component A-15/3% component B-1/0.2% component C-1) on wound closure and skin repair.
  • Figure 6 is a visual diagram of the effect of hydrogel (3% component A-22/2% component B-1/0.2% component C-1) on wound closure-promoting repair after cervical resection.
  • Figure 7 is a visual diagram of the effect of hydrogel (3% component A-12/2% component B-1/0.2% component C-1) on wound closure-promoting repair after hemorrhoidectomy.
  • Figure 8 is a visual diagram of the effect of hydrogel (4% component A-15/3% component B-1/0.2% component C-1) on wound closure-anti-adhesion after abdominal cavity operation.
  • Figure 9 is a visual diagram of the effect of hydrogel (4% component A-15/3% component B-1/0.2% component C-1) on wound closure and anti-adhesion after vocal cord surgery.
  • Figure 10 is a visual diagram of the effect of hydrogel (4% component A-15/3% component B-1/0.2% component C-1) on wound closure-oral ulcers.
  • Figure 11 is a visual diagram of the effect of hydrogel (4% component A-15/3% component B-1/0.2% component C-1) as a hemostatic material-liver hemostasis.
  • Figure 12 is a visual diagram of the effect of hydrogel (3% component A-22/2% component B-1/0.2% component C-5) as a hemostatic material-kidney hemostasis.
  • Figure 13 is a visual diagram of the effect of the hydrogel (3% component A-12/2% component B-1/0.2% component C-1) as a hemostatic material-cardiac hemostasis.
  • Figure 14 is a visual diagram of the effect of hydrogel (4% component A-15/3% component B-1/0.2% component C-1) as a hernia patch fixing material.
  • Figure 15 is a visual diagram of the effect of hydrogel (30% component A-26/5% component B-1/1% component C-1) as a heart patch.
  • Figure 16 is a visual diagram of the 3D printing (DLP) effect of a hydrogel (30% component A-25/5% component B-1/1% component C-1) as a biological ink.
  • DLP 3D printing
  • component A-2 dissolve polyethylene glycol (8g) in anhydrous CH 2 Cl 2 (100mL), add 4-dimethylaminopyridine (DAMP; 0.005g) and triethylamine (0.101g), the above-mentioned mixed solution was added dropwise to a solution of 4-nitrophenyl chloroformate (0.201g) in anhydrous CH 2 Cl 2 (3 mL). The solution was stirred at room temperature for 5 hours. The solvent was removed under reduced pressure until the solvent was about half of the original volume, the reaction system was poured into Et 2 O, and the white solid obtained was collected by filtration. Repeat the above heavy weighting process to completely remove the unreacted 4-nitrochlorophenyl chloroformate, etc.
  • DAMP 4-dimethylaminopyridine
  • Synthesis of component A-22 refer to the synthesis method of component A-2.
  • the labeling rate (3.4-3.6) was determined by 1 H NMR spectroscopy.
  • Synthesis of component A-23 refer to the synthesis method of component A-2.
  • the labeling rate (3.4-3.6) was determined by 1 H NMR spectroscopy.
  • Synthesis of PEG100 Refer to the synthesis method of component A-2. The labeling rate (3.4-3.6) was determined by 1 H NMR spectroscopy. 1 H NMR (400MHz, D 2 O): ⁇ 3.72 (s, 900H), 7.33 (s, 2H), 7.81 (s, 2H), 4.96 (s, 4H).
  • Synthesis of 4APEG25 Refer to the synthesis method of component A-2. The labeling rate (3.4-3.6) was determined by 1 H NMR spectroscopy. 1 H NMR (400MHz, D 2 O): ⁇ 3.72 (s, 450H), 7.33 (s, 4H), 7.81 (s, 4H), 4.96 (s, 8H).
  • Synthesis of 4APEG50 Refer to the synthesis method of component A-2. The labeling rate (3.4-3.6) was determined by 1 H NMR spectroscopy. 1 H NMR (400MHz, D 2 O): ⁇ 3.72 (s, 900H), 7.33 (s, 4H), 7.81 (s, 4H), 4.96 (s, 8H).
  • Rheological analysis adopts HAAKE MARS rheometer, the test platform at 37°C Perform rheological tests on the above.
  • the effects of UV light time, light intensity and the mass concentration of polymer derivatives on the gel time and storage modulus of hydrogels were studied.
  • Figure 1 The experimental group hydrogel precursor solution (30% component A-25/5% component B-1/1% component C-1) and hydrogel precursor solution (4% component A-15 /3% component B-1/0.2% component C-1), and the control hydrogel precursor solution (30% 4APEG50/5% component B-1/2% component C-1) and water Real-time rheogram of gel precursor solution (4% 4APEG50/3% component B-1/0.2% component C-1) under light irradiation (in the rheological test, G'is the storage modulus, G" It is the loss modulus, when G'exceeds G", it is the gel point).
  • Hydrogel material composition Glue point(s) Gel strength (Pa) Component A-4/component B-1/component C-1 (30% wt: 5% wt: 1% wt) 2 ⁇ 5 113,000 Component A-5/component B-1/component C-2 (30% wt: 5% wt: 1% wt) 2 ⁇ 5 115,000 Component A-7/component B-1/component C-5 (30% wt: 5% wt: 2% wt) 2 ⁇ 5 102,000 Component A-10/component B-1/component C-1 (30% wt: 5% wt: 2% wt) 2 ⁇ 5 114,500 Component A-11/component B-1/component C-1 (30% wt: 5% wt: 2% wt) 2 ⁇ 5 106,200 Component A-12/component B-1/component C-5 (30% wt: 5% wt: 2% wt) 2 ⁇ 5 111,050 Component A-13/component B
  • Component A-23/component B-1/component C-5 (30% wt: 5% wt: 2% wt) 2 ⁇ 5 104,500 Component A-25/component B-1/component C-1 (30% wt: 5% wt: 1% wt) 2 ⁇ 5 116,400 Component A-26/component B-1/component C-1 (30% wt: 5% wt: 1% wt) 2 ⁇ 5 115,500 Component A-29/component B-1/component C-5 (30% wt: 5% wt: 2% wt) 2 ⁇ 5 110,100 Component A-4/component B-2/component C-1 (30% wt: 5% wt: 1% wt) 2 ⁇ 5 110,030 Component A-5/component B-3/component C-2 (30% wt: 5% wt: 1% wt) 2 ⁇ 5 119,000 Component A-7/component B-4/component C-5 (30% wt:
  • PEG50/component B-1/component C-1 (3% wt: 2% wt: 0.2% wt) 2 ⁇ 5 1,050 PEG100/component B-1/component C-1 (4% wt: 3% wt: 0.2% wt) 2 ⁇ 5 1,520 PEG100/component B-1/component C-1 (3% wt: 2% wt: 0.2% wt) 2 ⁇ 5 940 4APEG25/component B-1/component C-1 (4% wt: 3% wt: 0.2% wt) 2 ⁇ 5 1,500 4APEG25/component B-1/component C-1 (3% wt: 2% wt: 0.2% wt) 2 ⁇ 5 1,300 4APEG50/component B-1/component C-1 (4% wt: 3% wt: 0.2% wt) 2 ⁇ 5 4,500 4APEG50/component B-1/component C-1 (3% wt: 2% wt: 0.2% wt) 2 ⁇
  • the compression performance test adopts the GT-TCS-2000 tensile machine, and the compression test sample is a cylindrical sample with a diameter of 10mm and a height of 3mm, and the test speed is 1mm/min.
  • Figure 2 shows the experimental group of hydrogels (30% component A-25/5% component B-1/1% component C-1) and hydrogel (4% component A-15/3% component B-1/0.2% component C-1), as well as the control hydrogel (30% 4APEG50/5% component B-1/2% component C-1) and hydrogel (4% 4APEG50/3 % Component B-1/0.2% component C-1) compression performance.
  • the compressive strength of the hydrogel in the experimental group was 6.7 times and 5.5 times that of the control group, respectively, indicating that the compressive strength of the hydrogel in the experimental group was significantly higher than that of the control group regardless of high-quality concentration or low-quality concentration.
  • the compressive strength of other hydrogels with different ratios is also significantly higher than that of the control group.
  • the specific data are shown in Table 3.
  • Hydrogel material composition Compressive strength (MPa) Component A-4/component B-1/component C-1 (30% wt: 5% wt: 1% wt) 30.9 Component A-5/component B-1/component C-2 (30% wt: 5% wt: 1% wt) 32.4 Component A-7/component B-1/component C-5 (30% wt: 5% wt: 2% wt) 35.3 Component A-10/component B-1/component C-1 (30% wt: 5% wt: 2% wt) 35.9 Component A-11/component B-1/component C-1 (30% wt: 5% wt: 2% wt) 36.2 Component A-12/component B-1/component C-5 (30% wt: 5% wt: 2% wt) 31.4 Component A-13/component B-1/component C-1 (30% wt: 5% wt: 2% wt) 35.9 Component A
  • Component A-4/component B-2/component C-1 (30% wt: 5% wt: 1% wt) 34.8 Component A-5/component B-3/component C-2 (30% wt: 5% wt: 1% wt) 33.8 Component A-7/component B-4/component C-5 (30% wt: 5% wt: 2% wt) 31.5 Component A-10/component B-5/component C-1 (30% wt: 5% wt: 2% wt) 34.9 Component A-11/component B-6/component C-2 (30% wt: 5% wt: 2% wt) 34.2 Component A-12/component B-2/component C-5 (30% wt: 5% wt: 2% wt) 32.8 Component A-13/component B-3/component C-1 (30% wt: 5% wt: 2% wt) 33.5 Component A-15/component B-4/component C-2 (30%
  • Example 21 Test of tensile properties of photo-crosslinked hydrogel
  • the tensile performance test uses a GT-TCS-2000 tensile machine.
  • the tensile test sample is a dumbbell-shaped specimen with a length of 20 mm, a width of 3 mm, and a thickness of 2 mm.
  • the test speed is 5 mm/min.
  • Figure 3 shows the experimental group of hydrogels (30% component A-25/5% component B-1/1% component C-1) and hydrogel (4% component A-15/3% component B-1/0.2% component C-1), as well as the control hydrogel (30% 4APEG50/5% component B-1/2% component C-1) and hydrogel (4% 4APEG50/3 % Component B-1/0.2% component C-1) tensile properties.
  • the tensile strength of the hydrogel in the experimental group was 8 and 3 times that of the control group, respectively, indicating that the tensile strength of the hydrogel in the experimental group was significantly higher than that of the control group regardless of high-quality concentration or low-quality concentration.
  • the tensile strength of other hydrogels with different ratios is also significantly higher than that of the control group.
  • the specific data are shown in Table 4.
  • Component A-11/component B-6/component C-2 (30% wt: 5% wt: 2% wt) 11.1
  • Component A-12/component B-2/component C-5 (30% wt: 5% wt: 2% wt) 12.6
  • Component A-13/component B-3/component C-1 (30% wt: 5% wt: 2% wt) 13.2
  • Component A-15/component B-4/component C-2 (30% wt: 5% wt: 2% wt) 10.7
  • Component A-16/component B-5/component C-5 (30% wt: 5% wt: 2% wt) 11.9
  • Component A-21/component B-6/component C-1 (30% wt: 5% wt: 2% wt) 10.8
  • Component A-22/component B-2/component C-2 (30% wt: 5% wt: 2% wt) 12.6
  • the stress-strain curve of the hydrogel is obtained through the tensile test, and the toughness (work of fracture) (MJ m -3 ) is calculated from the integral area under the tensile stress-strain curve.
  • the tensile performance test uses a GT-TCS-2000 tensile machine.
  • the tensile test sample is a dumbbell-shaped specimen with a length of 20 mm, a width of 3 mm, and a thickness of 2 mm.
  • the test speed is 5 mm/min.
  • Table 5 shows the experimental group of hydrogels (30% component A-25/5% component B-1/1% component C-1) and hydrogel (4% component A-15/3% component B-1/0.2% component C-1), and the control hydrogel (30% 4APEG50/5% component B-1/2% component C-1) and hydrogel (4% 4APEG50/3 % Component B-1/0.2% component C-1) toughness.
  • Component A-15/component B-4/component C-2 (30% wt: 5% wt: 2% wt) 10.2
  • Component A-16/component B-5/component C-5 (30% wt: 5% wt: 2% wt) 10.8
  • Component A-21/component B-6/component C-1 (30% wt: 5% wt: 2% wt) 9.8
  • Component A-22/component B-2/component C-2 (30% wt: 5% wt: 2% wt) 9.6
  • Component A-23/component B-3/component C-5 (30% wt: 5% wt: 2% wt) 10.5
  • Component A-25/component B-4/component C-1 (30% wt: 5% wt: 1% wt) 11.2
  • Component A-26/component B-5/component C-2 (30% wt: 5% wt: 1% wt) 11.4
  • hydrogel systems composed of different materials can also be applied to wound closure-tissue-free suture.
  • hydrogel systems composed of different materials can also be used for wound closure and skin repair.
  • Example 25 Application of photo-crosslinked hydrogel to wound closure-promoting repair after cervical resection
  • the cervix of female New Zealand white rabbits was wounded with an electric knife. Divide the two cervix into two groups for treatment. One group is to apply the hydrogel precursor solution (3% component A-22/2% component B-1/0.2% component C-1) to the wound site, and then, under 395nm LED light source, the The hydrogel precursor solution is completely solidified into a hydrogel, realizing the sealing of the wound surface. No processing is done on the other side. Observe the repair effect of the cervix within 7 days. As shown in the figure, the left cervix is the hydrogel group, and the right cervix is the blank group. The photocrosslinked hydrogel wound repair rate is significantly faster than that of the blank group. The wound has healed completely, but the blank group still has Hyperemia ( Figure 6).
  • hydrogel systems composed of different materials can also be used for wound closure-promoting repair after cervical resection.
  • Example 26 Application of photo-crosslinked hydrogel to wound closure-promoting repair after hemorrhoidectomy
  • hydrogel systems composed of different materials can also be used for wound closure-promoting repair after hemorrhoidectomy.
  • Example 27 Application of photo-crosslinked hydrogel to wound closure-anti-adhesion after abdominal cavity operation
  • the obtained hydrogel was fixed on the wound site, and the hydrogel could not be peeled off from the wound site when a certain force was applied to it with a surgical blade.
  • the above process from the administration of the hydrogel precursor solution to the complete gelation can be completed within 1 min.
  • the SD rats were reared in a sterile environment for 14 days. After 14 days, the abdominal cavity of SD rats was opened again, and their abdominal adhesion was recorded (Figure 8, where a is the control group and b is the experimental group).
  • hydrogel systems composed of different materials can also be used for wound closure-anti-adhesion after abdominal cavity surgery.
  • Example 28 Application of photo-crosslinked hydrogel to wound closure-anti-adhesion after vocal cord surgery
  • tissue sections of the wound in the experimental group and the control group were analyzed histologically by H&E staining.
  • Beagle dogs in the experimental group had almost completely recovered from the damage to their vocal cords, and the surface layer had been re-epithelialized.
  • the fibroblasts and inflammatory cells in the vocal cords of beagle dogs in the control group were deposited at the adhesion sites.
  • hydrogel systems composed of different materials can also be used for wound closure-anti-adhesion after vocal cord surgery.
  • an oral ulcer with a diameter of 1.0 cm was constructed in the oral cavity of SD rats. Then 200 ⁇ L of the hydrogel precursor solution (4% component A-15/3% component B-1/0.2% component C-1) was filled into the wound site. Due to the good fluidity of the solution, the wound can be fully filled and penetrated by the hydrogel precursor solution. Then, under the irradiation of a 395nm LED light source, the hydrogel was prepared in situ on the oral cavity defect to achieve the sealing of the oral wound. Next, compare the repair effects of the in-situ formed hydrogel and the oral wounds of SD rats that were only cleaned with saline in 5 days. The tissue sections of the wounds in the experimental group and the control group were stained by H&E.
  • the histological analysis was performed (Figure 10).
  • the wound repair rate of the hydrogel formed in situ was significantly faster than that of the control group, and the mucosa basically returned to normal level at 5 days; the wound repair rate without hydrogel filling was significantly slower, indicating that the photocrosslinked hydrogel is used as a cell scaffold
  • the material promotes the repair of oral ulcers.
  • hydrogel systems composed of different materials can also be applied to wound closure-oral ulcers.
  • New Zealand male white rabbits were divided into two groups for cecal leakage sealing experiment: a: Hydrogel treatment (4% component A-15/3% component B-1/0.2% component C-1) group ; B: Control group without treatment.
