CN110171131A

CN110171131A - A kind of biomaterial for light-operated 3D printing

Info

Publication number: CN110171131A
Application number: CN201810700414.3A
Authority: CN
Inventors: 欧阳宏伟; 洪逸; 周飞飞; 章淑芳
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2018-06-29
Filing date: 2018-06-29
Publication date: 2019-08-27

Abstract

The present invention provides a kind of for light-operated 3D printing biomaterial, it can be used as the raw material of 3D printing, or a kind of basic material that can be processed by 3D printer, it is processed by way of similar printing, and a kind of tissue or organ with labyrinth is formed, it is used directly for various uses.It include the macromolecular of photoresponse crosslinked group modification, the macromolecular of adjacent nitro benzyl class light trigger modification, photoinitiator for light-operated 3D printing biomaterial.

Description

A kind of biomaterial for light-operated 3D printing

Technical field

The present invention relates to a kind of 3D printing system, the biomaterial for printing is also related to.

Background technique

It is well known that clinically needing a large amount of engineered tissues due to donor tissue and organ shortage.Although having attempted to Many methods come manufacturing engineering tissue, such as electrostatic spinning, squeeze out 3D printing and textile technology.But they can only all produce phase To simple three-dimensional structure, it is not able to satisfy the demand of clinical application.Therefore, there is an urgent need to manufacturing with high-resolution complicated and The tissue construct of layering is used for clinical use.Recently, the 3D printing technique based on digital light processing (DLP) be used to manufacture tool There are high print speed, minute yardstick resolution ratio, the complex three-dimensional micro-structure of thick vertical structure and strong Coating combination characteristic.It can be with mould Intend the precise geometrical body of natural tissues to create complicated 3D blood vessel tissue, this has stepped huge one in field of tissue engineering technology Step.

3D printing technique is actually the rapid molding device for the technologies such as utilize photocuring and paper layer folded.The design of 3D printing Process is: first passing through computer modeling software and establishes three-dimensional model, then the threedimensional model that will simply be referred to as is sliced, is divided into layer-by-layer cut Then face instructs printer successively to print.

Currently, being applied to medical domain, the method for printing living tissue has: the printing of DLP photocuring and extruded type printing. The liquid bath that resin can be accommodated in DLP photocuring printing device comprising one, can be by the ultraviolet lighting of specific wavelength for holding Rear cured resin is penetrated, DLP imaging system is placed in below liquid bath, and imaging surface is placed exactly in liquid bath bottom, passes through energy and figure (this layer of resin and the resulting cross-sectional shape of front cutting are complete for the pellicular resins of shape control, each curable certain thickness and shape It is exactly the same).The shift mechanism of one lifting pallet of setting above liquid bath, pallet stepping, to pallet (or molded layer) with The forming surface of a thickness is formed between liquid bath, after the completion of the exposure of each section upwards lifting certain altitude (this highly with layering Consistency of thickness) so that the solid resin of current curing completion separates with liquid bath bottom surface and is bonded in lifting plate or last molding Resin layer on, in this way, generating 3D solid by successively exposing and being promoted.DLP formula 3D printer, optical system are solid It is fixed, and optical system only completes the printing of a thickness every time.It is general by the way of first rising and dropping again, i.e., if with 0.1mm layers Thickness printing, first raises 5mm, then decline 4.9mm.Model is immersed in feed liquid each forming surface after liquid level, molding.But it is this Mode also can be problematic, and feed liquid surface tension will affect shape layer thickness and molding effect.Also, each forming surface is in liquid Face, therefore printing requires for liquid bath to be full of every time, even if the practical material quantity of entity to be formed is much smaller than the volume of liquid bath, Liquid bath must be full of, just can guarantee each forming surface in liquid level；Also, remaining feed liquid secondary can not use after shaping. In addition, DLP photocuring printing shift mechanism is also immersed in feed liquid, and in order to make each forming surface in liquid level, balance is needed to mention Difference in volume caused by drawing mechanism sinks, therefore there is provision of balance weight in liquid bath, shift mechanism, balance weight and pallet are respectively positioned on liquid In slot, shift mechanism, balance weight occupy the sectional area of liquid bath, and effective shaping area (tray area) is caused to be less than the section of liquid bath Product, effective shaping area are small.

Existing extrusion and artificial soft tissue's preparation method of photocuring composite molding, comprising the following steps: 1, to artificial Modeling of Soft Tissue obtains artificial soft tissue's model；2, each layer in artificial soft tissue's model of profile is handled: is beaten with 3D Print delamination software calculates each layer in artificial soft tissue's model of profile information, and the profile information is generated and squeezes out spray head Operating path；3, it prepares photocuring composite solution: first making active somatic cell, growth factor and collagen solution three mixing to be mixed Liquid, then the injection light cured hydrogel into mixed liquor are closed, visible light photo initiators is then added, obtains being able to maintain a setting The hydrogel composites of shape；4, the photocuring composite solution prepared using step 3 is carried out soft group artificial as raw material using 3D printer It weaves standby: 4-1 and controls hydraulic extruder head by operating path in squeezing out hydrogel composites on workbench, form half solidification shape Colloid layer；4-2, photocuring is carried out to colloid layer, obtains cured layer.Hydraulic extruder head is fixedly connected with photocuring head, works as liquid When extrusion lifts one's head in running order, photocuring head is closed；It is hydraulic when motion profile when hydraulic extruder head presses work resets Extruder head is closed, and photocuring head is in running order.

The shortcomings that molding mode of this biological tissue is: 1, either DLP mode or extruded type can not all make It is cooperated with multiple material and completes the molding task of a biological tissue, therefore cannot achieve the hybrid process of multiple material.And Active organisms are the non-uniform mixing systems comprising various structures, many kinds of substance ingredient, and above-mentioned method is unable to complete realization The molding of non-uniform mixing system.2, the charging of DLP, shaping speed are fast, but the feed liquid wasted is more, the first use rate of feed liquid It is low.This is also required to improve design to existing traditional prints, it is desirable to can print the bioactive materials of increasingly complex structure.

So far, many materials include natural polymer: collagen, silk fiber, gelatin, alginate and synthesized polymer Object: polyethylene glycol (PEG) be used to squeeze out 3D printing, these materials as biological 3D printing, also referred to as " bio-ink ".So And some of them show poor mechanical performance or slower gel time, limit it in the 3D printing based on DLP Using.

Meanwhile in order to solve this problem it is necessary to have the mixing water-settings of adjustable mechanical performance and quick-gelatinizing Matrix biological hydrogel.This just needs to provide some improved bio-inks, is applicable in and prints complicated biomaterial, meets real The needs on border.

Summary of the invention

On the one hand, one of the objects of the present invention is to provide one kind can be realized more material alternatingly feeds, realizes non-homogeneous The 3D printing system of mixed system.