  • a leaky model was made in the rabbit's cecum, and then the hydrogel precursor solution was applied to the wound. After it was fully penetrated, the gel was formed in situ by light. After the gel was formed, the hydrogel could firmly adhere to the defect. No additional fixation is required.
  • the rabbits in the experiment were killed by intravenous air injection, and the cecum was extracted to evaluate the experimental repair effect. The results showed that the cecum sealed with hydrogel did not leak, while the cecum that was not treated with hydrogel suffered serious leakage. After several weeks of repair, the original defect of the cecum has been significantly repaired after hydrogel treatment. Therefore, the hydrogel can not only effectively block leakage, but also help repair damaged tissues after surgery.
  • hydrogel systems composed of different materials can also be used for exudate sealing-intestinal leak sealing.
  • a Hydrogel treatment (4% component A-15/3% component B-1/0.2% component C-1) group
  • b Control group without treatment
  • c Suture with 3-0 surgical sutures.
  • a model of the wound was made in the stomach of the rat, and then the hydrogel precursor solution was applied to the wound. After it was fully penetrated, the gel was formed in situ with light. After the gel was formed, the hydrogel could firmly adhere to the defect. No additional fixation is required.
  • the suture group was sutured with 3-0 surgical suture. Ten days after the operation, the SD rats were euthanized, and the stomach was extracted to evaluate the experimental results.
  • hydrogel systems composed of different materials can also be used for tissue exudate sealing-gastric leak sealing.
  • SD rats were used to evaluate the hemostatic effect of the hydrogel and were divided into two groups for hepatic hemostatic experiments: a: hydrogel treatment (4% component A-15/3% component B-1/0.2% group Divided into C-1) group; b blank control group.
  • the experimental rats were anesthetized by intraperitoneal injection of chloral hydrate (4% aqueous solution) with an injection volume of 0.9ml/100g. After deep anesthesia, the rat's anterior chest hair was shaved with a shaver and disinfected with iodine. Then make an incision about 4 cm long along the midline of the abdominal cavity to open the abdominal cavity and expose the liver. Make a 2cm incision in the left lobe of the liver.
  • hydrogel precursor solution was added to the incision to cover the cut surface, and 395nm LED light was used for 1 min to gel to stop bleeding; group b did not do any treatment, let the blood from the liver incision coagulate naturally, absorb the blood with gauze, and record the bleeding by weight loss method Volume, and bleeding time ( Figure 11).
  • the hydrogel of group a was cross-linked in situ at the incision and the cut surface wound was isolated, the liver was put back into the abdominal cavity and sutured. Group b was sutured directly without treatment. After 14 days, observe the recovery of the liver of SD rats. The rats were killed by intraperitoneal injection of an overdose of anesthetic chloral hydrate (4% aqueous solution, 2.7ml/100g).
  • the abdominal cavity was opened along the midline of the thoracic cavity, and the liver recovery of the three groups of rats was observed and photographed. record.
  • the tissues of the liver injury were sampled, and the specimens were fixed with 4% formalin solution for 2 days. After dehydration treatment, they were embedded in paraffin, and the tissue sectioning operation was performed with a microtome. The thickness of the specimen was 5 ⁇ m.
  • the specimens were stained with H&E, and photographed with an optical microscope to observe and record.
  • the experimental results showed that the liver of group a recovered well, the hydrogel was completely degraded, no adhesions occurred, and new liver tissue grew from the liver incision. The adhesion between the liver and the omentum is common in group b.
  • H&E staining showed that the surface of the liver in the experimental group was smooth and round, with abundant blood vessel distribution, and the liver interface was clear. H&E staining of the adhered liver revealed that the liver interface was uneven, the liver and omentum tissue were adhered together, and there were inflammatory cells deposited at the interface.
  • hydrogel systems composed of different materials can also be applied to the hemostatic material-liver hemostasis.
  • New Zealand white rabbits were used to evaluate the hemostatic effect of the hydrogel and divided into two groups for renal hemostatic experiments: a: Hydrogel treatment (3% component A-22/2% component B-1/0.2% group Divided into C-5) group; b blank control group.
  • the side abdomen of the New Zealand white rabbits were shaved with a hair shaver and disinfected with iodine. Then make an incision about 5 cm long along the side abdomen to open the abdominal cavity and expose the kidneys. Make a circular injury incision with a diameter of about 1 cm and a depth of about 3 mm in the kidney.
  • hydrogel systems composed of different materials can also be applied to the hemostatic material-kidney hemostasis.
  • Beagle dogs were used to evaluate the hemostatic effect of the hydrogel and divided into three groups for spleen hemostasis experiment: a: gelatin sponge group; b: hydrogel treatment ((4% component A-15/3% component B-1/0.2% component C-1)) group; c positive control group.
  • the experimental beagles were anesthetized by intramuscular injection of barbiturate anesthetics at 0.5ml/kg. After deep anesthesia, the beagles’ lateral abdominal hair was shaved with a shaver and disinfected with iodine. Then make an incision about 10 cm long along the side abdomen to open the abdominal cavity and expose the spleen. Make an 8mm diameter incision in the spleen.
  • group a gelatin sponge was used for hemostasis; in group b, a hydrogel precursor solution was added to the incision to cover the cut surface, and 395nm LED light was used for 1 min to gel to stop bleeding; in group c, no treatment was performed to allow the spleen wound to coagulate naturally, and use gauze to absorb it. Blood, record the amount of bleeding and bleeding time by weight loss method. After the experiment, group a left the gelatin sponge adhered to the cut surface together in the beagle dog for suture. In group b, the hydrogel was cross-linked in situ at the incision and the cut surface wound was isolated. The spleen was put back into the abdominal cavity and sutured. Group c was sutured directly without treatment.
  • the beagle was killed by intramuscular injection of overdose anesthetic barbiturate anesthetics.
  • the abdominal cavity was opened along the side of the abdominal cavity to observe the recovery of the spleen of the three groups of beagles, and take pictures to record.
  • the tissues of the injured part of the spleen were sampled, the specimens were fixed with 4% formalin solution for 2 days, dehydrated, embedded in paraffin, and sliced with a microtome. The thickness of the specimen was 5 ⁇ m. Finally, the specimens were stained with H&E, and photographed with an optical microscope to observe and record.
  • hydrogel systems composed of different materials can also be applied to the hemostatic material-spleen hemostasis.
  • a Hydrogel treatment (4% component A-15/3% component B-1/0.2% component C-1) group
  • b Bone wax treatment group
  • c control group without treatment.
  • a bone cross-section hemorrhage model was made in the rabbit femur.
  • Group a was to apply the hydrogel precursor solution to the wound. After it was fully penetrated, the light was used to form a gel in situ to effectively block the bone cross-section hemorrhage.
  • the gel's excellent tissue adhesion and light curing speed can play a timely and effective hemostasis effect;
  • group b uses conventional bone wax to treat bleeding wounds; group c does not treat bleeding wounds.
  • the rabbits in the experiment were sacrificed by intravenous air injection, and samples were taken to evaluate the effect of the experimental repair.
  • the results show that the wound treated with hydrogel has a better hemostatic effect, which is basically the same as that of the bone wax group, while the wound without treatment will have continuous bleeding.
  • the original wound bleeding site was treated with hydrogel and the tissue was obviously repaired, but the wound treated with bone wax was not repaired, mainly because the bone wax did not degrade in the body, therefore, the hydrogel Not only can effectively realize the hemostasis of the bone section, but also help repair the damaged tissue after the operation.
  • hydrogel systems composed of different materials can also be applied to the hemostatic material-bone cross-section hemostasis.
  • Example 36 Application of photo-crosslinked hydrogel to hemostatic material-cardiac hemostasis
  • a hydrogel treatment (3% component A-12/2% component B-1/0.2% component C-1) group
  • b fibrinogen glue treatment group
  • C Control group without treatment.
  • group a the hydrogel precursor solution is applied to the wound, and the gel is formed in situ with 395nm light to achieve effective blocking of heart bleeding. Due to the excellent tissue adhesion and light curing speed of the hydrogel, it can Play a timely and effective hemostasis effect; group b uses fibrinogen glue to treat bleeding wounds; group c does not treat bleeding wounds.
  • the latter two groups were unable to achieve the hemostatic effect of pulmonary artery bleeding due to poor adhesion of the hemostatic material and insufficient strength of the glue itself.
  • the photo-crosslinked hydrogel group can quickly stop heart bleeding because of its excellent tissue adhesion and strength (Figure 13).
  • hydrogel systems composed of different materials can also be applied to hemostatic materials-cardiac hemostasis.
  • SD rats were divided into two groups for hernia patch fixation experiment: a: Hydrogel fixation (hydrogel (4% component A-15/3% component B-1/0.2% component C-1) ) Group; b: suture group.
  • a Hydrogel fixation (hydrogel (4% component A-15/3% component B-1/0.2% component C-1) ) Group
  • b suture group.
  • group a a hydrogel precursor solution was applied to the patch, and the light was fully penetrated to form a gel in situ.
  • the effect of fixation patch; group b uses suture method to fix the patch.
  • Two weeks after the operation the rats were killed by intraperitoneal injection of anesthetic, and samples were taken to evaluate the experimental repair effect (Figure 14 left group b, right side To go to group a).
  • the results show that the patch fixed with hydrogel is well fixed, and a film is formed at the contact position between the patch and the tissue, and the patch is wrapped in it.
  • hydrogel systems composed of different materials can also be used for the fixation of hernia patches.
  • Example 38 Application of photocrosslinked hydrogel to fixation of conjunctival flap after pterygium surgery
  • New Zealand male white rabbits were divided into two groups for the fixation experiment of conjunctival flap after pterygium surgery: a: Hydrogel fixation (3% component A-12/2% component B-1/0.2% component C -1) group; b: suture group.
  • a conjunctival flap was removed from the rabbit's eye.
  • group a the hydrogel precursor solution was applied to the wound, and after it was fully penetrated, the conjunctival flap was covered and lighted to form a glue in situ to realize the fixed bonding of the conjunctival flap;
  • group b the conjunctival flap was fixed with sutures.
  • hydrogel systems composed of different materials can also be used to fix the conjunctival flap after pterygium surgery.
  • mice were divided into two groups to test the heart patch.
  • Group a is the myocardial infarction model group
  • group b is the hydrogel patch (30% component A-26/5% component B-1/1% component C-1) group.
  • the mice were anesthetized with pentobarbital sodium (60mg/kg), and the small animal laryngoscope was used to intubate the oral cavity, and then the small animal ventilator (Shenzhen Reward, 407) was used for positive pressure ventilation with a respiratory rate of 70 times. /Min, the tidal volume is 2.5ml/time. Use limb leads for ECG monitoring.
  • the rats in the sham myocardial infarction group were subjected to the same procedure, only threading the coronary arteries without ligating. Put the heart into the chest cavity and suture layer by layer.
  • One month after operation hematoxylin-eosin and Masson trichrome staining were used to evaluate the ventricular remodeling after myocardial infarction. From the results, it can be seen that the hydrogel group can reduce ventricular dilation after mechanical treatment of the ventricular wall, and the ventricular contraction function is improved compared with the MI group.
  • the myocardial infarction area was also analyzed by histology. The blank group showed that the ventricular wall infarcted area was significantly thinned and the local structure was disordered.
  • hydrogel systems composed of different materials can also be applied to heart patches.
  • Example 40 Application of photo-crosslinked hydrogel to tissue engineering scaffold material-cartilage repair
  • articular cartilage Using New Zealand male white rabbits, they were divided into three groups for the repair experiment of articular cartilage: a: Hydrogel coated with chondrocytes (4% component A-15/3% component B-1/0.2% component C- 1) Group, namely Gel + chondrocyte group; b: Pure hydrogel (4% component A-15/3% component B-1/0.2% component C-1) group, namely Gel group; c: The untreated control group is the Control group.
  • the hydrogel precursor solution can fully penetrate and fill the defect of rabbit articular cartilage, and it adheres firmly to the defect after being glued under light without additional fixation. 12 weeks after the operation, the rabbits in the experiment were killed by intravenous air injection, and the damaged joints were extracted to evaluate the effect of the experiment.
  • hydrogel systems composed of different materials can also be applied to tissue engineering scaffold materials-cartilage repair.
  • SD rats were used for skull repair experiments, and the above SD rats were randomly divided into 3 groups: a: Hydrogel (30% component A-25/5% component B-1/1% component C-1 )+hydroxyapatite experimental group; b: hydrogel treatment (30% component A-25/5% component B-1/1% component C-1) group; c: control without material treatment Group.
  • they were intraperitoneally anesthetized with 4% chloral hydrate solution (0.9 mL per gram of body weight) and disinfected with iodine. Then, use a surgical blade to open the scalp of the rat's skull.
  • a dental trephine was used to symmetrically create a complete skull defect model with a diameter of 5mm on the left and right of the rat's skull.
  • the skull defect of SD rats was basically not repaired, and the edge of the skull defect filled with hydrogel had new osteogenesis, but the amount of new bone tissue was higher.
  • most of the defects have not been well repaired, and the skull defects filled with hydrogel + hydroxyapatite have basically been repaired, and a large amount of new bone tissue is formed in the defect.
  • the histological staining analysis was performed on the tissue sections of the skull using Van Gieson staining method.
  • hydrogel systems composed of different materials can also be applied to tissue engineering scaffold materials-bone repair.
  • 3D printing technology is a three-dimensional molding technology that has developed rapidly in recent years and has been widely used.
  • the current 3D printing technology includes fused deposition (FDM), light curing molding (SLA), laser sintering (SLS), continuous liquid surface Manufacturing type (CLIP) and so on.
  • FDM fused deposition
  • SLA light curing molding
  • SLS laser sintering
  • CLIP continuous liquid surface Manufacturing type
  • the method suitable for printing with cells is currently mainly FDM
  • the materials for printing with cells are mainly hydrogel materials. Therefore, the development of 3D printing bio-ink-printable hydrogel materials and the improvement of printing of hydrogel materials The resolution is the basic problem of research in this field.
  • hydrogel 3% component A-22/2% component B-1/0.2% component C-1
  • a certain mass concentration of the hydrogel precursor solution is uniformly mixed with the cells, and then loaded In the low-temperature printing barrel, control the printing temperature at about 25°C, adjust the viscosity of the bio-ink through the temperature to obtain the best printing state, and then determine the appropriate printing pressure and printing speed to perform bio-printing and printing with different structures
  • the hydrogel is cross-linked by light (or light while printing) to obtain a hydrogel with cells and structure for 3D cell culture.
  • DLP digital light processing 3D printing technology
  • SLA stereoscopic light curing
  • DLP has the advantages of fast printing speed and high resolution.
  • Most printing methods have incomparable advantages, and currently have certain application prospects in dental models, jewelry design and other fields.
  • the printing inks currently used in the market are limited to light-curable resins, and hydrogel as an emerging biological ink has not received widespread attention, mainly because there is no hydrogel material suitable for DLP printing, and the present invention proposes
  • the composite photo-crosslinked hydrogel material is very suitable for 3D printing due to its fast light curing speed and excellent mechanical properties, and it has higher printing accuracy.
  • hydrogel component (3% A-11/2% component B-1/0.2% component C-1) as an example, put a certain mass concentration of the hydrogel precursor solution into the liquid tank, and pass Controlling the intensity of the light source, exposure time and other parameters to adjust the printing conditions of the bio-ink, to obtain the best printing state, so as to obtain a structured 3D printing hydrogel (Figure 16).
  • hydrogel systems composed of different materials can also be applied to 3D printing (DLP) bio-inks.
  • DLP 3D printing
  • Hydrogel is a kind of cross-linked polymer network that can swell in water but not dissolve. Since most of the hydrogel is composed of water, it has very good biocompatibility and is especially suitable for drugs and bioactive macromolecules. Carrier. Drugs or bioactive macromolecules encapsulated in hydrogel materials achieve sustained drug release through molecular diffusion and material degradation.
  • the specific introduction is as follows: Take the hydrogel (30% component A-25/5% component B-1/1% component C-1) as an example, and dissolve it in physiological saline , Prepare a certain concentration of hydrogel precursor solution, add a certain amount of drug molecules, take 200 ⁇ L of the above solution and place it in a circular mold to form a hydrogel, then put it into a 24-well cell culture plate, and add a certain amount To evaluate the release effect of the material on drug release by analyzing the release amount of the drug in the solution by ultraviolet test.
  • hydrogel systems composed of different materials can also be applied to the packaging and release of drugs.

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Abstract

本发明涉及高强度和韧性的光交联水凝胶材料及其制备方法与应用。高强度和韧性的光交联水凝胶材料由邻硝基苄基类光扳机修饰的光敏高分子衍生物、双键官能团修饰的高分子衍生物、光引发剂为原料制备而成。本发明通过控制邻硝基苄基类光扳机修饰的光敏高分子衍生物中聚乙二醇及其衍生物的平均臂长，以及邻硝基苄基类光扳机与聚乙二醇及其衍生物的摩尔比，从而实现对水凝胶性质的显著提升，本发明相比于现有技术制备的水凝胶强度和/或韧性提高了一个数量级甚至更高，解决了当前水凝胶机械性能差的瓶颈问题，拓宽了水凝胶的应用范围。

Description

高强度和韧性的光交联水凝胶材料及其制备方法与应用 技术领域
本发明属于生物材料领域，尤其是涉及一种高强度和韧性的光交联水凝胶材料及其制备方法与应用。
背景技术
水凝胶是一类高度含水的具有三维网络交联结构的聚合物材料，由于其具有优异的生物相容性及一定的机械强度，可以高度拟合生物组织的微环境，因此广泛应用于组织工程和再生医学。在临床应用中，原位固化的水凝胶具有优异的组织赋型能力，光敏型水凝胶由于具有时空精确可控以及原位光固化的优势而更具备临床的实际操作性。然而当前光交联制备的水凝胶机械性能较差，传统光交联水凝胶的强度只有几十千帕，近年来发展的双网络水凝胶虽然一定程度上提高了光交联水凝胶的机械性能，但是能够适用于动态环境下的共价双网络水凝胶的强度最高也只有2MPa，远远没有达到人体一些软组织的强度需求，并且这些水凝胶还存在强度韧性不可兼得的矛盾，这些问题大大限制了光交联水凝胶的进一步应用。
在中国专利CN201711132472.2中公开了一种光交联凝胶技术，其中包含邻硝基苄基类光扳机修饰的聚乙二醇及其衍生物、双键官能团修饰的高分子衍生物以及光引发剂通过光交联凝胶化制备水凝胶的技术。中国专利CN201711132472.2的方案中，主要通过组分B-光引发剂的引入来提高原有邻硝基苄基类光扳机的交联速度及交联效率(通过产生极强反应活性的亚硝基自由基进行交联)，而且可以将光引发自由基聚合交联的高分子衍生物和光偶合反应交联的高分子衍生物混合后形成复合的光敏高分子溶液，在一次光照下，可以激活引发剂产生自由基，分别进行自由基交联，也可以发生光偶合反应交联及光致亚硝基交联，实现多重光交联制备复合型水凝胶。该技术制备的水凝胶材料光固化速度快，组织粘附力强，生物相容性好，并且具有较好的延展性和强度。
然而，通过本申请发明人在创造本申请过程中的研究发现，在中国专利CN201711132472.2提交时其并未发现聚乙二醇及其衍生物的平均臂长会对水凝胶机械性能产生影响，所以，中国专利CN201711132472.2公开的技术方案中并不涉及这方面的内容，因此中国专利CN201711132472.2制备的水凝胶的强度仅为1-2MPa左右，机械性能十分有限。
发明内容
针对当前光交联制备水凝胶机械性能差的不足，本发明提出一种高强度和韧性的光交联水凝胶材料及其制备方法与应用。
本发明通过光交联制备高强度、高韧性水凝胶。通过光敏分子基团修饰的高分子衍生物之间的交联反应将高分子骨架通过化学键连接在一起，从而有利于力在高分子骨架间的传递，提高水凝胶的机械性能，拓宽水凝胶的应用范围。
本发明的目的可以通过以下技术方案来实现：
本发明第一个目的，提供邻硝基苄基类光扳机修饰的光敏高分子衍生物。
所述邻硝基苄基类光扳机修饰的光敏高分子衍生物(即组分A)，具有式I结构：
Figure PCTCN2020106113-appb-000001
其中，R’选自氢、卤原子、羟基、巯基、胺基、硝基、氰基、醛基、酮基、酯基、酰胺基、膦酸基、膦酸酯基、磺酸基、磺酸酯基、砜基、亚砜基、芳基、杂芳基、烷基、亚烷基、改性烷基或改性亚烷基等，
R”选自C、N、O或S；
R 1选自氢、醚键类取代基、酯键类取代基、碳酸酯键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基等，
R 2，R 3，R 4，R 5独立地选自氢、卤原子、羟基、巯基、胺基、硝基、氰基、醛基、酮基、酯基、酰胺基、膦酸基、膦酸酯基、磺酸基、磺酸酯基、砜基、亚砜基、芳基、杂芳基、烷基、亚烷基、改性烷基或改性亚烷基等；
式I中，P 1与R 2，R 3，R 4，R 5中任意的一个或多个基团相连接，P 1不与R 1连接。
当式I结构中R 2，R 3，R 4，R 5中至少两个相互连接，与碳原子一起形成饱和或不饱和的脂环或脂杂环，或形成芳环或芳杂环时，P 1还可以连接于R 2，R 3，R 4，R 5之间形成的饱和或不饱和脂环或脂杂环，或形成的芳环或芳杂环。
对于P 1与R 2，R 3，R 4，R 5中任意的一个或多个基团相连接，或连接于R 2，R 3，R 4，R 5之间形成的饱和或不饱和脂环或脂杂环，或形成的芳环或芳杂环上时，连接键选自P 1-O-,P 1-S-,P 1-NH-,P 1-CH-,P 1-COO-,P 1-CONH-，该连接键的一端与P 1相连，另一端连接在式I所示分子的苯环上。
式I中，P 1为一种亲水或水溶性的多臂聚乙二醇或其衍生物，P 1具有以下通式：
Figure PCTCN2020106113-appb-000002
式II中PEG为单链聚乙二醇，
X，Y独立地选自聚乙二醇、聚丙二醇、聚乳酸、聚酯、聚羟基乙酸、聚乙烯醇、聚氨基酸、聚丙烯酸、聚甲基丙烯酸、聚丙烯酰胺、聚甲基丙烯酰胺、聚乙烯吡咯烷酮以及各种亲水性单体与亲水性单体、亲水性单体与疏水性单体、疏水性单体与疏水性单体的共聚物；
式II中，m≥1，R 6为多臂支化中心，支化度为2-8，式II中连接R 6结构部分分子量不小于6000，R 6选自以下结构中一种或两种以上的组合：
其中两臂支化中心包括以下结构：
Figure PCTCN2020106113-appb-000003
其中三臂支化中心包括以下结构：
Figure PCTCN2020106113-appb-000004
其中四臂支化中心包括以下结构：
Figure PCTCN2020106113-appb-000005
其中五臂支化中心包括以下结构：
Figure PCTCN2020106113-appb-000006
其中六臂支化中心包括以下结构：
Figure PCTCN2020106113-appb-000007
其中八臂支化中心包括以下结构：
Figure PCTCN2020106113-appb-000008
相同臂数的其它支化中心可以采用商业产品或者能够被简单聚合得到的结构。
进一步优选地，P 1为两臂聚乙二醇、三臂聚乙二醇、四臂聚乙二醇、六臂聚乙二醇或八臂聚乙二醇。
进一步优选地，P 1为20000分子量以上的两臂聚乙二醇或40000分子量以上的四臂聚乙二醇。
式I中，n≥2，即单条P 1高分子链上的邻硝基苄基类光扳机(即式Ⅰ中括号内的结构)的平均个数大于或等于2。
优选地，式I结构中，R 2，R 3，R 4，R 5中至少两个相互连接，与碳原子一起形成饱和或不饱和的脂环或脂杂环，或形成芳环或芳杂环。
进一步地，所述烷基为具有1～30个碳原子的饱和或不饱和脂肪族直链或支链的烷基；
所述亚烷基为具有1～30个碳原子的饱和或不饱和脂肪族直链或支链的亚烷基；
所述改性烷基为烷基的任意碳原子被选自卤原子、-OH、-SH、-NO 2、-CN、-CHO、 -COOH、酯基、酰胺基、芳基、亚芳基、-CO-、-O-、-S-、-SO-、-SO 2-、伯胺基、仲胺基、叔胺基、季铵盐基、饱和或不饱和的单环或双环亚环烃基、桥联脂杂环中的至少一种基团置换所得的基团，所述改性烷基具有1～30个原子，其碳碳单键可任意地被碳碳双键或碳碳叁键替换；
所述改性亚烷基为亚烷基的任意碳原子被选自卤原子、-OH、-SH、-NO 2、-CN、-CHO、-COOH、酯基、酰胺基、芳基、亚芳基、-CO-、-O-、-S-、-SO-、-SO 2-、伯胺基、仲胺基、叔胺基、季铵盐基、饱和或不饱和的单环或双环亚环烃基、桥联脂杂环中的至少一种基团置换所得的基团，所述改性亚烷基具有1～30个原子，其碳碳单键可任意地被碳碳双键或碳碳叁键替换；
所述醚键类取代基选自以下结构：
-O(CH 2) xCH 3、-(CH 2CH 2O) xCH 3、-(CH 2) x(CH 2CH 2O) yCH 3、或
Figure PCTCN2020106113-appb-000009
等，其中x和y≥0且为整数；
所述酯键类取代基选自以下结构：
-OCO(CH 2) xCH 3、O-CO(CH 2CH 2O) xCH 3、-OCO(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
所述碳酸酯键类取代基选自以下结构：
-OCOO(CH 2) xCH 3、-OCOO(CH 2CH 2O) xCH 3、-OCOO(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
所述胺基甲酸酯键类取代基选自以下结构：
-OCONH(CH 2) xCH 3、-OCONH(CH 2CH 2O) xCH 3、-OCONH(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
所述巯基甲酸酯键类取代基选自以下结构：
-OCOS(CH 2) xCH 3、-OCOS(CH 2CH 2O) xCH 3、-OCOS(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
所述磷酸酯键类取代基选自以下结构：
-POOO(CH 2) xCH 3、-POOO(CH 2CH 2O) xCH 3、-POOO(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
所述芳基为5～10元芳香单环或芳香稠合双环结构；
所述杂芳基为环上含有选自O、S、N或Si中的至少一种杂原子的5～10元芳香单环或芳香稠合双环结构；
所述卤原子各自独立地选自F、Cl、Br、I。
所述脂环为饱和或不饱和的3～10元单环或多环脂环；
所述脂杂环为环上含有选自O、S、N或Si中的至少一种杂原子的饱和或不饱和的3-10元单环或多环脂杂环，所述脂杂环上含有S原子时，其任选为-S-、-SO-或-SO 2-；所述脂环或脂杂环上的H还可任意地被卤原子、硝基、芳基、烷基或改性烷基取代；
所述芳环为5～10元芳香单环或芳香稠合双环；
所述芳杂环为环上含有选自O、S、N或Si中的至少一种杂原子的5～10元芳香单环或芳香稠合双环；所述芳环或芳杂环上的H还可任意地被卤原子、硝基、芳基、烷基或改性烷基取代。
进一步地，烷基类取代基优选结构，如直链烷基-(CH 2) xCH 3、支链烷基-(CH 2) x(CY’Y”) yCH 3(Y’，Y”为氢、烷基或改性烷基)等，其中x和y≥0且为整数；
进一步地，醚类取代基优选结构，如-O(CH 2) xCH 3、-O(CH 2CH 2O) xCH 3、-O(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
进一步地，硫醚类取代基优选结构，如-S(CH 2) xCH 3、-S(CH 2CH 2O) xCH 3、-S(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
进一步地，胺基类取代基优选结构，如-NH(CH 2) xCH 3、-NH(CH 2) x(CY’Y”) yCH 3、-N(CY’Y”) x(CY’Y”) y、
Figure PCTCN2020106113-appb-000010
(Y’，Y”为氢、烷基或改性烷基)等，其中x和y≥0且为整数；
进一步地，酯类取代基优选结构，如-COO(CH 2) xCH 3、-COO(CH 2CH 2O) xCH 3、-COO(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
进一步地，酰胺类取代基优选结构，如-CONH(CH 2) xCH 3、-CONH(CH 2CH 2O) xCH 3、-CONH(CH 2) x(CH 2CH 2O) yCH 3等，其中x和y≥0且为整数；
进一步地，芳香族类取代基优选结构，如-Ph、
Figure PCTCN2020106113-appb-000011
等。
进一步地，脂环或脂杂环的优选结构包括：
Figure PCTCN2020106113-appb-000012
等；
进一步地，芳环或芳杂环的优选结构包括：
Figure PCTCN2020106113-appb-000013
等。
R’的一些优选结构包括：
-H、-CH 3、-CH 2CH 3、-CH＝CH-CH＝CH-CH 3、-F、-Cl、-Br、-I、-CF 3、-CCl 3、-CBr 3、-CI 3、-CN、-COOH、-Ph、
Figure PCTCN2020106113-appb-000014
等。
R 2，R 3，R 4，R 5的一些优选结构包括：-H、-OH、-SH、-NH 2、-F、-Cl、-Br、-I、-CF 3、-CCl 3、-CBr 3、-CI 3、-NO 2、-CN、-CHO、-COOH、-COONH 2、-SO 3H等。
进一步优选，所述式I可选自以下组分A-1～组分A-30中的结构：
Figure PCTCN2020106113-appb-000015
Figure PCTCN2020106113-appb-000016
Figure PCTCN2020106113-appb-000017
Figure PCTCN2020106113-appb-000018
本发明的第二个目的，提供高强度和韧性的光交联水凝胶材料。
所述高强度和韧性的光交联水凝胶材料由三种组分为原料制备而成，三种原料分别为：
邻硝基苄基类光扳机修饰的光敏高分子衍生物，简称组分A；
双键官能团修饰的高分子衍生物，简称组分B；
光引发剂，简称组分C。
本发明的光交联水凝胶材料，也可以称为复合型光交联水凝胶材料。
其中，组分A即本发明第一方面提供的邻硝基苄基类光扳机修饰的光敏高分子衍生物。
所述双键官能团修饰的高分子衍生物，简称组分B，具有式III所示结构：
Figure PCTCN2020106113-appb-000019
式III中，R 1’，R 2’、R 3’独立地选自氢、卤原子、芳环、杂芳环、脂环、脂杂环、烷基或改性烷基；R 4’选自烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基；
n≥2，即单条P 1’高分子链上的双键官能团的平均个数大于或等于2。
式III中卤原子、芳环、杂芳环、脂环、脂杂环、烷基、改性烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基的定义与式I中卤原子、芳环、杂芳环、脂环、脂杂环、烷基、改性烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基的定义相同，只是式III中卤原子、芳环、杂芳环、脂环、脂杂环、烷基、改性烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基的选择可以不同于式I。
P 1’为一种亲水或水溶性天然高聚物或合成高聚物，或P 1’独立的选自多种亲水或水溶性天然高聚物或合成高聚物等；
所述亲水或水溶性天然高聚物包括天然多糖类物质及其修饰物或降解物，蛋白及其修饰物、改性物和降解的多肽类物质等；
所述天然多糖类物质包括透明质酸、羧甲基纤维素、甲基纤维素、羟乙基纤维素、羟丙基纤维素、海藻酸、葡聚糖、琼脂糖、肝素、硫酸软骨素、乙二醇壳聚糖、丙二醇壳聚糖、壳聚糖乳酸盐、羧甲基壳聚糖或壳聚糖季铵盐；
所述蛋白包括各种亲水性或水溶性动植物蛋白、胶原蛋白、血清蛋白、丝素蛋白、弹性蛋白，所述蛋白降解物包括明胶或多肽；
亲水或水溶性合成高聚物包括两臂或多臂聚乙二醇、聚乙烯亚胺、树枝体、合成多肽、聚氨基酸、聚丙烯酸、聚甲基丙烯酸、聚丙烯酰胺、聚甲基丙烯酰胺、聚乙烯醇、聚乙烯吡咯烷酮以及各种亲水性单体与亲水性单体、亲水性单体与疏水性单体的亲水或水溶性共聚物。
可选地，P 1’选自透明质酸、羧甲基纤维素、甲基纤维素、羟乙基纤维素、羟丙基纤维素、海藻酸、葡聚糖、琼脂糖、肝素、硫酸软骨素、乙二醇壳聚糖、丙二醇壳聚糖、壳聚糖乳酸盐、羧甲基壳聚糖、壳聚糖季铵盐。
进一步优选地，所述式III双键官能团修饰的高分子衍生物，可选自以下组分B-1～组分B-8中的结构：
Figure PCTCN2020106113-appb-000020
Figure PCTCN2020106113-appb-000021
组分B-1～组分B-8中，m,n≥2。
所述光引发剂，简称组分C，为光照下能够产生自由基的物质。
可选地，组分C为水溶性光引发剂或可分散在水中的光引发剂；
可选地，组分C为LAP(组分C-1)，I 2959(组分C-2)，Eosin-Y(组分C-3)，二苯甲酮(组分C-4)，Na-TPO(组分C-5)等及其衍生物；
可选地，组分C为LAP，Na-TPO及其衍生物；
Figure PCTCN2020106113-appb-000022
本发明的目的之三，在于提供所述高强度和韧性的光交联水凝胶材料的制备方法。
所述高强度和韧性的光交联水凝胶材料的制备方法，包括以下步骤：
组分A，组分B和组分C溶于生物相容性介质得到水凝胶前体溶液；
水凝胶前体溶液在光源照射下，发生光交联形成水凝胶。
其中，获得水凝胶前体溶液的方式可以采用以下两种方式：
方式一：将组分A溶于生物相容性介质得到溶液A；将组分B溶于生物相容性介质得到溶液B；将组分C溶于生物相容性介质得到溶液C；将溶液A，溶液B和溶液C混合均匀得到水凝胶前体溶液。