A kind of 3D printing system, including optical system, feeding machanism, hoistable platform and chamber；Hoistable platform and chamber formation are held The space of feeding machanism supplied materials is connect, hoistable platform and feeding machanism are independent；Printing every time, hoistable platform opposing optical system step Into.

Hoistable platform one thickness of each stepping, the purpose of hoistable platform stepping are to enable optical system to be formed Strata it is burnt, realize photocuring.Feeding machanism is except optical system, and the feed liquid of feeding machanism is in the photocuring area of optical system Except domain, in printing, without shifting feed liquid, photocuring can be carried out.Hoistable platform independently refers to rising with feeding machanism Drop platform is not merged with feeding machanism, but mechanism independent, and the injection hoistable platform that feeding machanism quantifies feed liquid rises The lifting of drop platform not will lead to the feed of feeding machanism.

Optical system

Optical system uses the optical imaging system of DLP technology, the exposure area of optical system and every layer of wheel to be formed It is wide identical.Real time imagery exposure can be carried out according to the sectional view of different shape layers, exposure area is radiated in liquid material, liquid Expect curing molding, non-irradiated area, liquid material is still liquid.

Hoistable platform

In some preferred modes, hoistable platform be can independent-lifting platform, hoistable platform accepts feeding machanism Feed after hoistable platform stepping, can issue the signal for needing to be fed to feeding machanism, but the stepping of hoistable platform is not direct Feed liquid is caused to flow into platform.For hoistable platform in the photocuring region of optical system, the feed liquid in hoistable platform receives optical system Stereolithography is completed in the illumination of system.

In some preferred schemes, optical system is on hoistable platform.Printing, hoistable platform are stepped down by every time. Preferably, hoistable platform includes piston, and piston is located at intracavitary, and piston accepts feed, and piston is driven by platform actuator step-by-step movement.

Preferably, platform actuator is located under piston.Preferably, the upper surface of piston is contacted with feed liquid.Some excellent In the scheme of choosing, the bottom of platform actuator and piston is fixed, and platform actuator includes driving motor, screw body and sliding block, Screw rod is connect with driving motor, and nut is fixed with sliding block, and sliding block is connect with piston.Screw body converts the torque of driving motor Be in line movement, and sliding block is used as guide part when piston motion with piston stepping downward or upward, chamber simultaneously.Platform actuator It is not take up contact area and the space of piston and feed liquid, all areas of the upper surface of piston are that can be used for Stereolithography Effective area.

Chamber

In some preferred modes, for accommodating feed liquid or bio-ink or biomaterial, hoistable platform exists chamber Intracavitary lifting.It prints each time, feed liquid addition is intracavitary, and when intracavitary feed liquid liquid level, which reaches thickness, to be required, optical system is carried out Photocuring.

In some preferred schemes, print system includes bracket, and chamber is fixed on bracket.Preferably, chamber is by being set to block Through-hole on shape ontology is formed, and block-shaped body is fixed on bracket.Preferably, the section of chamber be rectangle, perhaps square or The conventional shapes such as circle or ellipse.Preferably, block-shaped body is equipped with the channel for accommodating platform actuator or slot.Platform drives The upward-downward translation displacement that the sliding block of moving part can not be interfered in the channel of block-shaped body or slot.Preferably, block-shaped body is The conventional shapes such as rectangular slab or square plate, or round or ellipse.

Feed

Feeding machanism feeds to hoistable platform, and feed quantity is substantially equal to form the required reduction of feed volume of current layer every time. It is so-called of substantially equal, refer to that the amount of feed can satisfy the required reduction of feed volume of molding, and make liquid level and thickness effective Solidification range is not absolute equal in mathematical meaning.

In some preferred schemes, feeding machanism has feed unit, and feed unit has a respective barrel, feeding rod, Discharge tip and quantitative driving mechanism, feeding rod are connect with quantitative driving mechanism.Feeding rod pushes the feed liquid in barrel from discharging Nozzle squeezes out, and feed liquid is added dropwise in hoistable platform discharge tip.

Preferably, the quantity of feed unit is 1 or the quantity of feed unit is multiple.It is multiple to refer to for material list Number >=2 of member.

Feed mode is controlled by controller, and controller controls the feeding of quantitative driving mechanism.Preferably, some confession is specified Material unit feed, alternatively, multiple feed units alternately realize feed-Light Curing.For example, having the first feed unit and second Two units of feed unit, the first feed unit feed, photocuring, hoistable platform stepping is primary, the second feed unit feed, light Solidification；Hoistable platform stepping is primary, then the first feed unit feed, photocuring ... ..., in this way, multiple feed units alternately into Row feed-photocuring.In this case, reduction of feed volume needed for a feed quantity of each feed unit meets current formable layer.

Preferably, alternatingly feed is that multiple-unit is fed in order or different feed units intersects feed.It supplies in order The case where material, than if any the first feed unit, the second feed unit and third feed unit, by first, second, third sequence Successively feed-photocuring.Different units intersects feed, such as the first feed unit, and the second feed unit and third are for material list Member, the first feed unit feed-photocuring, the second feed unit feed-photocuring, then the first feed unit feed-light is solid Change, third feed unit feed-photocuring is completed as long as front and back is fed twice by different units.

Alternatively, multiple feed units are fed simultaneously, it is fed after the completion photocuring again.For example, having the first feed unit and Two units of feed unit two, the first feed unit and the second feed unit are fed simultaneously, and the feed quantity summation of all units is full Reduction of feed volume needed for the current formable layer of foot, feed carry out photocuring again after the completion.The feed liquid dropwise addition position of two units is the same, It can be different with position.

Alternatively, some or multiple feed units are formerly fed, other one or more feed units are in first feed knot Shu Houzai is fed, after all feed units complete feed, then photocuring.For example, having the first feed unit and the second feed Two units of unit, the first feed unit are first fed, and the second feed unit is supplied again after the first feed unit completes feed Material, reduction of feed volume needed for the feed quantity summation of all units meets current formable layer, feed carry out photocuring again after the completion.After supply It, can also be different with position position can be added dropwise with the feed liquid for the unit being first fed in the unit of material.

Alternatively, some or several formative stages are using specified feed unit feed, some or several formative stages are adopted It is fed simultaneously with multiple-unit, some or several formative stages use multiple-unit alternatingly feed.

Alternatively, some feed unit is specified to be fed, other unit break-ofves.In this way, forming the printing of homogenous material.