方式二：将组分A，组分B和组分C混合溶于生物相容性介质得到水凝胶前体溶液。
在本发明的一些实施方式中，所述生物相容性介质选自蒸馏水、生理盐水、缓冲液、脱细胞基质或细胞培养基溶液。根据不同的应用，可选取不同的介质。
在本发明的一些实施方式中，混合均匀形成的水凝胶前体溶液中，组分A浓度为0.1％wt-60％wt，优选为1％wt-40％wt，组分B的浓度为0.01％wt-20％wt，优选为0.05％wt-10％wt，组分C的浓度为0.01％wt-5％wt，优选为0.1％wt-3％wt，高分子总浓度为0.1％wt-60％wt，优选为1％wt-10％wt。
在本发明的一些实施方式中，光源的波长根据邻硝基苄类光扳机及光引发剂的吸收波长来确定，可以为250-500nm，优选为300-450nm，进一步优选为365、375、385、395、405nm。
水凝胶前体溶液在光源照射下，发生光交联的技术原理为：组分A中的邻硝基苄基类光扳机与组分C-光引发剂在光照下，发生自由基反应，同时组分B中的双键官能团与组分C-光引发剂在光照下发生自由基聚合，两种反应产生的自由基进一步反应交联形成水凝胶。
本发明提供的光交联水凝胶材料的特征主要在于：组分A(邻硝基苄基类光扳机修饰的光敏高分子衍生物)与组分B(双键官能团修饰的高分子衍生物)通过组分C(光引发剂)聚合形成水凝胶，当组分A中聚乙二醇及其衍生物的平均臂长达到一定分子量时，水凝胶的强度和韧性显著提高(具体数据如实施例19～22)。基于此发现，本发明将这类水凝胶的强度和/或韧性提高了一个数量级甚至更高，解决了当前水凝胶机械性能差的瓶颈问题，拓宽了水凝胶的应用范围。
本发明的目的之四，在于提供一种用于制备本发明所述高强度和韧性的光交联水凝胶材料的试剂盒。
所述试剂盒包含：组分A-邻硝基苄基类光扳机修饰的光敏高分子衍生物；组分B-双键官能团修饰的高分子衍生物，组分C-光引发剂及有关水凝胶制备及应用的说明书。
对于以上试剂盒中还可包含生物相容性介质，如蒸馏水、生理盐水、缓冲液和细胞培养基。
对于以上试剂盒中的说明书上记载着水凝胶的应用包括其在术后创面封闭、组织液渗漏封堵、止血材料、组织工程支架材料、3D打印的生物墨水及作为细胞、蛋白或药物载体上的应用。
本发明的目的之五，在于提供所述高强度和韧性的光交联水凝胶材料的应用。
本发明提供了所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-组织免缝合材料或药物的应用。
本发明提供了所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-组织修复材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-术后防黏连材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-口腔溃疡材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备组织液渗漏封堵-肠漏封堵材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备组织液渗漏封堵-脑脊液封堵材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备组织液渗漏封堵-胃漏封堵材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备止血材料-肝脏止血材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备止血材料-肾脏止血材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备止血材料-脾脏止血材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备止血材料-胰止血材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备止血材料-骨断面止血材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备止血材料-动脉止血材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备止血材料-心脏止血材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-补片固定材料的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-瓣膜固定材料的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-黏膜固定材料的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-组织固定材料的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-骨固定材料的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备组织加固材料-贴片材料的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备组织工程支架材料-软骨修复材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备组织工程支架材料-骨修复材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备组织工程支架材料-骨/软骨复合缺损修复材料或药物的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料在3D打印(FDM)材料-生 物墨水的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料在3D打印(SLA)材料-生物墨水的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料在3D打印(DLP)材料-生物墨水的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料在3D打印-结合介入科手术的应用。
本发明还提供了所述高强度和韧性的光交联水凝胶材料作为制备细胞、蛋白、药物载体上的应用。
本发明通过控制组分A中聚乙二醇及其衍生物的平均臂长，以及邻硝基苄基类光扳机与聚乙二醇及其衍生物的摩尔比，从而实现对水凝胶性质的显著提升，本发明相比于现有技术(如CN201711132472.2)制备的水凝胶强度和/或韧性提高了一个数量级甚至更高(具体数据如实施例19～22)，解决了当前水凝胶机械性能差的瓶颈问题，拓宽了水凝胶的应用范围。
同时，本发明保留了水凝胶制备技术固化速度快，组织粘附力强，生物相容性好等技术优势，因此，与现有技术相比，本发明具有如下优点及有益效果：
(1)机械性能优异，具有非常高的强度(最高15MPa)和韧性(最高12MJ m -3)，改变了水凝胶的力学属性，其强度/韧性超过当前绝大多数水凝胶；
(2)组织粘附力强，能在组织表面原位凝胶化，同时光照产生的醛基/酮基和亚硝基能与组织表面的巯基、胺基、羧基发生反应，实现水凝胶与周围组织的化学键键连一体化整合，克服了自由基聚合交联需要额外底涂的问题；
(3)生物相容性好，原料主要来源于天然高分子材料，且形成的水凝胶可降解；
(4)光固化速度快，能在10s内达到成胶点，20s达到最终模量；
(5)临床操作便捷，由于光交联具有优异的时空可控性，使用时可将水凝胶前体溶液涂抹或喷涂于组织表面，在光照下快速与组织粘附整合，无需底涂，一步实现组织表面原位成胶。
附图说明
图1为水凝胶前体溶液(30％组分A-25/5％组分B-1/1％组分C-1)，(4％组分A-15/3％组分B-1/0.2％组分C-1)，(30％4APEG50/5％组分B-1/2％组分C-1)以及(4％4APEG50/3％组分B-1/0.2％组分C-1)光照成胶的实时流变图。
图2为水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)，(4％组分A-15/3％组分B-1/0.2％组分C-1)，(30％4APEG50/5％组分B-1/2％组分C-1)以及(4％4APEG50/3％组分B-1/0.2％组分C-1)的压缩应力应变曲线。
图3为水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)，(4％组分A-15/3％组分B-1/0.2％组分C-1)，(30％4APEG50/5％组分B-1/2％组分C-1)以及(4％4APEG50/3％组分B-1/0.2％组分C-1)的拉伸应力应变曲线。
图4为水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)的创面封闭-组织免缝合效果直观图。
图5为水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)的创面封闭-皮肤修复的效果直观图。
图6为水凝胶(3％组分A-22/2％组分B-1/0.2％组分C-1)创面封闭-宫颈切除术后促修复的效果直观图。
图7为水凝胶(3％组分A-12/2％组分B-1/0.2％组分C-1)创面封闭-痔疮切除术后促修复的效果直观图。
图8为水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)创面封闭-腹腔术后防黏连的效果直观图。
图9为水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)创面封闭-声带术后防黏连的效果直观图。
图10为水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)创面封闭-口腔溃疡的效果直观图。
图11为水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)作为止血材料-肝脏止血的效果直观图。
图12为水凝胶(3％组分A-22/2％组分B-1/0.2％组分C-5)作为止血材料-肾脏止血的效果直观图。
图13为该水凝胶(3％组分A-12/2％组分B-1/0.2％组分C-1)作为止血材料-心脏止血的效果直观图。
图14为水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)作为疝气补片固定材料的效果直观图。
图15为水凝胶(30％组分A-26/5％组分B-1/1％组分C-1)作为心脏贴片的效果直观图。
图16为水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)作为生物墨水的3D打印(DLP)效果直观图。
具体实施方式
下面结合附图和具体实施例对本发明进行详细说明。
实施例一：组分A-2的合成
Figure PCTCN2020106113-appb-000023
(1)化合物1的合成：参考文献Yunlong Yang；Jieyuan Zhang；Zhenzhen Liu；Qiuning Lin；Xiaolin Liu；Chunyan Bao；Yang Wang；Linyong Zhu.Adv.Mater.2016,28,2724.公开的方法进行合成。 1H NMR(400MHz,CDCl 3):δ＝7.71(s,1H),7.35(d,1H),7.22(d,1H),4.96(s,2H),4.13(t,J＝6.1Hz,2H),3.32(dd,J＝11.6,5.7Hz,2H),2.82(t,J＝5.9Hz,2H),2.44(t,J＝7.2Hz,2H),2.26-2.17(m,2H).
(2)组分A-2的合成：将聚乙二醇(8g)溶解在无水CH 2Cl 2(100mL)中，加入4-二甲基氨基吡啶(DAMP；0.005g)和三乙胺(0.101g)，将上述混合溶液滴加到4-硝基氯甲酸苯酯(0.201g)的无水CH 2Cl 2(3mL)溶液中。将溶液在室温下搅拌5小时。减压除去溶剂至溶剂约为原始体积的一半，将反应体系倒入Et 2O中，过滤收集得到的白色固体，重复上述重沉过程至完全除去4-硝基氯甲酸苯酯等未反应的原料，得到化合物1(7.8g)。将干燥后的化合物溶于无水DMF(50mL)中，再加入0.1mL TEA和化合物1(0.327g)。得到的混合物在室温下再搅拌6小时。减压除去溶剂，将混合物用CH 2Cl 2重新溶解并依次用NaOH水溶液(1.0M)和HCl水溶液(1.0M)洗涤三次，分别除去对硝基苯酚和NB，TEA等杂质。有机相用无水Na 2SO 4干燥，减压除去溶剂至溶剂约为原始体积的一半，将其倒入Et 2O中。过滤收集得到的浅黄色固体，得到组分A-2(7.2g)，产率90％。通过 1H NMR光谱测定，7.3-7.9ppm处的峰属于端基中的质子，并且可通过该位移计算标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,1818H),7.33(s,2H),7.43(s,2H),7.81(s,2H),4.96(s,4H)，2.43(q,4H),2.12(m,4H)。
实施例二：组分A-3的合成
Figure PCTCN2020106113-appb-000024
(1)化合物2的合成：参考文献Yunlong Yang；Jieyuan Zhang；Zhenzhen Liu；Qiuning Lin；Xiaolin Liu；Chunyan Bao；Yang Wang；Linyong Zhu.Adv.Mater.2016,28,2724.公开的方法进行合成。 1H NMR(400MHz,CDCl 3):δ＝7.71(s,1H),7.22(s,1H),4.96(q,2H),4.13(t,J＝6.1Hz,2H),3.99(s,3H),3.32(dd,J＝11.6,5.7Hz,2H),2.82(t,J＝5.9Hz,2H),2.44(t,J＝7.2Hz,2H),2.26-2.17(m,2H),1.56(t,3H).
(2)组分A-3的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,1818H),7.33(s,2H),7.81(s,2H),4.96(q,4H),2.43(q,4H),2.12(m,4H)。
实施例三：组分A-9的合成
Figure PCTCN2020106113-appb-000025
组分A-9的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,3636H),7.33(s,3H),7.81(s,3H),4.96(q,6H),2.43(q,6H),2.12(m,6H)。
实施例四：组分A-12的合成
Figure PCTCN2020106113-appb-000026
组分A-12的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,3636H),7.33(s,4H),7.81(s,4H),4.96(q,8H),2.43(q,8H),2.12(m,8H)。
实施例五：组分A-16的合成
Figure PCTCN2020106113-appb-000027
(1)化合物3的合成：参考文献Emmanuel Riguet and Christian G.Bochet,Org.Lett.2007,9,26,5453-545.公开的方法进行合成。 1H NMR(400MHz,CDCl 3):δ2.90(bs,1H),3.05(s,3H),3.40(m,4H),3.85(m,4H),4.94(s,2H),6.75(dd,1H),7.03(d,1H),8.14(d,1H)。
(2)组分A-16的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,3636H),4.94(s,8H),6.75(dd,4H),7.03(d,4H),8.14(d,4H)。
实施例六：组分A-18的合成
Figure PCTCN2020106113-appb-000028
(1)化合物4的合成：参考文献Emmanuel Riguet and Christian G.Bochet,Org.Lett.2007,9,26,5453-545.公开的方法进行合成。 1H NMR(400MHz,CDCl 3):δ7.71(s,1H),7.22(s,1H),4.24(s,2H),3.32(t,2H),2.82(t,2H),2.75(t,2H),2.00-1.91(m,2H).
(2)组分A-18的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,3636H),4.24(s,8H),7.71(s,4H),7.22(s,4H)。
实施例七：组分A-20的合成
Figure PCTCN2020106113-appb-000029
(1)化合物5的合成：参考文献Emmanuel Riguet and Christian G.Bochet,Org.Lett.2007,9,26,5453-545.公开的方法进行合成。 1H NMR(400MHz,CDCl 3):δ7.71(s,1H),7.22(s,1H),4.24(s,2H),3.32(m,2H),2.82(t,2H),2.75(t,2H),2.00-1.91(m,2H).