Quantitative driving mechanism

Quantitative driving mechanism is for quantitatively pushing feeding rod, the control to quantitative driving mechanism, realizes to feed mode Control.In some preferred schemes, quantitative driving mechanism includes feeding actuator, and feeding actuator is connect with feeding rod.It is excellent Choosing, feeding actuator includes fixture, the connection that feeding rod is clamped in fixture, realizes feeding actuator and feeding rod.Fixture pine When opening feeding rod, feeding rod is detached from feeding actuator.Feeding actuator uses motor and transmission mechanism (such as screw body), electronic Push rod, cylinder etc..

Preferably, each barrel has respective barrel frame, and barrel is fixed on barrel frame.Preferably, barrel frame includes fixing Portion and movable part, movable part are connect with barrel, there is locking member between movable part and fixed part.The relatively fixed position of movable part is moved Afterwards, the mounting height of barrel is promoted.Preferably, the short transverse of movable part is equipped with multistage screw hole, and fixed part is equipped with screw hole, locking Part is screw or bolt and nut.The corresponding mounting height of every level-one screw hole.Preferably, the short transverse of fixed part is equipped with multistage Screw hole.To increase the mounting height adjusting range of barrel.The distance between two-stage screw hole of fixed part can be with movable part The distance between two-stage screw hole difference, thus variant differential adjustment.

Position adjusting mechanism

Position adjusting mechanism is used to adjust the position of feeding machanism, realizes that feed liquid is added dropwise in hoistable platform feeding machanism Designated position.In some preferred schemes, 3D printer includes position adjusting mechanism, and feeding machanism is installed on position adjustment machine Structure.Each feed unit has independent position adjusting mechanism.Alternatively, all feed units are installed on the same position adjustment machine Structure.Alternatively, certain several feed unit is installed on the same position adjusting mechanism, remaining feed unit is installed on other position tune Complete machine structure.

Preferably, position adjusting mechanism includes pedestal and positioning actuator and positioning sliding block positioned at pedestal, sliding block of transposing In slope, slope is low close to one end of hoistable platform, the other end is high.The presence on slope makes the feed liquid of barrel bear certain gravity Effect avoids feed liquid from remaining in nozzle, and reduction of feed volume is accurate when keeping being fed.Preferably, positioning sliding block and positioning guide rail cooperation, Pedestal is equipped with positioning limit switch.Limit switch of transposing limits the displacement section of positioning sliding block.Transpose actuator using motor, Cylinder, electric pushrod etc..

Preferably, barrel frame is fixed on positioning sliding block.The mounting height for adjusting barrel makes the axis of barrel and quantitative driving The thrust direction of mechanism is conllinear.

Drain

In more file printing tasks, it is sometimes desirable to first the first feed liquid be drained, add second of feed liquid.Some In preferred scheme, print system has drainage mechanism.Preferably, it is preferred that piston and cavity gap cooperate, between piston and chamber Gap as sump pit.When feed, the amount of feed liquid is larger, the gap location of piston and chamber due to feed liquid surface tension effects, Feed liquid will not drain from gap.After a photocuring, the amount of feed liquid becomes seldom, and uncured liquid can be arranged from sump pit It walks.

Alternatively, piston and chamber sealing cooperate, drainage mechanism is pipette.When needing drain, pipette protrudes into non-forming area Domain siphons away remaining liq.Preferably, pipette is installed on imbibition driving mechanism, and the reciprocating motion of imbibition driving mechanism makes pipette Into intracavitary or withdraw from intracavitary.Preferably, pipette is connect with negative pressure device.Remaining feed liquid is siphoned away by negative pressure.

After former feed liquid is drained, another feed liquid is added, both front and back feed liquid is avoided to influence each other, interfere.

On the other hand, the present invention provides a kind of 3D printing method, this method comprises:

1), prepare 3D printing system and feed liquid, input print out task, feed liquid is packed into the barrel for undertaking feed task, Barrel installation is in place；

2), hoistable platform is in one thickness of intracavitary decline；

3), the space that barrel is surrounded to intracavitary feed, feed liquid full of hoistable platform and chamber；

4), optical system completes the solidification of current layer feed liquid to feed liquid photocuring.

In some schemes, when print out task only uses a kind of material and printed, after step 3), step is repeated 2) -4), until completing print out task.Feeding machanism provides the reduction of feed volume for meeting one layer of printing every time, makes feed liquid layer always in light Within the scope of the photocuring of system.After the completion of not drain or previous thickness solidify between upper and lower two thickness, remaining feed liquid When draining, but being fed next time, reduction of feed volume is able to satisfy feed liquid layer in the focusing range of optical system.Current printable layer needs more For how many material, the feed liquid that do not confess is stored in barrel few feed liquid, still can be practical for other print out task, improves primary charging Utilization rate.

Also, when occurring hanging oneself from a beam between upper layer and lower layer or when cantilever design, feed liquid is completed to be full of a preceding printable layer, feed liquid The buoyancy cured overarm of support current layer or cantilever, avoid overarm or cantilever from collapsing, no overarm (or cantilever) can be molded The engraved structure collapse, deformed, engraved structure increase the bond area of active material (such as cell).

In some schemes, after step 4), 5A is entered step), judge whether current layer needs using another feed liquid Print out task is completed, if it is not, hoistable platform declines a thickness, prepares the printing of later layer；If so, drain, keeping lifting flat Platform is maintained at current layer position.In some schemes, when current layer needs another feed liquid to complete the printing of other structures, drain After being located at correct position with hoistable platform, the feeding machanism equipped with specified material is fed to hoistable platform, after the completion of feed flow, optics System repeats step 5A to feed liquid photocuring), until current layer is completed.

When carrying out current layer, 5A is entered step).

In some schemes, after step 4), 5B is entered step), judge whether later layer and current layer use same material Material, if it is not, then repeating step 2) -5)；If so, drain, hoistable platform is made to be maintained at current layer position, equipped with specified material Feeding machanism is fed to hoistable platform, and after the completion of feed flow, optical system is to feed liquid photocuring.

After the completion of current layer print out task, 5B is entered step).

Preferably, the method for making hoistable platform be maintained at current location includes: to have printed one layer, and hoistable platform does not decline； Alternatively, having printed one layer, hoistable platform one thickness of decline；Hoistable platform is set to reset a thickness upwards again.First drain makes again Hoistable platform keeps current layer position, so that hoistable platform is kept current layer position, again drain or protects hoistable platform It holds current layer position and drain while carrying out, be ok.

On the other hand, another object of the present invention provides a kind of biomaterial or bio-ink, can be used as 3D and beats The raw material of print, or a kind of basic material that can be processed by 3D printer are processed by way of similar printing, And a kind of tissue or organ with labyrinth is formed, it is used directly for various uses.

It is an object of the present invention to provide a kind of light-operated 3D printing bio-ink and its applications, improve existing 3D printing bio-ink Mechanical performance is poor and the slow problem of gelation time.

The technical solution adopted by the present invention is that:

The present invention provides a kind of light-operated 3D printing bio-ink, and the glue is divided greatly by what photoresponse crosslinked group was modified Son, the macromolecular of adjacent nitro benzyl class light trigger modification, photoinitiator and deionized water composition；The photoresponse crosslinked group is repaired The macromolecular quality final concentration of macromolecular and adjacent nitro benzyl class light the trigger modification of decorations with deionized water meter be 0.1~ 10%, the photoinitiator quality final concentration is calculated as 0.001~1% with deionized water amount；The photoresponse crosslinked group is repaired The grafting Replacement rate of photoresponse crosslinked group is 10~90% in the macromolecular of decorations, and photoresponse crosslinked group is methacryl Amine, methacrylic anhydride, glycidyl methacrylate or acryloyl chloride；The adjacent nitro benzyl class light trigger is modified big The grafting Replacement rate of adjacent nitro benzyl class light trigger is 1~100% in molecule.

Further, shown in the macromolecular such as formula (I) of the adjacent nitro benzyl class light trigger modification, in formula (I), R₁For-H Or it is selected from-CO (CH₂)xCH₃、-CO(CH₂CH₂O)_xCH₃、-CO(CH₂)_x(CH₂CH₂O)_yCH₃Ester bond class, selected from-(CH₂)_xCH₃、-(CH₂CH₂O)_xCH₃、-(CH₂)_x(CH₂CH₂O)_yCH₃、Ehter bond class, be selected from-COO (CH₂)_xCH₃、-COO (CH₂CH₂O)_xCH₃、 -COO(CH₂)_x(CH₂CH₂O)_yCH₃Carbonic acid ester bond class, be selected from-CONH (CH₂)_xCH₃、 -CONH (CH₂CH₂O)_xCH₃、-CONH(CH₂)_x(CH₂CH₂O)_yCH₃Isocyanic acid ester bond class, wherein x and y >=0 and be integer；R₂For-H Or it is selected from-O (CH₂)_xCH₃、-O(CH₂CH₂O)_xCH₃、 -O(CH₂)_x(CH₂CH₂O)_yCH₃Substituent group, wherein x and y >=0 and be Integer；R₃Selected from amino connecting key-O (CH₂)_xCONH(CH₂)_yNH-, halogenated class connecting key-O (CH₂)_xIt is connected with carboxyl class Key-O (CH₂)_xCO-, wherein x and y >=1 and be integer；R₄For-H or-CONH (CH₂)_xCH₃, wherein x >=0 and be integer；P₁ For macromolecular；

Further, the preferably described adjacent nitro benzyl class light trigger is adjacent nitro benzyl.

Further, the macromolecular of the macromolecular of the photoresponse crosslinked group modification and the modification of adjacent nitro benzyl class light trigger In natural biological macromolecular be glucan, hyaluronic acid, gelatin, sodium alginate, chondroitin sulfate, fibroin, chitosan, carboxylic Methylcellulose or collagen, one of polyethylene glycol or lemon acid polymer (PEGMC).

Further, the photoinitiator is 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone (2-Hydroxy- 4'- (2-hydroxyethoxy) -2-methylpropiophenone, I2959) or phenyl (2,4,6- trimethylbenzoyls One of base) phosphoric acid lithium salts (lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP)；Institute The mass ratio of the macromolecular of the photoinitiator and the graft modification of photoresponse crosslinked group stated is 1~3:100.

Further, the grafting Replacement rate of the macromolecular of the photoresponse crosslinked group modification is 10~30%；Neighbour's nitre The grafting Replacement rate of the macromolecular of base benzyl class light trigger modification is 1~20%.

Further, the macromolecular of the photoresponse crosslinked group modification is to be grafted the methacrylic anhydride that Replacement rate is 10% The methyl-prop that the amine-modified gelatin of the methacryl that gelatin, the grafting Replacement rate of modification are 90%, grafting Replacement rate are 40% The amine-modified gelatin of the methacryl that gelatin, the grafting Replacement rate of olefin(e) acid acid anhydride modification are 20%, grafting Replacement rate are 30% The chondroitin sulfate or grafting that the methacrylic anhydride that collagen, the grafting Replacement rate of methacrylic anhydride modification are 90% is modified take For the rate carboxymethyl cellulose amine-modified for 10% methacryl, the acryloyl chloride that grafting Replacement rate is 10% is modified poly- Ethylene glycol, one of the glucan that the glycidyl methacrylate that grafting Replacement rate is 20% is modified.

Further, the macromolecular of the adjacent nitro benzyl class light trigger modification is to be grafted the adjacent nitro that Replacement rate is 100% The hyaluronic acid of benzyl modification, the sodium alginate for being grafted the adjacent nitro benzyl modification that Replacement rate is 50%, grafting Replacement rate are The gelatin for the adjacent nitro benzyl modification that chondroitin sulfate, the grafting Replacement rate of 10% adjacent nitro benzyl modification are 30%, grafting The collagen for the adjacent nitro benzyl modification that fibroin, the grafting Replacement rate of adjacent nitro benzyl that Replacement rate is 90% modification are 100% or It is grafted the chitosan that the adjacent nitro benzyl that Replacement rate is 10% is modified, the lemon acid polymer of 10% adjacent nitro benzyl modification One of (PEGMC).

Further, the macromolecular quality final concentration of the photoresponse crosslinked group modification is 3- with deionized water meter 10%, the macromolecular quality final concentration of adjacent nitro benzyl class light trigger modification is calculated as 2-4%, the light with deionized water amount Initiator quality final concentration is calculated as 0.03-0.2% with deionized water amount.

The present invention also provides a kind of application of light-operated 3D printing ink in skin injury reparation.

The present invention also provides a kind of application of light-operated 3D printing ink in Articular cartilage repair.

Further, the application are as follows: the light-operated 3D printing ink is utilized into the 3D based on digital light processing (DLP) Printing technique is printed as bracket and is implanted into the position of defect of skin, realizes skin histology reparation.

The present invention generates aldehyde radical after illumination excitation using adjacent nitro benzyl class light trigger, and the aldehyde radical and amino of generation can Reaction forms the principle of powerful chemical key, meanwhile, the macromolecular of photoresponse crosslinked group modification solidifies rapidly under light illumination, double cross Network of networking enhances mechanical property, and it is a kind of ideal that the porous precise and tiny structure of 3D printing, which can achieve the purpose that quick repair deficiency, The light-operated 3D printing ink for defect of skin or osteochondral defect reparation.

Advantages of the present invention is for newly-designed printer:

1, the region charging that feeding machanism is surrounded in a manner of being added dropwise to hoistable platform and chamber, feeding machanism and hoistable platform For mutually independent mechanism, it is not necessarily to pre-feed；The feed liquid added every time and feed liquid needed for each formable layer are flux matched, improve one The waste of feed liquid can be greatly reduced in the utilization rate of secondary charging.