(2)组分A-20的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,3636H),4.24(s,8H),7.71(s,4H),7.22(s,4H)。
实施例八：组分A-21的合成
Figure PCTCN2020106113-appb-000030
组分A-21的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,3220H),7.33(s,4H),7.81(s,4H),4.96(s,8H),1.53(s,420H)。
实施例九：组分A-22的合成
Figure PCTCN2020106113-appb-000031
组分A-22的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,2940H),7.33(s,4H),7.81(s,4H),4.96(s,8H),1.53(s,420H)。
实施例十：组分A-23的合成
Figure PCTCN2020106113-appb-000032
组分A-23的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,2900H),7.33(s,4H),7.81(s,4H),4.96(s,8H),2.53(m,180H),1.53(m,500H)。
实施例十一：组分A-26的合成
Figure PCTCN2020106113-appb-000033
组分A-26的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,6400H),7.33(s,4H),7.81(s,4H),4.96(s,8H),1.53(s,850H)。
实施例十二：组分A-27的合成
Figure PCTCN2020106113-appb-000034
组分A-27的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,6000H),7.33(s,4H),7.81(s,4H),4.96(s,8H),1.53(s,850H)。
实施例十三：组分A-28的合成
Figure PCTCN2020106113-appb-000035
组分A-28的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,5800H),7.33(s,4H),7.81(s,4H),4.96(s,8H),2.53(m,360H),1.53(m,1000H)。
对比实施例十四：
Figure PCTCN2020106113-appb-000036
PEG50的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,454H),7.33(s,2H),7.81(s,2H),4.96(s,4H)。
对比实施例十五：
Figure PCTCN2020106113-appb-000037
PEG100的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,900H),7.33(s,2H),7.81(s,2H),4.96(s,4H)。
对比实施例十六：
Figure PCTCN2020106113-appb-000038
4APEG25的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,450H),7.33(s,4H),7.81(s,4H),4.96(s,8H)。
对比实施例十七：
Figure PCTCN2020106113-appb-000039
4APEG50的合成：参照组分A-2的合成方法。通过 1H NMR光谱测定标记率(3.4-3.6)。 1H NMR(400MHz,D 2O):δ3.72(s,900H),7.33(s,4H),7.81(s,4H),4.96(s,8H)。
实施例十八：光交联方法制备水凝胶
按照本发明方法，于37℃下操作，制得不同的水凝胶前体溶液，如表1所示。
表1
Figure PCTCN2020106113-appb-000040
Figure PCTCN2020106113-appb-000041
将上述不同凝胶溶液分别在365、395nm或405nm(20mW/cm 2)条件下光照一定时间，即可得到不同化学组成的水凝胶。不同的凝胶材料具有不同的生物效应，可以根据不同的应用针对性地选择凝胶材料的组成。
注：组分A…为组分A-2～A-30，(4A)PEG…为PEG50，PEG100，4APEG25，4APEG50；组分C…为组分C-1～C-5。
表1中1-40wt％为水凝胶前体溶液优选的质量浓度范围。
实施例十九：光交联方法制备水凝胶流变测试
流变分析采用HAAKE MARS流变仪，在37℃的测试平台
Figure PCTCN2020106113-appb-000042
上进行流变测试。本实例研究了紫外光照时间、光照强度和高分子衍生物的质量浓度对水凝胶成胶时间和储存模量的影响。图1实验组水凝胶前体溶液(30％组分A-25/5％组分B-1/1％组分C-1)和水凝胶前体溶液(4％组分A-15/3％组分B-1/0.2％组分C-1)，以及对照组水凝胶前体溶液(30％4APEG50/5％组分B-1/2％组分C-1)和水凝胶前体溶液(4％4APEG50/3％组分B-1/0.2％组分C-1)光照成胶的实时流变图(流变测试中，G’为储能模量，G”为损耗模量，当G’超过G”时即为凝胶点)。从图1中看出，实验组溶液在约3s时开始成胶，直至20s左右完全成胶，且完全成胶时的模量分别可以达到116,400Pa(图1a)、14,700Pa(图1b)，而对照组溶液完全成胶时的模量分别为10,500Pa(图1c)、4,500Pa(图1d)，实验组水凝胶储能模量分别是对照组的10倍和3倍，说明无论是高质量浓度还是低质量浓度，实验组水凝胶的储能模量均显著高于对照组。其它不同配比的水凝胶储能模量也均显著高于对照组，具体数据如表2所示。
表2
水凝胶材料组成 成胶点(s) 凝胶强度(Pa)
组分A-4/组分B-1/组分C-1(30％wt:5％wt:1％wt) 2～5 113,000
组分A-5/组分B-1/组分C-2(30％wt:5％wt:1％wt) 2～5 115,000
组分A-7/组分B-1/组分C-5(30％wt:5％wt:2％wt) 2～5 102,000
组分A-10/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 114,500
组分A-11/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 106,200
组分A-12/组分B-1/组分C-5(30％wt:5％wt:2％wt) 2～5 111,050
组分A-13/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 104,000
组分A-15/组分B-1/组分C-2(30％wt:5％wt:2％wt) 2～5 101,300
组分A-16/组分B-1/组分C-5(30％wt:5％wt:2％wt) 2～5 100,000
组分A-21/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 100,500
组分A-22/组分B-1/组分C-2(30％wt:5％wt:2％wt) 2～5 114,000
组分A-23/组分B-1/组分C-5(30％wt:5％wt:2％wt) 2～5 104,500
组分A-25/组分B-1/组分C-1(30％wt:5％wt:1％wt) 2～5 116,400
组分A-26/组分B-1/组分C-1(30％wt:5％wt:1％wt) 2～5 115,500
组分A-29/组分B-1/组分C-5(30％wt:5％wt:2％wt) 2～5 110,100
组分A-4/组分B-2/组分C-1(30％wt:5％wt:1％wt) 2～5 110,030
组分A-5/组分B-3/组分C-2(30％wt:5％wt:1％wt) 2～5 119,000
组分A-7/组分B-4/组分C-5(30％wt:5％wt:2％wt) 2～5 103,000
组分A-10/组分B-5/组分C-1(30％wt:5％wt:2％wt) 2～5 112,000
组分A-11/组分B-6/组分C-2(30％wt:5％wt:2％wt) 2～5 109,050
组分A-12/组分B-2/组分C-5(30％wt:5％wt:2％wt) 2～5 104,040
组分A-13/组分B-3/组分C-1(30％wt:5％wt:2％wt) 2～5 105,050
组分A-15/组分B-4/组分C-2(30％wt:5％wt:2％wt) 2～5 111,000
组分A-16/组分B-5/组分C-5(30％wt:5％wt:2％wt) 2～5 102,300
组分A-21/组分B-6/组分C-1(30％wt:5％wt:2％wt) 2～5 99,000
组分A-22/组分B-2/组分C-2(30％wt:5％wt:2％wt) 2～5 101,500
组分A-23/组分B-3/组分C-5(30％wt:5％wt:2％wt) 2～5 114,000
组分A-25/组分B-4/组分C-1(30％wt:5％wt:1％wt) 2～5 114,150
组分A-26/组分B-5/组分C-2(30％wt:5％wt:1％wt) 2～5 106,240
组分A-29/组分B-6/组分C-5(30％wt:5％wt:2％wt) 2～5 105,450
PEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 1,320
PEG100/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 2,430
4APEG25/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 2,510
4APEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 2～5 10,500
4APEG50/组分B-1/组分C-5(30％wt:5％wt:2％wt) 2～5 11,400
4APEG50/组分B-2/组分C-1(30％wt:5％wt:2％wt) 2～5 16,450
组分A-12/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 2～5 6,500
组分A-12/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 2～5 6,350
组分A-12/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2～5 14,000
组分A-12/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 2～5 14,500
组分A-15/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 2～5 6,100
组分A-15/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 2～5 6,250
组分A-15/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2～5 14,700
组分A-15/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 2～5 14,200
组分A-22/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 2～5 6,600
组分A-22/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 2～5 6,550
PEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2～5 2,100
PEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 2～5 1,050
PEG100/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2～5 1,520
PEG100/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 2～5 940
4APEG25/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2～5 1,500
4APEG25/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 2～5 1,300
4APEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2～5 4,500
4APEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 2～5 4,400
实施例二十：光交联水凝胶压缩性能测试
压缩性能测试采用GT-TCS-2000拉力机，压缩测试样品为直径10mm，高3mm的圆柱形试样，测试速度为1mm/min。图2为实验组水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)和水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)，以及对照组水凝胶(30％4APEG50/5％组分B-1/2％组分C-1)和水凝胶(4％4APEG50/3％组分B-1/0.2％组分C-1)的压缩性能。从图2中看出，实验组水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)和水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)压缩强度为分别为36.4MPa(图2a)和2.2MPa(图2b)；对照组水凝胶(30％4APEG50/5％组分B-1/2％组分C-1)和水凝胶(4％4APEG50/3％组分B-1/0.2％组分C-1)压缩强度为5.4MPa(图2c)和0.4MPa(图2d)。实验组水凝胶压缩强度分别是对照组的6.7倍和5.5倍，说明无论是高质量浓度还是低质量浓度，实验组水凝胶的压缩强度均显著高于对照组。其它不同配比的水凝胶压缩强度也均显著高于对照组，具体数据如表3所示。
表3
水凝胶材料组成 压缩强度(MPa)
组分A-4/组分B-1/组分C-1(30％wt:5％wt:1％wt) 30.9
组分A-5/组分B-1/组分C-2(30％wt:5％wt:1％wt) 32.4
组分A-7/组分B-1/组分C-5(30％wt:5％wt:2％wt) 35.3
组分A-10/组分B-1/组分C-1(30％wt:5％wt:2％wt) 35.9
组分A-11/组分B-1/组分C-1(30％wt:5％wt:2％wt) 36.2
组分A-12/组分B-1/组分C-5(30％wt:5％wt:2％wt) 31.4
组分A-13/组分B-1/组分C-1(30％wt:5％wt:2％wt) 35.9
组分A-15/组分B-1/组分C-2(30％wt:5％wt:2％wt) 34.7
组分A-16/组分B-1/组分C-5(30％wt:5％wt:2％wt) 32.5
组分A-21/组分B-1/组分C-1(30％wt:5％wt:2％wt) 33.8
组分A-22/组分B-1/组分C-2(30％wt:5％wt:2％wt) 34.5
组分A-23/组分B-1/组分C-5(30％wt:5％wt:2％wt) 32.8
组分A-25/组分B-1/组分C-1(30％wt:5％wt:1％wt) 36.4
组分A-26/组分B-1/组分C-1(30％wt:5％wt:1％wt) 36.6
组分A-29/组分B-1/组分C-5(30％wt:5％wt:2％wt) 35.7
组分A-4/组分B-2/组分C-1(30％wt:5％wt:1％wt) 34.8
组分A-5/组分B-3/组分C-2(30％wt:5％wt:1％wt) 33.8
组分A-7/组分B-4/组分C-5(30％wt:5％wt:2％wt) 31.5
组分A-10/组分B-5/组分C-1(30％wt:5％wt:2％wt) 34.9
组分A-11/组分B-6/组分C-2(30％wt:5％wt:2％wt) 34.2
组分A-12/组分B-2/组分C-5(30％wt:5％wt:2％wt) 32.8
组分A-13/组分B-3/组分C-1(30％wt:5％wt:2％wt) 33.5
组分A-15/组分B-4/组分C-2(30％wt:5％wt:2％wt) 33.2
组分A-16/组分B-5/组分C-5(30％wt:5％wt:2％wt) 32.7
组分A-21/组分B-6/组分C-1(30％wt:5％wt:2％wt) 35.1
组分A-22/组分B-2/组分C-2(30％wt:5％wt:2％wt) 33.9
组分A-23/组分B-3/组分C-5(30％wt:5％wt:2％wt) 34.5
组分A-25/组分B-4/组分C-1(30％wt:5％wt:1％wt) 33.3
组分A-26/组分B-5/组分C-2(30％wt:5％wt:1％wt) 32.4
组分A-29/组分B-6/组分C-5(30％wt:5％wt:2％wt) 32.9
PEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 1.1
PEG100/组分B-1/组分C-1(30％wt:5％wt:2％wt) 3.2
4APEG25/组分B-1/组分C-1(30％wt:5％wt:2％wt) 1.5
4APEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 5.4
4APEG50/组分B-1/组分C-5(30％wt:5％wt:2％wt) 5.8
4APEG50/组分B-2/组分C-1(30％wt:5％wt:2％wt) 4.4
组分A-12/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 1.1
组分A-12/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 1.2
组分A-12/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2.0
组分A-12/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 1.9
组分A-15/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 1.3
组分A-15/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 1.2
组分A-15/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 2.2
组分A-15/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 2.1
组分A-22/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 1.2
组分A-22/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 1.1
PEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.3
PEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.2
PEG100/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.3
PEG100/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.2
4APEG25/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.3