2, each feeding thickness is thick from level to level, and when printing engraved structure, uncured region still keeps liquid, then after When one layer of printing, the material of liquid can support virgin material, so that later layer material be avoided to collapse, be precisely accomplished printing form.

3, by the control to feed unit, it is non-that the layer-by-layer printing alternate of multiple material, multiple material same layer be can be realized A variety of charging printing models such as even mixing printing, homogenous material printing, printing model is flexible and changeable, can be realized the non-equal of material Even mixed system molding, the more true practical biosystem of simulation.

4, the position of feeding machanism can be squeezed out by adjusting, the position that control feed liquid instills, more really simulation is real Border biosystem.

5, the area of liquid level and hoistable platform are of substantially equal, and effective photocuring area is big.

In addition, compared with prior art, the present invention is mainly reflected in for new biomaterial:

The mechanical property of light-operated 3D printing ink of the invention, can be controlled by lighting activation.It is raw before illumination excitation Aldehyde radical is free of in object glue, can not react to form double-layer network with amino, therefore mechanical property is poor.After lighting activation, Aldehyde radical is generated on adjacent nitro benzyl class tabula rasa machine molecule, can quickly react with amino light-operated 3D printing ink, to make Biological glue has preferable mechanical property.It, can be with by increasing the concentration of the macromolecular of adjacent nitro benzyl class light trigger modification Increase mechanical property.This law invention is modified using the macromolecular and adjacent nitro benzyl class light trigger of photoresponse crosslinked group modification Macromolecular, biological safety is good, and usage simply can be used for Repair of tissue defect regenerative medicine field, realizes tissue perfection reparation.

Detailed description of the invention

Fig. 1 is the illustraton of model (upper layer bracket) of present invention cartilage printing processed.

Fig. 2 is the overall structure figure of printer of the invention.

Fig. 3 is the structure chart of platform actuator and hoistable platform.

Fig. 4 is the structure chart of hoistable platform bracket.

Fig. 5 is the schematic diagram that feeding machanism 2 feeds to hoistable platform 3.

Fig. 6 is the feed unit structure chart with liftable barrel frame.

Fig. 7 is the feed unit structure chart with fixed height barrel frame.

Fig. 8 is the structure chart of position adjusting mechanism.

Fig. 9 is the structure chart of hoistable platform piston.

Figure 10 is using a kind of file printing solid corium engraved structure schematic diagram.

Figure 11 is the grid layer and the molding stereoscopic schematic diagram of column array layer same material of Figure 10.

Figure 12 is the grid layer and two kinds of molding stereoscopic schematic diagrams of different materials of column array layer of Fig. 1.

Figure 13 is to use the molding schematic diagram of another material using a kind of molding of material, remainder layer for continuous N layers in Figure 10.

Figure 14 is the pictorial diagram for the printing corium that the present invention is established model by Figure 10.

The vertical view micro-structure diagram of corium shown in Figure 15 A Figure 14, Figure 15 B are the sectional drawings of corium shown in Figure 14.

Figure 16 A-16C is that the dermal scaffold printed using bio-ink of the invention is copolymerized burnt microstructure characterizations figure (suspension beam structure, 3 axis intercommunicating pores of micron order high-precision).

Figure 17 A-17C is that the dermal scaffold printed using bio-ink of the invention is copolymerized burnt microstructure characterizations figure Wherein, living cells frees organ cell's activity characterization and is copolymerized burnt photo, and volume is 1 cubic millimeter, and cell Proliferation is unaffected, and 7 95%) its activity is greater than.

Figure 18 is the cartilage illustraton of model in a specific embodiment of the invention.

Figure 19 is the vertical view micro-structure diagram in the different holes printed.

Figure 20 is the pictorial diagram in the different holes printed.

It is described with reference to the accompanying drawings

As shown in Fig. 2, a kind of 3D printing system, including optical system 1, feeding machanism 2, hoistable platform 3 and chamber 302；It rises It drops platform 3 and chamber 302 forms the region for accepting 2 supplied materials of feeding machanism, hoistable platform 3 and feeding machanism 2 are independent；Printing every time, 3 opposing optical system stepping of hoistable platform.Fig. 1 is the skin histology for the hollow out state that 3D printing system is produced.

Optical system

Hoistable platform

Hoistable platform be can independent-lifting platform, hoistable platform accept feeding machanism feed, after hoistable platform stepping, The signal for needing to be fed can be issued to feeding machanism, but the stepping of hoistable platform does not directly result in feed liquid and flows into platform.It rises Platform drops in the photocuring region of optical system, and the feed liquid in hoistable platform receives the illumination of optical system, completes photocuring Molding.

As shown in Fig. 2, optical system 1 is on hoistable platform 3 in some preferred schemes.Printing every time, lifting are flat Platform 3 is stepped down by.Hoistable platform 3 includes piston 301, and piston 301 is located in chamber 302, and piston 301, which is accepted, to be fed, piston 301 by The driving of 5 step-by-step movement of platform actuator.

As shown in figure 9, sealing ring 303 is arranged on piston 301 when piston 301 and chamber 302 are tightly connected.

Preferably, platform actuator is located under piston.Preferably, the upper surface of piston is contacted with feed liquid.Such as Fig. 3 institute Show, in some preferred schemes, platform actuator 5 and the bottom of piston 301 are fixed, and platform actuator 5 includes driving motor 501, screw body 502 and sliding block 503, screw body 502 are connect with driving motor 501, and nut is fixed with sliding block, sliding block 503 It is connect with piston 301.The torque of driving motor 501 is converted into moving linearly by screw body 502, and sliding block 503 is with piston 301 Stepping downward or upward, guide part when chamber 302 is moved as piston 301 simultaneously.Platform actuator is not take up piston and feed liquid Contact area and space, all areas of the upper surface of piston be the effective area that can be used for Stereolithography.

Chamber

Chamber is for accommodating feed liquid, and hoistable platform is in intracavitary lifting.It prints each time, feed liquid addition is intracavitary, when intracavitary material When liquid liquid level reaches thickness requirement, optical system carries out photocuring.

As shown in figure 4, print system includes bracket 4 in some preferred schemes, chamber 302 is fixed on bracket 4.Chamber It is formed by the through-hole being set on block-shaped body, block-shaped body is fixed on bracket.The section of chamber is rectangle, or square, or The conventional shapes such as person's circle or ellipse.Block-shaped body is equipped with the channel for accommodating platform actuator or slot.Platform actuator The upward-downward translation displacement that sliding block can not be interfered in the channel of block-shaped body or slot.Block-shaped body is rectangular slab or rectangular The conventional shapes such as plate, or round or ellipse.

Feed

As shown in figure 5, feeding machanism 2 feeds to hoistable platform 3, and feed quantity is substantially equal to form the institute of current layer every time The reduction of feed volume needed.It is so-called of substantially equal, refer to that the amount of feed can satisfy the required reduction of feed volume of molding, and having liquid level The solidification range of effect, may slightly have surplus, not be absolute equal in mathematical meaning.

As shown in Figure 6 and Figure 7, in some embodiments, feeding machanism 2 has feed unit 6, and feed unit 6 has respectively Barrel 601, feeding rod 602, discharge tip 603 and quantitative driving mechanism 604, feeding rod 602 and quantitative driving mechanism 604 connect It connects.Feeding rod 602 pushes the feed liquid in barrel 601 and squeezes out from discharge tip 603, and feed liquid is added dropwise in lifting discharge tip 603 Platform.

The quantity of feed unit is 1 or the quantity of feed unit is multiple.Multiple numbers for referring to feed unit ≥2。

In some embodiments, alternatingly feed is that multiple-unit is fed in order or different feed units intersects feed. The case where being fed in order, than if any the first feed unit, the second feed unit and third feed unit, by first, second, Three sequence successively feed-photocuring.Different unit intersects feed, such as the first feed unit, the second feed unit and the Three feed units, the first feed unit feed-photocuring, the second feed unit feed-photocuring, then the first feed unit supplies Material-photocuring, third feed unit feed-photocuring, is completed as long as front and back is fed twice by different units.

Alternatively, in some embodiments, multiple feed units are fed simultaneously, it is fed after the completion photocuring again.For example, having Two units of one feed unit and the second feed unit, the first feed unit and the second feed unit are fed simultaneously, all units Feed quantity summation meet current formable layer needed for reduction of feed volume, carry out photocuring again after the completion of feed.The feed liquid of two units It is the same that position is added dropwise, it can also be different with position.

Alternatively, in some embodiments, some or multiple feed units are formerly fed, other one or more are for material list Member is fed again after first feed, after all feed units complete feed, then photocuring.For example, there is the first feed Two units of unit and the second feed unit, the first feed unit are first fed, and the second feed unit is completed in the first feed unit It is fed again after feed, reduction of feed volume needed for the feed quantity summation of all units meets current formable layer, after the completion of feed again Carry out photocuring.It, can also be different with position position can be added dropwise with the feed liquid for the unit being first fed in the unit being fed afterwards.

Alternatively, in some embodiments, some or several formative stages using specified feed unit feed, some or Several formative stages are fed simultaneously using multiple-unit, some or several formative stages use multiple-unit alternatingly feed.

Alternatively, in some embodiments, specifying some feed unit to be fed, other unit break-ofves.In this way, being formed The printing of homogenous material.

Quantitative driving mechanism

As shown in Figure 6 and Figure 7, quantitative driving mechanism 604 is for quantitatively pushing feeding rod 602, to quantitative driving mechanism The control to feed mode is realized in control.In some embodiments, quantitative driving mechanism includes feeding actuator 605, and feeding is driven Moving part 605 is connect with feeding rod 602.Preferably, feeding actuator 605 includes fixture 606, and feeding rod 602 is clamped in fixture 606, the connection of feeding actuator 605 and feeding rod 602 is realized.When fixture 606 unclamps feeding rod 602, the disengaging of feeding rod 602 is sent Expect actuator 605.Feeding actuator uses motor and transmission mechanism (such as screw body), electric pushrod, cylinder etc..Each barrel There is respective barrel frame, barrel is fixed on barrel frame.

As shown in fig. 7, in some embodiments, barrel frame 607 includes fixed part 608 and movable part 609, movable part 609 It is connect with barrel 601, there is locking member 610 between movable part 609 and fixed part 608.The relatively fixed portion 608 of movable part 609 is displaced Afterwards, the mounting height of barrel 601 is promoted.Preferably, the short transverse of movable part is equipped with multistage screw hole, and fixed part is equipped with screw hole, Locking member is screw or bolt and nut.The corresponding mounting height of every level-one screw hole.Preferably, the short transverse of fixed part is equipped with Multistage screw hole.To increase the mounting height adjusting range of barrel.The distance between two-stage screw hole of fixed part can be with activity The distance between the two-stage screw hole in portion difference, thus variant differential adjustment.

Position adjusting mechanism

Position adjusting mechanism is used to adjust the position of feeding machanism, realizes that feed liquid is added dropwise in hoistable platform feeding machanism Designated position.As shown in Fig. 2, in some embodiments, 3D printer includes position adjusting mechanism 7, feeding machanism 2 is installed on position Set adjustment mechanism 7.Each feed unit has independent position adjusting mechanism.Alternatively, all feed units be installed on it is same Position adjusting mechanism.Alternatively, certain several feed unit is installed on the same position adjusting mechanism, remaining feed unit is installed on separately Outer position adjusting mechanism.

As shown in figure 8, position adjusting mechanism includes pedestal 701 and positioning actuator 702 and positioning sliding block positioned at pedestal 703, positioning sliding block 703 is in slope, and slope is low close to one end of hoistable platform 3, the other end is high.The presence on slope makes the material of barrel Liquid bears certain gravity, and feed liquid is avoided to remain in nozzle, keeps the fine adjustment sliding block of reduction of feed volume when feed and transposes Guide rail cooperation, pedestal are equipped with positioning limit switch.Limit switch of transposing limits the displacement section of positioning sliding block.Positioning actuator Use motor, cylinder, electric pushrod etc..

Barrel frame is fixed on positioning sliding block.The mounting height for adjusting barrel makes the axis of barrel and quantitative driving mechanism Thrust direction is conllinear.

Drain

In more file printing tasks, it is sometimes desirable to first the first feed liquid be drained, add second of feed liquid.Front and back two Kind feed liquid can be same feed liquid, be also possible to different feed liquids.

In some embodiments, print system has drainage mechanism.Preferably, as shown in figures 4 and 9, piston 301 and chamber 302 clearance fits, the gap between piston 301 and chamber 302 is as sump pit.When feed, the amount of feed liquid is larger, piston and chamber Due to the surface tension effects of feed liquid, feed liquid will not drain gap location from gap.After a photocuring, the amount of feed liquid becomes very Few, uncured liquid can drain from sump pit.

Alternatively, in some embodiments, piston and chamber sealing cooperate, and drainage mechanism is pipette.When needing drain, imbibition Pipe protrudes into non-forming region and siphons away remaining liq.Preferably, pipette is installed on imbibition driving mechanism, and imbibition driving mechanism is past Multiple movement makes pipette enter intracavitary or withdraw from intracavitary.Preferably, pipette is connect with negative pressure device.It will be remaining by negative pressure Feed liquid siphons away.