4APEG25/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.2
4APEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.4
4APEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.4
实施例二十一：光交联水凝胶拉伸性能测试
拉伸性能测试采用GT-TCS-2000拉力机，拉伸测试样品为长20mm，宽3mm，厚2mm的哑铃型试样，测试速度为5mm/min。图3为实验组水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)和水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)，以及对照组水凝胶(30％4APEG50/5％组分B-1/2％组分C-1)和水凝胶(4％4APEG50/3％组分B-1/0.2％组分C-1)的拉伸性能。从图3看出，实验组水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)和水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)拉伸强度分别为15.1MPa(图3a)和1.2MPa(图3b)；对照组水凝胶(30％4APEG50/5％组分B-1/2％组分C-1)和水凝胶(4％4APEG50/3％组分B-1/0.2％组分C-1)拉伸强度为1.8MPa(图3c)和0.4MPa(图3d)。实验组水凝胶拉伸强度分别是对照组的8倍和3倍，说明无论是高质量浓度还是低质量浓度，实验组水凝胶的拉伸强度均显著高于对照组。其它不同配比的水凝胶拉伸强度也均显著高于对照组，具体数据如表4所示。
表4
水凝胶材料组成 拉伸强度(MPa)
组分A-4/组分B-1/组分C-1(30％wt:5％wt:1％wt) 11.3
组分A-5/组分B-1/组分C-2(30％wt:5％wt:1％wt) 12.1
组分A-7/组分B-1/组分C-5(30％wt:5％wt:2％wt) 13.8
组分A-10/组分B-1/组分C-1(30％wt:5％wt:2％wt) 12.5
组分A-11/组分B-1/组分C-1(30％wt:5％wt:2％wt) 11.8
组分A-12/组分B-1/组分C-5(30％wt:5％wt:2％wt) 10.7
组分A-13/组分B-1/组分C-1(30％wt:5％wt:2％wt) 11.4
组分A-15/组分B-1/组分C-2(30％wt:5％wt:2％wt) 11.5
组分A-16/组分B-1/组分C-5(30％wt:5％wt:2％wt) 12.5
组分A-21/组分B-1/组分C-1(30％wt:5％wt:2％wt) 10.1
组分A-22/组分B-1/组分C-2(30％wt:5％wt:2％wt) 10.6
组分A-23/组分B-1/组分C-5(30％wt:5％wt:2％wt) 11.2
组分A-25/组分B-1/组分C-1(30％wt:5％wt:1％wt) 15.1
组分A-26/组分B-1/组分C-1(30％wt:5％wt:1％wt) 12.2
组分A-29/组分B-1/组分C-5(30％wt:5％wt:2％wt) 10.6
组分A-4/组分B-2/组分C-1(30％wt:5％wt:1％wt) 10.7
组分A-5/组分B-3/组分C-2(30％wt:5％wt:1％wt) 10.6
组分A-7/组分B-4/组分C-5(30％wt:5％wt:2％wt) 10.8
组分A-10/组分B-5/组分C-1(30％wt:5％wt:2％wt) 12.5
组分A-11/组分B-6/组分C-2(30％wt:5％wt:2％wt) 11.1
组分A-12/组分B-2/组分C-5(30％wt:5％wt:2％wt) 12.6
组分A-13/组分B-3/组分C-1(30％wt:5％wt:2％wt) 13.2
组分A-15/组分B-4/组分C-2(30％wt:5％wt:2％wt) 10.7
组分A-16/组分B-5/组分C-5(30％wt:5％wt:2％wt) 11.9
组分A-21/组分B-6/组分C-1(30％wt:5％wt:2％wt) 10.8
组分A-22/组分B-2/组分C-2(30％wt:5％wt:2％wt) 12.6
组分A-23/组分B-3/组分C-5(30％wt:5％wt:2％wt) 10.6
组分A-25/组分B-4/组分C-1(30％wt:5％wt:1％wt) 11.5
组分A-26/组分B-5/组分C-2(30％wt:5％wt:1％wt) 11.1
组分A-29/组分B-6/组分C-5(30％wt:5％wt:2％wt) 10.1
PEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 0.3
PEG100/组分B-1/组分C-1(30％wt:5％wt:2％wt) 0.8
4APEG25/组分B-1/组分C-1(30％wt:5％wt:2％wt) 0.6
4APEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 1.8
4APEG50/组分B-1/组分C-5(30％wt:5％wt:2％wt) 2.1
4APEG50/组分B-2/组分C-1(30％wt:5％wt:2％wt) 1.9
组分A-12/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.8
组分A-12/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 0.8
组分A-12/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 1.3
组分A-12/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 1.4
组分A-15/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.7
组分A-15/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 0.7
组分A-15/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 1.2
组分A-15/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 1.1
组分A-22/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.6
组分A-22/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 0.7
PEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.1
PEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.1
PEG100/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.3
PEG100/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.2
4APEG25/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.3
4APEG25/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.2
4APEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.4
4APEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.3
实施例二十二：光交联水凝胶韧性测试
通过拉伸测试得到水凝胶的应力应变曲线，韧性(断裂功)(MJ m -3)由拉伸应力应变曲线下方积分面积计算而来。拉伸性能测试采用GT-TCS-2000拉力机，拉伸测试样品为长20mm，宽3mm，厚2mm的哑铃型试样，测试速度为5mm/min。表5为实验组水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)和水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)，以及对照组水凝胶(30％4APEG50/5％组分B-1/2％组分C-1)和水凝胶(4％4APEG50/3％组分B-1/0.2％组分C-1)的韧性。从表5可以看出，实验组水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)和水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)韧性分别为11.8MJ m -3和1.2MPa；对照组水凝胶(30％4APEG50/5％组分B-1/2％组分C-1)和水凝胶(4％4APEG50/3％组分B-1/0.2％组分C-1)韧性为0.8MPa和0.21MPa。实验组水凝胶韧性分别是对照组的15倍和6倍，说明无论是高质量浓度还是低质量浓度，实验组水凝胶的韧性均显著高于对照组。其它不同配比的水凝胶韧性也均显著高于对照组，具体数据如表5所示。
表5
水凝胶材料组成 韧性(MJ m -3)
组分A-4/组分B-1/组分C-1(30％wt:5％wt:1％wt) 8.2
组分A-5/组分B-1/组分C-2(30％wt:5％wt:1％wt) 8.6
组分A-7/组分B-1/组分C-5(30％wt:5％wt:2％wt) 7.8
组分A-10/组分B-1/组分C-1(30％wt:5％wt:2％wt) 10.2
组分A-11/组分B-1/组分C-1(30％wt:5％wt:2％wt) 9.8
组分A-12/组分B-1/组分C-5(30％wt:5％wt:2％wt) 12.0
组分A-13/组分B-1/组分C-1(30％wt:5％wt:2％wt) 11.6
组分A-15/组分B-1/组分C-2(30％wt:5％wt:2％wt) 12.0
组分A-16/组分B-1/组分C-5(30％wt:5％wt:2％wt) 10.5
组分A-21/组分B-1/组分C-1(30％wt:5％wt:2％wt) 9.8
组分A-22/组分B-1/组分C-2(30％wt:5％wt:2％wt) 11.1
组分A-23/组分B-1/组分C-5(30％wt:5％wt:2％wt) 11.7
组分A-25/组分B-1/组分C-1(30％wt:5％wt:1％wt) 11.8
组分A-26/组分B-1/组分C-1(30％wt:5％wt:1％wt) 10.1
组分A-29/组分B-1/组分C-5(30％wt:5％wt:2％wt) 9.5
组分A-4/组分B-2/组分C-1(30％wt:5％wt:1％wt) 9.3
组分A-5/组分B-3/组分C-2(30％wt:5％wt:1％wt) 8.9
组分A-7/组分B-4/组分C-5(30％wt:5％wt:2％wt) 10.3
组分A-10/组分B-5/组分C-1(30％wt:5％wt:2％wt) 12.0
组分A-11/组分B-6/组分C-2(30％wt:5％wt:2％wt) 8.8
组分A-12/组分B-2/组分C-5(30％wt:5％wt:2％wt) 8.9
组分A-13/组分B-3/组分C-1(30％wt:5％wt:2％wt) 9.3
组分A-15/组分B-4/组分C-2(30％wt:5％wt:2％wt) 10.2
组分A-16/组分B-5/组分C-5(30％wt:5％wt:2％wt) 10.8
组分A-21/组分B-6/组分C-1(30％wt:5％wt:2％wt) 9.8
组分A-22/组分B-2/组分C-2(30％wt:5％wt:2％wt) 9.6
组分A-23/组分B-3/组分C-5(30％wt:5％wt:2％wt) 10.5
组分A-25/组分B-4/组分C-1(30％wt:5％wt:1％wt) 11.2
组分A-26/组分B-5/组分C-2(30％wt:5％wt:1％wt) 11.4
组分A-29/组分B-6/组分C-5(30％wt:5％wt:2％wt) 11.8
PEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 0.5
PEG100/组分B-1/组分C-1(30％wt:5％wt:2％wt) 0.7
4APEG25/组分B-1/组分C-1(30％wt:5％wt:2％wt) 0.8
4APEG50/组分B-1/组分C-1(30％wt:5％wt:2％wt) 1.2
4APEG50/组分B-1/组分C-5(30％wt:5％wt:2％wt) 1.8
4APEG50/组分B-2/组分C-1(30％wt:5％wt:2％wt) 1.6
组分A-12/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.7
组分A-12/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 0.7
组分A-12/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 1.1
组分A-12/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 1.2
组分A-15/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.6
组分A-15/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 0.7
组分A-15/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 1.2
组分A-15/组分B-1/组分C-5(4％wt:3％wt:0.2％wt) 1.1
组分A-22/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.6
组分A-22/组分B-1/组分C-5(3％wt:2％wt:0.2％wt) 0.6
PEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.02
PEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.03
PEG100/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.05
PEG100/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.10
4APEG25/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.15
4APEG25/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.18
4APEG50/组分B-1/组分C-1(4％wt:3％wt:0.2％wt) 0.21
4APEG50/组分B-1/组分C-1(3％wt:2％wt:0.2％wt) 0.19
实施例二十三：光交联水凝胶应用于创面封闭-组织免缝合
实验中，巴马小型猪表皮做3cm长伤口，清理创面，对齐创面，将600μL水凝胶前体溶液(4％组分A-15/3％组分B-1/0.2％组分C-1)均匀涂在伤口表面。然后，在395nm LED光源照射下，在皮肤创面处原位制备了水凝胶，实现了对组织的免缝合粘接。并同时对比 了空白，3-0手术缝线及该水凝胶的修复效果(图4)。10d时水凝胶组已经基本完全愈合，与缝线组与空白组相比明显减少了瘢痕产生，起到了良好的修复效果。
其他不同材料组成的水凝胶体系同样可以应用于创面封闭-组织免缝合。
实施例二十四：光交联水凝胶应用于创面封闭-皮肤修复
实验中，在巴马猪背部皮肤构造3*3cm的正方形皮肤全层缺损伤口。然后将1mL水凝胶前体溶液(4％组分A-15/3％组分B-1/0.2％组分C-1)填充到伤口部位。由于该溶液具有良好的流动性，伤口可以被水凝胶前体溶液充分填充和渗透。然后，在395nm LED光源照射下，在皮肤缺损处原位制备了水凝胶，实现了对创面的封闭(图5)。接下来，对比了光交联水凝胶，壳聚糖类凝胶和仅用凡士林油砂覆盖的巴马猪背部皮肤伤口在21天内的修复效果。光交联水凝胶伤口修复速率要明显快于其他两组，7d时就有明显的修复效果。
其他不同材料组成的水凝胶体系同样可以应用于创面封闭-皮肤修复。
实施例二十五：光交联水凝胶应用于创面封闭-宫颈切除术后促修复
实验中，在雌性新西兰白兔宫颈口处用电刀制造缺损伤口。将两个宫颈口分为两组进行处理。一组为将水凝胶前体溶液(3％组分A-22/2％组分B-1/0.2％组分C-1)涂抹到伤口部位，然后，在395nm LED光源照射下，将水凝胶前体溶液完全固化成水凝胶，实现了对创面的封闭。另一侧不做处理。观察宫颈口在7天内的修复效果。如图所示，左侧宫颈口为水凝胶组，右侧宫颈口为空白组，其中光交联水凝胶伤口修复速率要明显快于空白组，创面已完全愈合，而空白组仍有充血(图6)。
其他不同材料组成的水凝胶体系同样可以应用于创面封闭-宫颈切除术后促修复。
实施例二十六：光交联水凝胶应用于创面封闭-痔疮切除术后促修复
实验中，在巴马猪肛门处用电刀制造缺损伤口，伤口对称位于肛门两侧。一组为将水凝胶前体溶液(3％组分A-12/2％组分B-1/0.2％组分C-1)涂抹到伤口部位，然后，在395nm LED光源照射下，将水凝胶前体溶液完全固化成水凝胶，实现了对创面的封闭。另一侧不做处理。观察肛门伤口在7天内的修复效果。如图所示，左侧为空白组，右侧为凝胶组，其中光交联水凝胶伤口修复速率要明显快于空白组，7天后创面已完全愈合，而空白组仍有创面(图7)。
其他不同材料组成的水凝胶体系同样可以应用于创面封闭-痔疮切除术后促修复。
实施例二十七：光交联水凝胶应用于创面封闭-腹腔术后防黏连
实验中，采用SD大鼠构建腹壁-盲肠刮擦的腹腔黏连模型。由于盲肠是腹腔内最粗、通路最多，血管分布最丰富的肠段，当其对应的腹壁同时发生损伤并且不采取措施的前提下发生腹腔黏连的概率极大，构造的黏连模型稳定。在手术过程中，水凝胶前体溶液(4％组分A-15/3％组分B-1/0.2％组分C-1)可以充分的覆盖盲肠和腹壁的伤口，并且在垂直的组织面上有充足的驻留时间至其光照成胶。在给予30s光照后，得到的水凝胶固定在了创伤部位，利用外科手术刀片对其施加一定的力的情况下并不能将该水凝胶从创伤部位剥离。上述从水凝胶前体溶液的给予到完全成胶的过程在1min内可以结束。手术后，在无菌的环境下饲养上述SD大鼠14天。14d后，再次打开SD大鼠的腹腔，对其腹腔黏连 情况进行了记录(图8，其中a为对照组，b为实验组)。在水凝胶处理的实验组的10只大鼠中，有8只大鼠14d后没有出现任何的肠-腹壁，肠-肠之间的黏连；1只大鼠出现了中等程度的腹壁与盲肠之间的黏连；1只大鼠出现了肠与肠之间一点薄层黏连。另外，上述9只没有发生肠-腹壁黏连的SD大鼠中看不见任何的水凝胶残留，腹壁上的伤口完全愈合。对照组的10只大鼠都发生了严重的腹壁和盲肠的黏连。接下来对实验组和对照组手术中伤口部位的组织切片通过H&E染色的方式进行了组织学分析。实验组中的SD大鼠14d后盲肠和腹壁的损伤基本完全恢复，表层已经再上皮化。而对照组中的SD大鼠14d后盲肠的平滑肌同腹壁的肌肉组织完全融合，成纤维细胞和炎症细胞在黏连处沉积。
其他不同材料组成的水凝胶体系同样可以应用于创面封闭-腹腔术后防黏连。
实施例二十八：光交联水凝胶应用于创面封闭-声带术后防黏连
实验中，采用比格犬声带受损黏连模型。通过喉镜手术方式用电刀将两侧声带破坏。实验组中，用水凝胶前体溶液(4％组分A-15/3％组分B-1/0.2％组分C-1)充分的覆盖受损声带，并用395nm光光照30s至完全成胶。空白组不做处理。14d后，再次观察比格犬声带，对其黏连情况进行了记录。如图9所示，在水凝胶处理的实验组中，14d后只有将近四分之一声带有粘连。而对照组的比格犬声带有一半处于黏连。接下来对实验组和对照组手术中伤口部位的组织切片通过H&E染色的方式进行了组织学分析。实验组中的比格犬声带的损伤基本完全恢复，表层已经再上皮化。而对照组中的比格犬声带中成纤维细胞和炎症细胞在黏连处沉积。
其他不同材料组成的水凝胶体系同样可以应用于创面封闭-声带术后防黏连。
实施例二十九：光交联水凝胶应用于创面封闭-口腔溃疡
实验中，在SD大鼠口腔构造直径1.0cm的口腔溃疡缺损伤口。然后将200μL水凝胶前体溶液(4％组分A-15/3％组分B-1/0.2％组分C-1)填充到伤口部位。由于该溶液具有良好的流动性，伤口可以被水凝胶前体溶液充分填充和渗透。然后，在395nm LED光源照射下，在口腔缺损处原位制备了水凝胶，实现了对口腔创面的封闭。接下来，对比原位成型的水凝胶和仅用生理盐水清洗处理的SD大鼠口腔伤口在5天内的修复效果，对实验组和对照组手术中伤口部位的组织切片通过H&E染色的方式进行了组织学分析(图10)。原位成型的水凝胶伤口修复速率要明显快于对照组，5d时粘膜基本恢复正常水平；没有水凝胶填充的伤口修复速率明显慢一些，说明了该光交联水凝胶作为细胞支架材料对口腔溃疡修复具有促进作用。
其他不同材料组成的水凝胶体系同样可以应用于创面封闭-口腔溃疡。
实施例三十：光交联水凝胶应用于组织渗液封堵-肠漏封堵
采用新西兰雄性大白兔，分为两组进行盲肠渗漏封堵实验：a：水凝胶处理(4％组分A-15/3％组分B-1/0.2％组分C-1)组；b：不做处理的对照组。实验中，在兔子盲肠处制造渗漏的模型，然后将水凝胶前体溶液涂抹到伤口处，待充分渗透后光照原位成胶，成胶后水凝胶能牢固的黏附在缺损处，不需要额外的固定。在手术4周后，通过静脉注射空气的方法处死实验中的兔子，并提取盲肠对实验修复效果进行评价。结果显示，使用水凝胶封堵的盲肠没有发生渗漏的情况，而没用水凝胶处理的盲肠发生了严重的渗漏。经过几周 的修复，原来盲肠有缺损的部位经水凝胶处理过后得到了明显的修复，因此，该水凝胶不仅能够有效封堵渗漏，还有利于术后受损组织的修复。
其他不同材料组成的水凝胶体系同样可以应用于渗液封堵-肠漏封堵。
实施例三十一：光交联水凝胶应用于组织渗液封堵-胃漏封堵
采用SD大鼠，分为三组进行胃部组织免缝合实验：a：水凝胶处理(4％组分A-15/3％组分B-1/0.2％组分C-1)组；b：不做处理的对照组；c:3-0手术缝合线缝合。实验中，在大鼠胃部制造伤口的模型，然后将水凝胶前体溶液涂抹到伤口处，待充分渗透后光照原位成胶，成胶后水凝胶能牢固的黏附在缺损处，不需要额外的固定。缝线组选用3-0手术线缝合。术后10天，安乐死处死SD大鼠，并提取胃部对实验结果进行评价。结果显示，使用水凝胶封堵的胃部完好，没有发生渗漏的情况，缝线组胃部完好，而没作处理组的大鼠在术后一天均死亡。经过十天的修复，原来胃部有缺损的部位经水凝胶处理过后得到了明显的修复，因此，该水凝胶不仅能够有效封堵渗漏，还有利于术后受损组织的修复。
其他不同材料组成的水凝胶体系同样可以应用于组织渗液封堵-胃漏封堵。
实施例三十二：光交联水凝胶应用于止血材料-肝脏止血
采用SD大鼠，对水凝胶的止血效果进行评价，分为两组进行肝脏止血实验：a：水凝胶处理(4％组分A-15/3％组分B-1/0.2％组分C-1)组；b空白对照组。实验大鼠通过水合氯醛(4％水溶液)腹腔注射进行麻醉，注射计量为0.9ml/100g，深度麻醉后，用剃毛器将大鼠前胸部位毛剃光，碘酒消毒。然后沿着腹腔中线切开大约4cm长切口，打开腹腔，暴露肝脏部位。在肝脏左叶做一约2cm切口。a组在切口处加水凝胶前体溶液覆盖切面，395nm LED光照1min成胶止血；b组不做任何处理，让肝脏切口渗血自然凝固，用纱布吸去渗血，通过减重法记录出血量，和出血时间(图11)。实验结束后，a组水凝胶在切口原位交联并将切面伤口隔离，将肝脏放回腹腔，缝合。b组不做处理直接缝合。14d后，观察SD大鼠肝脏恢复情况，通过腹腔注射过量麻醉剂水合氯醛(4％水溶液，2.7ml/100g)处死大鼠，沿胸腔中线打开腹腔，观察三组大鼠肝脏恢复情况，并拍照记录。同时对肝脏损伤部位组织取样，标本用4％福尔马林溶液固定2d，脱水处理后，石蜡包埋，在用切片机进行组织切片操作，样片厚度5μm。最后对标本进行H&E染色，用光学显微镜拍照观察记录。实验结果显示，a组肝脏恢复良好，水凝胶降解完全，未发生粘连，肝脏切口长出新生肝脏组织。b组普遍存在肝脏与网膜粘连的情况。H&E染色显示实验组肝脏表面光滑圆润，有丰富的血管分布，肝脏界面清晰。而发生粘连的肝脏经H&E染色发现肝脏界面凹凸不平，肝脏与网膜组织粘连在一起，界面处有沉积的炎症细胞。
其他不同材料组成的水凝胶体系同样可以应用于止血材料-肝脏止血。
实施例三十三：光交联水凝胶应用于止血材料-肾脏止血
采用新西兰白兔，对水凝胶的止血效果进行评价，分为两组进行肾脏止血实验：a：水凝胶处理(3％组分A-22/2％组分B-1/0.2％组分C-5)组；b空白对照组。实验新西兰白兔深度麻醉后，用剃毛器将新西兰白兔侧腹部位毛剃光，碘酒消毒。然后沿着侧腹部切开大约5cm长切口，打开腹腔，暴露肾脏部位。在肾脏做一直径约1cm，深度约3mm的 圆形损伤切口。a组在切口处加水凝胶前体溶液覆盖切面，395nm LED光照1min成胶止血；b组不做任何处理，用纱布吸去渗血。实验结束后，a组水凝胶在切口原位交联并将切面伤口隔离，将肾脏放回腹腔，缝合。b组不做处理直接缝合。几小时后，空白组新西兰白兔失血死亡，而凝胶组新西兰白兔止血完全，无异常反应(图12)。
其他不同材料组成的水凝胶体系同样可以应用于止血材料-肾脏止血。
实施例三十四：光交联水凝胶应用于止血材料-脾脏止血
采用比格犬，对水凝胶的止血效果进行评价，分为三组进行脾脏止血实验：a：明胶海绵组；b：水凝胶处理((4％组分A-15/3％组分B-1/0.2％组分C-1))组；c阳性对照组。实验比格犬通过巴比妥类麻醉剂进行肌肉注射麻醉，注射计量为0.5ml/kg，深度麻醉后，用剃毛器将比格犬侧腹部位毛剃光，碘酒消毒。然后沿着侧腹部切开大约10cm长切口，打开腹腔，暴露脾脏部位。在脾脏做一直径8mm的切口。a组用明胶海绵进行止血；b组在切口处加水凝胶前体溶液覆盖切面，395nm LED光照1min成胶止血；c组不做任何处理，让脾脏伤口渗血自然凝固，用纱布吸去渗血，通过减重法记录出血量，和出血时间。实验结束后，a组将粘附在切面的明胶海绵一并留在比格犬体内进行缝合。b组水凝胶在切口原位交联并将切面伤口隔离，将脾脏放回腹腔，缝合。c组不做处理直接缝合。14d后，观察比格犬脾脏恢复情况，通过肌肉注射过量麻醉剂巴比妥类麻醉剂处死比格犬，沿腹腔侧部打开腹腔，观察三组比格犬脾脏恢复情况，并拍照记录。同时对脾脏损伤部位组织取样，标本用4％福尔马林溶液固定2d，脱水处理后，石蜡包埋，在用切片机进行组织切片操作，样片厚度5μm。最后对标本进行H&E染色，用光学显微镜拍照观察记录。实验结果显示，b组脾脏恢复良好，水凝胶降解完全，未发生粘连，脾脏伤口长出新生脾脏组织。a组比格犬体内明胶海绵仍未降解，并且比格犬普遍器脏与网膜粘连严重。c组普遍存在脾脏与网膜粘连的情况。H&E染色显示实验组脾脏表面光滑圆润，有丰富的血管分布，脾脏界面清晰。而发生粘连的脾脏经H&E染色发现脾脏界面凹凸不平，脾脏与网膜组织粘连在一起，界面处有沉积的炎症细胞。
其他不同材料组成的水凝胶体系同样可以应用于止血材料-脾脏止血。
实施例三十五：光交联水凝胶应用于止血材料-骨断面止血
采用新西兰雄性大白兔，分为三组进行骨断面止血实验：a：水凝胶处理(4％组分A-15/3％组分B-1/0.2％组分C-1)组；b：骨蜡处理组；c：不做处理的对照组。实验中，在兔子股骨制造骨断面出血模型，a组是将水凝胶前体溶液涂抹到伤口处，待充分渗透后光照原位成胶，实现对骨断面出血的有效封堵，由于该水凝胶优异的组织粘附力及光固化速度，能够起到及时、有效的止血效果；b组是用常规的骨蜡处理出血伤口；c组是对出血伤口不做处理。在手术8周后，通过静脉注射空气的方法处死实验中的兔子，并取样对实验修复效果进行评价。结果显示，使用水凝胶处理的伤口有较好的止血效果，基本与骨蜡组的效果差不多，而不做处理的伤口会有持续的出血状况。经过2周的修复，原来伤口出血部位经水凝胶处理过后组织得到了明显的修复，而经骨蜡处理的伤口没有得到修复，主要是由于骨蜡在体内不降解，因此，该水凝胶不仅能够有效实现骨断面止血，还有利于术后受损组织的修复。
其他不同材料组成的水凝胶体系同样可以应用于止血材料-骨断面止血。
实施例三十六：光交联水凝胶应用于止血材料-心脏止血
采用比格犬，用10mL注射器针头造成心脏出血模型。分为三组进行心脏止血实验：a：水凝胶处理(3％组分A-12/2％组分B-1/0.2％组分C-1)组；b：纤维蛋白原胶处理组；c：不做处理的对照组。a组是将水凝胶前体溶液涂抹到伤口处，用395nm光光照原位成胶，实现对心脏出血的有效封堵，由于该水凝胶优异的组织粘附力及光固化速度，能够起到及时、有效的止血效果；b组是用纤维蛋白原胶处理出血伤口；c组是对出血伤口不做处理。后两组因为止血材料粘附力差，胶本身强度不够，均不能达到肺动脉出血的止血效果。而光交联水凝胶组因为其优异的组织粘附力和强度，可以快速止住心脏出血(图13)。
其他不同材料组成的水凝胶体系同样可以应用于止血材料-心脏止血。
实施例三十七：光交联水凝胶应用于疝气补片的固定
采用SD大鼠，分为两组进行疝气补片固定实验：a：水凝胶固定(水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)组；b：缝线组。实验中，在SD大鼠腹部做边长3cm的正方形缺口，a组是用水凝胶前体溶液涂在补片上，待充分渗透后光照原位成胶，实现固定补片的作用；b组是用缝线方法固定补片。在手术2周后，通过腹腔注射麻醉剂处死大鼠，并取样对实验修复效果进行评价(图14左侧为b组，右侧为去a组)。结果显示，使用水凝胶固定的补片完好固定，并有包膜在补片与组织接触位置生成，将补片包裹在里面。
其他不同材料组成的水凝胶体系同样可以应用于疝气补片的固定。
实施例三十八：光交联水凝胶应用于翼状胬肉术后结膜瓣的固定
采用新西兰雄性大白兔，分为两组进行翼状胬肉术后结膜瓣的固定实验：a：水凝胶固定(3％组分A-12/2％组分B-1/0.2％组分C-1)组；b：缝线组。实验中，在兔子眼睛上取下一块结膜瓣，a组是将水凝胶前体溶液涂抹到伤口处，待充分渗透后覆盖结膜瓣并光照原位成胶，实现结膜瓣的固定粘接；b组是用缝线固定结膜瓣。在手术2周后，通过静脉注射空气的方法处死实验中的兔子，并取样对实验修复效果进行评价。结果显示，使用水凝胶处理的伤口与缝线组恢复效果相同。经过2周的修复，结膜瓣与虹膜完全贴附在一起，与周围结膜组织无区别。
其他不同材料组成的水凝胶体系同样可以应用于翼状胬肉术后结膜瓣的固定。
实施例三十九：光交联水凝胶材料应用于心脏贴片
采用SD大鼠，分为两组进行心脏贴片的试验。a组为心肌梗死模型组，b组为水凝胶贴片(30％组分A-26/5％组分B-1/1％组分C-1)组。手术前老鼠应用戊巴比妥钠(60mg/kg)腹腔麻醉，应用小动物喉镜经口腔气管插管，然后用小动物呼吸机(深圳瑞沃德，407)正压通气，呼吸频率70次/分，潮气量2.5ml/次。用肢体导联进行心电图监测。在左胸第5肋骨平面做竖直切口，分离肌肉，用止血钳刺破胸膜暴露心脏。小心撕开心包，将心脏挤出胸腔后，以5-0带针缝合线于左心耳下缘2mm处结扎左冠状动脉前降支；结扎成功的标志是Ⅱ导联心电图S-T段抬高及结扎部位以下心肌颜色泛白。在左心室前壁涂抹水凝胶，然后用紫外光照射至完全成胶。对假心肌梗死组大鼠进行同样手术 过程，仅穿线不结扎冠状动脉。将心脏放入胸腔内，逐层缝合。术后一个月采用苏木精-伊红及马松三色染色法评价心梗后心室重构的情况。通过结果可以看出水凝胶组经过心室壁机械治疗后能减少心室扩张，心室收缩功能较MI组提高。在8周后对心梗区域还进行了组织学分析，空白组显示心室壁梗死区域显著变薄，局部结构紊乱。而水凝胶组梗死区室壁稍变薄，心室腔结构相对完整(图15)。Masson染色结果显示空白组显示大量的胶原纤维替代心肌组织，结构紊乱，而水凝胶组心室壁仅有少量的胶原纤维。这些结果表明，心肌梗死后立即应用水凝胶可大大减少心肌细胞死亡及损伤区域纤维化组织的继发性替代。水凝胶提供的力学支持对急性心肌梗死后的病理性心脏重构具有显著的逆转作用。该实验结果为今后的心肌梗塞的治疗提供新的思路。
其他不同材料组成的水凝胶体系同样可以应用于心脏贴片。
实施例四十：光交联水凝胶应用于组织工程支架材料-软骨修复
采用新西兰雄性大白兔，分为三组进行关节软骨的修复实验：a：包裹有软骨细胞的水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)组，即Gel+软骨细胞组；b：单纯的水凝胶(4％组分A-15/3％组分B-1/0.2％组分C-1)组，即Gel组；c：不做处理的对照组，即Control组。在实验中，该水凝胶前体溶液可以充分的渗透并且填充兔子关节软骨的缺损处，光照成胶后牢固的黏附在缺损处，不需要额外的固定。在手术12周后，通过静脉注射空气的方法处死实验中的兔子，并提取损伤关节对实验修复效果进行评价。兔子关节软骨损伤处大体观照片结果显示，12周后Gel+软骨细胞组在关节缺损处长出了光滑的新生软骨组织，同时和旧的软骨组织进行了良好的整合；在Gel组中软骨也进行了一定的修复，但是还可以看出手术时软骨创伤的轮廓；而在Control组中，软骨组织基本没有修复的情况，损伤处还是明显的空洞。接下来，我们进一步利用H&E染色的方法评价了上述各组软骨的修复情况。H&E染色结果显示，Gel+软骨细胞组和Gel组都有新生的组织生成并且同旧的软骨组织整合良好；但是Gel+软骨细胞组的新生组织的厚度要好于Gel组，并且表面平整；而在Control组中难以找到明显新生组织的迹象。另外，采用番红-O和免疫组化染色的方法对新生软骨的成分进行了分析。在Gel+软骨细胞组和Gel组中，新生的软骨组织都表现出了番红-O染色活性，证明该新生的软骨组织内含有正常软骨的糖蛋白成分。同时，Gel+软骨细胞组和Gel组的新生软骨组织都表现出II型胶原的染色活性，证明该软骨组织中含有大量的II型胶原。上述番红-O和免疫组化染色结果证明利用新型光交联水凝胶材料进行软骨修复时，新生的软骨组织是透明软骨。
其他不同材料组成的水凝胶体系同样可以应用于组织工程支架材料-软骨修复。
实施例四十一：光交联水凝胶应用于组织工程支架材料-骨修复
采用SD大鼠，进行颅骨修复实验，并将上述SD大鼠随机分成3组：a：水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)+羟基磷灰石的实验组；b：水凝胶处理(30％组分A-25/5％组分B-1/1％组分C-1)组；c：不用材料处理的对照组。实验中，用4％的水合氯醛溶液(0.9mL每克体重)对其进行腹腔麻醉，碘酒消毒。然后，利用外科手术刀片打开大鼠颅骨处头皮。利用牙环钻在老鼠颅骨左右处对称制造直径5mm的完全颅骨缺损模型。在实验组中，取200μL的水凝胶前体溶液填充到SD大鼠颅骨缺损处，使其充分向 伤口边缘渗透；用395nm LED光源(20mW/cm 2)光照30s使其完全成胶；最后用缝合线缝合老鼠的头皮。在对照组中，制造好SD大鼠颅骨缺损模型后，直接缝合头皮，不做其他任何处理。上述SD大鼠在无菌，37℃的环境中饲养8周的时间。然后，利用micro-CT扫描成像的方式对各组中SD大鼠颅骨的修复情况进行了评价。结果显示，在没有进行任何处理的对照组中，SD大鼠的颅骨缺损基本没有进行任何的修复，而用水凝胶填充的颅骨缺损处边缘有新生的成骨形成，但是新生骨组织的量较少，大部分缺损处并没有得到良好的修复，而用水凝胶+羟基磷灰石填充的颅骨缺损处基本得到了修复，大量的新生骨组织在缺损处形成。接着利用Van Gieson染色法对颅骨的组织切片进行了组织学染色分析。结果显示，水凝胶+羟基磷灰石处理的SD大鼠的颅骨缺损处都长出了完整的新生骨组织，而只用水凝胶处理的颅骨缺损处只有少量新生骨组织生成，大部分缺损处的骨组织依旧是缺损状态，在对照组中，几乎没有新生的骨组织生成。该组织染色结果进一步证实了包裹有羟基磷灰石的水凝胶对骨缺损有良好的修复效果。
其他不同材料组成的水凝胶体系同样可以应用于组织工程支架材料-骨修复。
实施例四十二：光交联水凝胶应用于3D打印(FDM)的生物墨水
3D打印技术是近些年来迅速发展的一种三维成型技术，已被广泛应用，目前3D打印技术包括熔融沉积式(FDM)、光固化成型(SLA)、激光烧结式(SLS)、连续液面制造式(CLIP)等。但是适用于带细胞打印的方式目前主要是FDM的方式，带细胞打印的材料主要是水凝胶材料，因此，发展3D打印的生物墨水-可打印的水凝胶材料以及提高水凝胶材料打印的分辨率是该领域研究的基本问题。以水凝胶(3％组分A-22/2％组分B-1/0.2％组分C-1)为例，将一定质量浓度的水凝胶前体溶液均匀混合细胞后，装入低温打印桶中，控制打印温度在25℃左右，通过温度来调整生物墨水的粘稠度，以获得最佳的打印状态，然后确定合适的打印压力和打印速度，进行不同结构的生物打印，打印完成后通过光照交联水凝胶(或是边打印边光照)，从而获得带细胞且带结构的水凝胶，进行3D细胞培养。
实施例四十三：光交联水凝胶应用于3D打印(DLP)的生物墨水
DLP(数字光处理)3D打印技术是近来年发展起来的一种新型的光固化打印方式，相比于SLA(立体光固化成型)式的打印机，DLP以其打印速度快、分辨率高而具有大多数打印方式所不可比拟的优势，目前在牙科模型、珠宝设计等领域已经具备一定的应用前景。但是，当前市场上使用的打印墨水仅限于光固化树脂，而水凝胶作为一种新兴的生物墨水还没有得到广泛的关注，主要是由于没有适合DLP打印的水凝胶材料，而本发明提出的复合型光交联水凝胶材料以其快的光固化速度，优异的机械性能非常适合于3D打印，而且具有更高的打印精度。以水凝胶组分(3％A-11/2％组分B-1/0.2％组分C-1)为例，将一定质量浓度的水凝胶前体溶液装入液体槽中，通过控制光源的强弱、曝光时间等参数来调整生物墨水的打印情况，以获得最佳的打印状态，从而得到了带结构的3D打印水凝胶(图16)。
其他不同材料组成的水凝胶体系同样可以应用于3D打印(DLP)的生物墨水。
实施例四十四：光交联水凝胶应用于药物的包裹与释放
水凝胶是一种能够在水中溶胀但不溶解的交联高分子网络，由于水凝胶大部分由水组成，因此具有非常好的生物相容性，特别适用于药物和生物活性大分子的载体。包裹于水凝胶材料中的药物或生物活性大分子通过分子的扩散作用和材料的降解作用实现药物持续释放的效果。以药物包裹与释放为例具体介绍如下：以水凝胶(30％组分A-25/5％组分B-1/1％组分C-1)为例，将其溶于生理盐水中，配成一定质量浓度的水凝胶前体溶液，加入一定量的药物分子，取200μL上述溶液置于圆形模具中光照成水凝胶，接着放入24孔细胞培养板中，加入一定量的生理盐水进行药物释放实验，通过紫外测试分析溶液中药物的释放量，以此来评价该材料对药物的释放效果。
其他不同材料组成的水凝胶体系同样可以应用于药物的包裹与释放。
上述的对实施例的描述是为便于该技术领域的普通技术人员能理解和使用发明。熟悉本领域技术的人员显然可以容易地对这些实施例做出各种修改，并把在此说明的一般原理应用到其他实施例中而不必经过创造性的劳动。因此，本发明不限于上述实施例，本领域技术人员根据本发明的揭示，不脱离本发明范畴所做出的改进和修改都应该在本发明的保护范围之内。

Claims (25)

  1. 邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，具有式I结构：
    Figure PCTCN2020106113-appb-100001
    其中，R’选自氢、卤原子、羟基、巯基、胺基、硝基、氰基、醛基、酮基、酯基、酰胺基、膦酸基、膦酸酯基、磺酸基、磺酸酯基、砜基、亚砜基、芳基、杂芳基、烷基、亚烷基、改性烷基或改性亚烷基，
    R”选自C、N、O或S；
    R 1选自氢、醚键类取代基、酯键类取代基、碳酸酯键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基，
    R 2，R 3，R 4，R 5独立地选自氢、卤原子、羟基、巯基、胺基、硝基、氰基、醛基、酮基、酯基、酰胺基、膦酸基、膦酸酯基、磺酸基、磺酸酯基、砜基、亚砜基、芳基、杂芳基、烷基、亚烷基、改性烷基或改性亚烷基；
    式I中，P 1与R 2，R 3，R 4，R 5中任意的一个或多个基团相连接；
    式I中，n≥2，
    式I中，P 1为一种亲水或水溶性的多臂聚乙二醇或其衍生物，P 1具有以下通式：
    Figure PCTCN2020106113-appb-100002
    式II中，PEG为单链聚乙二醇，
    式II中，X，Y独立地选自聚乙二醇、聚丙二醇、聚乳酸、聚酯、聚羟基乙酸、聚乙烯醇、聚氨基酸、聚丙烯酸、聚甲基丙烯酸、聚丙烯酰胺、聚甲基丙烯酰胺、聚乙烯吡咯烷酮，或各种亲水性单体与亲水性单体、亲水性单体与疏水性单体、疏水性单体与疏水性单体的共聚物；
    式II中，m≥1，R 6为多臂支化中心，支化度为2-8。