1), prepare 3D printing system and feed liquid；

2), hoistable platform is in one thickness of intracavitary decline；

Feeding machanism provides the reduction of feed volume for meeting one layer of printing every time, makes feed liquid layer always in the photocuring model of optical system In enclosing.After the completion of not drain or previous thickness solidify between upper and lower two thickness, remaining feed liquid is drained, but is supplied next time When material, reduction of feed volume is able to satisfy feed liquid layer in the focusing range of optical system.Current printable layer needs how many feed liquids to expect for how many, The feed liquid that do not confess is stored in barrel, still can be practical for other print out task, improves the utilization rate once to feed.

In some embodiments, when print out task only uses a kind of material and printed, after step 3), step is repeated 2) -4), until completing print out task.Print out task includes being fed with which barrel, the sequence of feed, the supply of feed liquid And position and the photocuring profile of optical system etc..

For printing three-dimensional engraved structure as shown in Figure 1, which is in by grid layer and column array Interval composition.When the non-homogenous material of the engraved structure, printed material is packed into barrel, barrel is with liquid to intracavitary feed.Just When the beginning, hoistable platform is flushed with the top surface of chamber.

Start to print, hoistable platform declines a thickness, and barrel feed, irradiation optical system feed liquid liquid level, feed liquid is by light According to figure curing molding mold the D1 layer of the alternate grille-like of skeleton and hole such as Figure 10 and 11；One layer of printing is completed. Hoistable platform declines a thickness, and barrel is fed again, liquid level is made to rise to chamber top；Irradiation optical system feed liquid liquid level, feed liquid The D2 layer of column array is molded such as Figure 10 and 11 by the figure curing molding of illumination, column is located at D1 layers of skeleton intersection Place；The section of column is square, and the D1 layers of stereoscopic effect being superimposed with D2 layers are as shown in figure 15.Hoistable platform declines a thickness, Barrel is fed again, liquid level is made to rise to chamber top；Irradiation optical system feed liquid liquid level, feed liquid press the figure curing molding of illumination, Such as Figure 10, the D3 layer on D2 layers is molded, D3 layers of structure is consistent with D1 layers, and in terms of overlook direction, D1 layers and D3 layers completely It is overlapped.In C formable layer, feed liquid is filled with the space between B layers of column, and therefore, the buoyancy of feed liquid supports C layers of skeleton Overhanging portion, in edge, the overarm of column is stretched out in the buoyancy support of feed liquid, is avoided overarm or cantilever from collapsing, can be molded The three-dimensional engraved structure that no overarm (or cantilever) collapses, deforms, engraved structure increase the attachment surface of active material (such as cell) Product.Hoistable platform declines a thickness, then prints one layer of column array ..., in this way, forming one layer of grid layer one as shown in Figure 1 The three-dimensional engraved structure of layer column array layer.In two layers adjacent of printing, first the remaining feed liquid after photocuring can be discharged Recycling afterwards, being also possible to directly feed carries out next layer of printing.

When feeding to same material, it can be a barrel and complete；It is also possible to one group of barrel to complete, one group of material Multiple barrels in cylinder are from different location to intracavitary feed.In some embodiments, a kind of method of 3D printing, this method are suitable For having in each layer, there are two types of materials, comprising:

1) prepare 3D printing system and feed liquid, input print out task, feed liquid is packed into the barrel for undertaking feed task, material Expect that A is packed into barrel A, material B is packed into barrel B, barrel A and barrel B is installed in place；

2), hoistable platform is in one thickness of intracavitary decline；

3), as printed material A first in print out task, printed material B again, barrel A is to intracavitary feed, and materials A is full of liter The space that drop platform and chamber surround；

4), optical system completes the solidification of materials A to materials A photocuring；Hoistable platform is in one thickness of intracavitary decline；

5A), judge that print out task, there are also material B not to complete:

5A1), materials A is drained, hoistable platform is made to rise a thickness；

5A2), to intracavitary injection material B, the liquid level of material B is flushed with the top surface of chamber；

5A3), optical system is to material B photocuring；

5A4) all material of current layer is completed to print；Liquid material B is drained, hoistable platform declines a layer It is thick；The latter thickness is as current print out task；Repeat step 3) -5A).In some embodiments, this Method of printing is realized Same layer is made of two kinds of different materials.The space that the feed liquid injected each time is each filled with hoistable platform and chamber surrounds, at feed liquid In in the focusing range of optical system.

For printing three-dimensional engraved structure as shown in Figure 1, which is in by grid layer and column array Interval composition.When the same layer of the engraved structure is made of different materials (when such as printing biologic-organ, in same layer simultaneously Musculature and vascular tissue, the material for printing musculature are different with the material of vascular tissue), two kinds of materials are packed into respectively Barrel A and barrel B (or barrel group A and barrel group B), barrel is with liquid to intracavitary feed.When initial, hoistable platform and chamber Top surface flushes.When initial, hoistable platform is flushed with the top surface of chamber.Ready-to-print first layer, hoistable platform decline a thickness, material Cylinder A feed, irradiation optical system feed liquid liquid level, feed liquid press the figure curing molding of illumination, and such as Figure 12 molds the master of grill-shaped Body (indicates musculature), and main body includes orthogonal grizzly bar, grizzly bar X-shape pore-forming；After molding, by the remaining feed liquid of materials A Discharge；Hoistable platform resets a thickness, barrel B feed, irradiation optical system feed liquid liquid level, material after declining a thickness again Liquid presses the illumination figure curing molding of first layer, and such as Figure 12 forms the wall (indicating vascular tissue) for surrounding of portalling.First layer is beaten Print task is completed, and the remaining feed liquid of material B is discharged.The ready-to-print second layer, hoistable platform decline a thickness, and barrel A is supplied Material molds the main body (indicating muscle) of column array, and column is located at the grizzly bar infall of first layer.After molding, by materials A Remaining feed liquid discharge；Hoistable platform resets a thickness, barrel B feed, irradiation optical system material after declining a thickness again Liquid liquid level, feed liquid press the illumination figure curing molding of the second layer, and the surface forming of each column goes out wall (indicating vascular tissue), In overlook direction, the wall of first layer and the wall of the second layer are overlapped；The print out task of the second layer is completed, the heels of material B Liquid discharge.It is identical as first layer at the forming method and illumination pattern of third layer；4th layer of forming method and illumination pattern with The second layer is identical；... the forming method and illumination pattern of odd-level are identical as first layer；The forming method of even level and illumination Pattern is identical as the second layer.Odd-level replaces with even level, and printing forms every layer of space hollow out knot with different materials tissue Structure.When extending to the case where same layer is formed using two or more materials, as long as preparing corresponding barrel, having formed one every time After kind material, hoistable platform is made to be maintained at the position of equivalent layer, recycling controls illumination figure to form desired structure.