  2. 根据权利要求1所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，式II中连接R 6结构部分分子量不小于6000。
  3. 根据权利要求1所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，式II中，R 6选自以下两臂支化中心、三臂支化中心、四臂支化中心、五臂支化中心、六臂支化中心、八臂支化中心中一种或两种以上的组合：
    其中两臂支化中心包括以下结构：
    Figure PCTCN2020106113-appb-100003
    其中三臂支化中心包括以下结构：
    Figure PCTCN2020106113-appb-100004
    其中四臂支化中心包括以下结构：
    Figure PCTCN2020106113-appb-100005
    其中五臂支化中心包括以下结构：
    Figure PCTCN2020106113-appb-100006
    其中六臂支化中心包括以下结构：
    Figure PCTCN2020106113-appb-100007
    其中八臂支化中心包括以下结构：
    Figure PCTCN2020106113-appb-100008
  4. 根据权利要求1所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，式I中，P 1选自两臂聚乙二醇、三臂聚乙二醇、四臂聚乙二醇、六臂聚乙二醇或八臂聚乙二醇；
    进一步优选地，P 1为20000分子量以上的两臂聚乙二醇或40000分子量以上的四臂聚乙二醇。
  5. 根据权利要求1所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，式I中，R 2，R 3，R 4，R 5中至少两个相互连接，与碳原子一起形成饱和或不饱和的脂环或脂杂环，或形成芳环或芳杂环。
  6. 根据权利要求5所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，当式I结构中R 2，R 3，R 4，R 5中至少两个相互连接，与碳原子一起形成饱和或不饱和的脂环或脂杂环，或形成芳环或芳杂环时，P 1还可以连接于R 2，R 3，R 4，R 5之间形成的饱和或不饱和脂环或脂杂环，或形成的芳环或芳杂环。
  7. 根据权利要求1或5或6所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，对于P 1与R 2，R 3，R 4，R 5中任意的一个或多个基团相连接，或连接于R 2，R 3，R 4，R 5之间形成的饱和或不饱和脂环或脂杂环，或形成的芳环或芳杂环上时，连接 键选自P 1-O-,P 1-S-,P 1-NH-,P 1-CH-,P 1-COO-,P 1-CONH-，该连接键的一端与P 1相连，另一端连接在式I所示分子的苯环上。
  8. 根据权利要求1所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，所述烷基为具有1～30个碳原子的饱和或不饱和脂肪族直链或支链的烷基；
    所述亚烷基为具有1～30个碳原子的饱和或不饱和脂肪族直链或支链的亚烷基；
    所述改性烷基为烷基的任意碳原子被选自卤原子、-OH、-SH、-NO 2、-CN、-CHO、-COOH、酯基、酰胺基、芳基、亚芳基、-CO-、-O-、-S-、-SO-、-SO 2-、伯胺基、仲胺基、叔胺基、季铵盐基、饱和或不饱和的单环或双环亚环烃基、桥联脂杂环中的至少一种基团置换所得的基团，所述改性烷基具有1～30个原子，其碳碳单键可任意地被碳碳双键或碳碳叁键替换；
    所述改性亚烷基为亚烷基的任意碳原子被选自卤原子、-OH、-SH、-NO 2、-CN、-CHO、-COOH、酯基、酰胺基、芳基、亚芳基、-CO-、-O-、-S-、-SO-、-SO 2-、伯胺基、仲胺基、叔胺基、季铵盐基、饱和或不饱和的单环或双环亚环烃基、桥联脂杂环中的至少一种基团置换所得的基团，所述改性亚烷基具有1～30个原子，其碳碳单键可任意地被碳碳双键或碳碳叁键替换；
    所述醚键类取代基选自以下结构：
    -(CH 2) xOCH 3、-(CH 2CH 2O) xCH 3、-(CH 2) x(CH 2CH 2O) yCH 3、或
    Figure PCTCN2020106113-appb-100009
    其中x和y≥0且为整数；
    所述酯键类取代基选自以下结构：
    -OCO(CH 2) xCH 3、-OCO(CH 2CH 2O) xCH 3、-OCO(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    所述碳酸酯键类取代基选自以下结构：
    -OCOO(CH 2) xCH 3、-OCOO(CH 2CH 2O) xCH 3、-OCOO(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    所述胺基甲酸酯键类取代基选自以下结构：
    -OCONH(CH 2) xCH 3、-OCONH(CH 2CH 2O) xCH 3、-OCONH(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    所述巯基甲酸酯键类取代基选自以下结构：
    -OCOS(CH 2) xCH 3、-OCOS(CH 2CH 2O) xCH 3、-OCOS(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    所述磷酸酯键类取代基选自以下结构：
    -POOO(CH 2) xCH 3、-POOO(CH 2CH 2O) xCH 3、-POOO(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    所述芳基为5～10元芳香单环或芳香稠合双环结构；
    所述杂芳基为环上含有选自O、S、N或Si中的至少一种杂原子的5～10元芳香单环或芳香稠合双环结构；
    所述卤原子各自独立地选自F、Cl、Br、I；
    所述脂环为饱和或不饱和的3～10元单环或多环脂环；
    所述脂杂环为环上含有选自O、S、N或Si中的至少一种杂原子的饱和或不饱和的3-10元单环或多环脂杂环，所述脂杂环上含有S原子时，其任选为-S-、-SO-或-SO 2-；所述脂环或脂杂环上的H还可任意地被卤原子、硝基、芳基、烷基或改性烷基取代；
    所述芳环为5～10元芳香单环或芳香稠合双环；
    所述芳杂环为环上含有选自O、S、N或Si中的至少一种杂原子的5～10元芳香单环或芳香稠合双环；所述芳环或芳杂环上的H还可任意地被卤原子、硝基、芳基、烷基或改性烷基取代。
  9. 根据权利要求8所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，
    烷基类取代基选自直链烷基-(CH 2) xCH 3、支链烷基-(CH 2) x(CY’Y”) yCH 3，Y’，Y”为氢、烷基或改性烷基，其中x和y≥0且为整数；
    醚类取代基选自-O(CH 2) xCH 3、-O(CH 2CH 2O) xCH 3、-O(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    硫醚类取代基选自-S(CH 2) xCH 3、-S(CH 2CH 2O) xCH 3、-S(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    胺基类取代基选自-NH(CH 2) xCH 3、-NH(CH 2) x(CY’Y”) yCH 3、-N(CY’Y”) x(CY’Y”) y、
    Figure PCTCN2020106113-appb-100010
    (Y’，Y”为氢、烷基或改性烷基)，其中x和y≥0且为整数；
    酯类取代基选自-COO(CH 2) xCH 3、-COO(CH 2CH 2O) xCH 3、-COO(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    酰胺类取代基选自-CONH(CH 2) xCH 3、-CONH(CH 2CH 2O) xCH 3、-CONH(CH 2) x(CH 2CH 2O) yCH 3，其中x和y≥0且为整数；
    芳香族类取代基选自-Ph、
    Figure PCTCN2020106113-appb-100011
    脂环或脂杂环选自
    Figure PCTCN2020106113-appb-100012
    芳环或芳杂环选自：
    Figure PCTCN2020106113-appb-100013
  10. 根据权利要求1所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在 于，R’选自：
    -H、-CH 3、-CH 2CH 3、-CH＝CH-CH＝CH-CH 3、-F、-Cl、-Br、-I、-CF 3、-CCl 3、-CBr 3、-CI 3、-CN、-COOH、-Ph、
    Figure PCTCN2020106113-appb-100014
    R 2，R 3，R 4，R 5独立的选自：
    -H、-OH、-SH、-NH 2、-F、-Cl、-Br、-I、-CF 3、-CCl 3、-CBr 3、-CI 3、-NO 2、-CN、-CHO、-COOH、-COONH 2、-SO 3H。
  11. 根据权利要求1所述邻硝基苄基类光扳机修饰的光敏高分子衍生物，其特征在于，所述式I可选自以下组分A-1～组分A-30中的结构：
    Figure PCTCN2020106113-appb-100015
    Figure PCTCN2020106113-appb-100016
    Figure PCTCN2020106113-appb-100017
    Figure PCTCN2020106113-appb-100018
  12. 高强度和韧性的光交联水凝胶材料，其特征在于，由以下三种组分为原料制备而成：
    如权利要求1-11中任一项所述的邻硝基苄基类光扳机修饰的光敏高分子衍生物；
    双键官能团修饰的高分子衍生物；
    光引发剂。
  13. 根据权利要求12所述高强度和韧性的光交联水凝胶材料，其特征在于，所述双键官能团修饰的高分子衍生物，具有式III所示结构：
    Figure PCTCN2020106113-appb-100019
    式III中，R 1’，R 2’、R 3’独立地选自氢、卤原子、芳环、杂芳环、脂环、脂杂环、烷基或改性烷基；R 4’选自烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基；
    n≥2；
    P 1’为一种亲水或水溶性天然高聚物或合成高聚物，或P 1’独立的选自多种亲水或水溶性天然高聚物或合成高聚物。
  14. 根据权利要求13所述高强度和韧性的光交联水凝胶材料，其特征在于，式III中卤原子、芳环、杂芳环、脂环、脂杂环、烷基、改性烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基的定义与式I中卤原子、芳环、杂芳环、脂环、脂杂环、烷基、改性烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基的定义相同，式III中卤原子、芳环、杂芳环、脂环、脂杂环、烷基、改性烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基的选择可以不同于式I。
  15. 根据权利要求13所述高强度和韧性的光交联水凝胶材料，其特征在于，所述亲水或水溶性天然高聚物包括天然多糖类物质及其修饰物或降解物，蛋白及其修饰物、改性物和降解的多肽类物质；
    所述天然多糖类物质包括透明质酸、羧甲基纤维素、甲基纤维素、羟乙基纤维素、羟丙基纤维素、海藻酸、葡聚糖、琼脂糖、肝素、硫酸软骨素、乙二醇壳聚糖、丙二醇壳聚糖、壳聚糖乳酸盐、羧甲基壳聚糖或壳聚糖季铵盐；
    所述蛋白包括各种亲水性或水溶性动植物蛋白、胶原蛋白、血清蛋白、丝素蛋白、弹性蛋白，所述蛋白降解物包括明胶或多肽；
    亲水或水溶性合成高聚物包括两臂或多臂聚乙二醇、聚乙烯亚胺、树枝体、合成多肽、聚氨基酸、聚丙烯酸、聚甲基丙烯酸、聚丙烯酰胺、聚甲基丙烯酰胺、聚乙烯醇、聚乙烯吡咯烷酮以及各种亲水性单体与亲水性单体、亲水性单体与疏水性单体的亲水或水溶性共聚物。
  16. 根据权利要求13所述高强度和韧性的光交联水凝胶材料，其特征在于，P 1’选自透明质酸、羧甲基纤维素、甲基纤维素、羟乙基纤维素、羟丙基纤维素、海藻酸、葡聚糖、琼脂糖、肝素、硫酸软骨素、乙二醇壳聚糖、丙二醇壳聚糖、壳聚糖乳酸盐、羧甲基壳聚糖、壳聚糖季铵盐。
  17. 根据权利要求13所述高强度和韧性的光交联水凝胶材料，其特征在于，所述式III双键官能团修饰的高分子衍生物，选自以下组分B-1～组分B-8中的结构：
    Figure PCTCN2020106113-appb-100020
    组分B-1～组分B-8中，m,n≥2。
  18. 根据权利要求12所述高强度和韧性的光交联水凝胶材料，其特征在于，所述光引发剂为光照下能够产生自由基的物质；
    所述光引发剂选自组分C-1、组分C-2、组分C-3、组分C-4、组分C-5或其衍生物；
    Figure PCTCN2020106113-appb-100021
  19. 如权利要求12所述高强度和韧性的光交联水凝胶材料的制备方法，其特征在于， 包括以下步骤：
    组分A，组分B和组分C溶于生物相容性介质得到水凝胶前体溶液；
    水凝胶前体溶液在光源照射下，发生光交联形成水凝胶。
  20. 根据权利要求19所述高强度和韧性的光交联水凝胶材料的制备方法，其特征在于，获得水凝胶前体溶液的方式可以采用以下两种方式：
    方式一：将组分A溶于生物相容性介质得到溶液A；将组分B溶于生物相容性介质得到溶液B；将组分C溶于生物相容性介质得到溶液C；将溶液A，溶液B和溶液C混合均匀得到水凝胶前体溶液；
    方式二：将组分A，组分B和组分C混合溶于生物相容性介质得到水凝胶前体溶液。
  21. 根据权利要求19所述高强度和韧性的光交联水凝胶材料的制备方法，其特征在于，所述生物相容性介质选自蒸馏水、生理盐水、缓冲液、脱细胞基质或细胞培养基溶液。
  22. 根据权利要求19所述高强度和韧性的光交联水凝胶材料的制备方法，其特征在于，混合均匀形成的水凝胶前体溶液中，组分A浓度为0.1％wt-60％wt，优选为1％wt-40％wt，组分B的浓度为0.01％wt-20％wt，优选为0.05％wt-10％wt，组分C的浓度为0.01％wt-5％wt，优选为0.1％wt-3％wt，高分子总浓度为0.1％wt-60％wt，优选为1％wt-10％wt。
  23. 根据权利要求19所述高强度和韧性的光交联水凝胶材料的制备方法，其特征在于，光源的波长为250-500nm，优选为300-450nm，进一步优选为365、375、385、395、405nm。
  24. 一种用于制备高强度和韧性的光交联水凝胶材料的试剂盒，其特征在于，所述试剂盒包含：组分A-如权利要求1-11中任一项所述的邻硝基苄基类光扳机修饰的光敏高分子衍生物；组分B-双键官能团修饰的高分子衍生物，组分C-光引发剂，及有关水凝胶制备及应用的说明书；
    所述双键官能团修饰的高分子衍生物，具有式III所示结构：
    Figure PCTCN2020106113-appb-100022
    式III中，R 1’，R 2’、R 3’独立地选自氢、卤原子、芳环、杂芳环、脂环、脂杂环、烷基或改性烷基；R 4’选自烷基、醚键类取代基、酯键类取代基、碳酸酯键类取代基、酰胺键类取代基、胺基甲酸酯键类取代基、巯基甲酸酯键类取代基或磷酸酯键类取代基；
    n≥2；
    P 1’为一种亲水或水溶性天然高聚物或合成高聚物，或P 1’独立的选自多种亲水或水溶性天然高聚物或合成高聚物；
    所述光引发剂为光照下能够产生自由基的物质；
    所述光引发剂选自组分C-1、组分C-2、组分C-3、组分C-4、组分C-5或其衍生物；
    Figure PCTCN2020106113-appb-100023
  25. 如权利要求12所述高强度和韧性的光交联水凝胶材料的应用，其特征在于，包括以下应用：
    所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-组织免缝合材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-组织修复材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-术后防黏连材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备术后创面封闭-口腔溃疡材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备组织液渗漏封堵-肠漏封堵材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备组织液渗漏封堵-脑脊液封堵材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备组织液渗漏封堵-胃漏封堵材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备止血材料-肝脏止血材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备止血材料-肾脏止血材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备止血材料-脾脏止血材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备止血材料-胰止血材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备止血材料-骨断面止血材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备止血材料-动脉止血材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备止血材料-心脏止血材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-补片固定材料的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-瓣膜固定材料的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-黏膜固定材料的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-组织固定材料的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备粘合材料-骨固定材料的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备组织加固材料-贴片材料的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备组织工程支架材料-软骨修复材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备组织工程支架材料-骨修复材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备组织工程支架材料-骨/软骨复合缺损修复材料或药物的应用；
    所述高强度和韧性的光交联水凝胶材料在3D打印(FDM)材料-生物墨水的应用；
    所述高强度和韧性的光交联水凝胶材料在3D打印(SLA)材料-生物墨水的应用；
    所述高强度和韧性的光交联水凝胶材料在3D打印(DLP)材料-生物墨水的应用；
    所述高强度和韧性的光交联水凝胶材料在3D打印-结合介入科手术的应用；
    所述高强度和韧性的光交联水凝胶材料作为制备细胞、蛋白、药物载体上的应用。
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