The sequence of each material has been set in step 3), in print out task, then step 3) -5A) molding sequence according to pre- If sequence carries out.Alternatively, not arranging the sequence of a variety of materials in print out task in step 3), then take a kind of material first at random Printing, the printing until completing all material.

In some embodiments, a kind of method of 3D printing, this method are suitable for each layer and there was only a kind of material, but entire It organizes by (such as including materials A, the material B, material C) of two or more material, method includes the following steps:

1) prepare 3D printing system and feed liquid, input print out task, feed liquid is packed into the barrel for undertaking feed task, material Expect that A is packed into barrel A, material B is packed into barrel B, and material C is packed into barrel C, barrel A, barrel B and barrel C is installed in place；

2), hoistable platform is in one thickness of intracavitary decline；

3) current print out task, is identified, printed material A in print out task, barrel A are to intracavitary feed, and materials A is full of lifting The space that platform and chamber surround；

4), optical system completes the solidification of materials A to materials A photocuring；Hoistable platform in one thickness of intracavitary decline, Uncured materials A is drained, next layer is read and is used as current print out task；

5B1), current print out task is identified, such as, in print out task printed material B, barrel B are filled to intracavitary feed, material B The space that full hoistable platform and chamber surround；Optical system completes the solidification of material B to material B photocuring；Hoistable platform is intracavitary Decline a thickness, uncured material B is drained, reads next layer and be used as current print out task；

5B2), current print out task is identified, such as, in print out task printed material C, barrel C are filled to intracavitary feed, material C The space that full hoistable platform and chamber surround；Optical system completes the solidification of material C to material C photocuring；Hoistable platform is intracavitary Decline a thickness, uncured material B is drained, reads next layer and be used as current print out task；

In this way, identifying material in current print out task every time, it is fed, solidified, drain, until all print out task are complete At.

In some embodiments, a kind of method of 3D printing, this method are suitable for each layer and there was only a kind of material, but entire It organizes by (such as including materials A, the material B) of two or more material, still, continuous N number of thickness is materials A；It should Method the following steps are included:

2), hoistable platform is in one thickness of intracavitary decline；

5) it, reads next layer and is used as current print out task, judge that current print out task, current layer use materials A, then barrel A feed；Optical system completes the solidification of materials A to materials A photocuring；Hoistable platform is in one thickness of intracavitary decline；..., In this way, until all layers of printing of continuous use materials A are completed；

6) it, reads next layer and is used as current print out task, judge current print out task, current layer using material B, then by material The residual liquid of material A exhausts, barrel B feed；Optical system completes the solidification of material B to material B photocuring；Hoistable platform exists One thickness of intracavitary decline；..., in this way, until all layers of printing of continuous use material B are completed；

Step 6) is repeated, until completing all print out task.

For example, the epidermis of skin and the tissue of skin corium are different, therefore, form the material used when printing skin It is different.For printing structure as shown in Figure 1.Front N layers of expression skin corium, the material that skin corium uses are identical (as used Materials A).Layer later indicates that epidermis, the material that epidermis uses are identical (as used material B).But corium layer material and table Cortical material is different.As shown in figure 13, when molding, first N layers forms (either grid layer or column array using materials A Layer)；After first N layers has printed, N+1 layers start, and need to form using material B, before N+1 layers of feed, by the residual of materials A The discharge of clout liquid, then material B injection is intracavitary, and liquid level is made to reach chamber top；Form N+1 layers；Layer later uses material B to beat It is printed as type.

As shown in figure 14, it is combined with above two method, prints tooth.Tooth has enamel, dentine and dental pulp, tooth The tip of a root of root only has dentine, followed by several layers dentine outside, including dental pulp；Followed by several layers enamel in outer tooth sheet Matter is including intermediate, dental pulp；It is finally that several layers only have enamel.In these material properties of simulation printing nature tooth, from Root of the tooth to the direction of corona form when, e.g., use material C as enamel, materials A as dentine, material B as dental pulp.

In some embodiments, for example, printing dentine several layers and dentine, dental pulp several layers.A kind of 3D is beaten The method of print, this method are suitable for having some layers there was only a kind of material (such as materials A), and there are also some layers to use multiple material (such as A and B)；It is entire to organize by two or more material；Method includes the following steps:

2), hoistable platform is in one thickness of intracavitary decline；

6) it, reads next layer and is used as current print out task, current print out task (current layer uses materials A and B), material B It first prints, then the residual liquid of materials A exhausts, barrel B feed；Optical system completes the solidification of material B to material B photocuring； Hoistable platform is in one thickness of intracavitary decline；Hoistable platform is set to rise a thickness, the residual liquid of material B exhausts, and barrel A is supplied Material；Optical system completes the solidification of materials A to materials A photocuring；

Repeat step 5) -6), until completing all print out task.

In some embodiments, for example, printing enamel several layers and dentine, dental pulp and enamel several layers, Use material C as enamel, materials A as dentine, material B as dental pulp.A kind of method of 3D printing, this method are suitable For each layer, there are many materials, and a tissue (such as includes materials A, material B, material by two or more material C), method includes the following steps:

2), hoistable platform is in one thickness of intracavitary decline；

3), identify that current print out task, current layer only have a kind of material C, barrel C is to intracavitary feed, and materials A is full of liter The space that drop platform and chamber surround；

4), optical system completes the solidification of material C to material C photocuring；Hoistable platform in one thickness of intracavitary decline, Remaining feed liquid will be discharged, read next layer and be used as current print out task；

5A1), identify current print out task, include materials A, B and C in print out task, it is assumed that material B first print (including The case where sequence of setting and random selected material B are first printed in task)；For barrel B to intracavitary feed, material B is flat full of lifting The space that platform and chamber surround；Optical system completes the solidification of material B to material B photocuring；Remaining feed liquid, hoistable platform is discharged In one thickness of intracavitary decline, then hoistable platform is made to rise a thickness, that is, returns to height when material B feed；

5A2), the space that barrel C is surrounded to intracavitary feed, material C full of hoistable platform and chamber；Optical system is to material C Photocuring completes the solidification of material C, at this point, all material of current layer is completed to print；Hoistable platform is in intracavitary decline one Remaining feed liquid is discharged in thickness, reads next layer and is used as current print out task；

5A3), the space that barrel A is surrounded to intracavitary feed, materials A full of hoistable platform and chamber；Optical system is to materials A Photocuring completes the solidification of materials A, at this point, all material of current layer is completed to print；Hoistable platform is in intracavitary decline one Remaining feed liquid is discharged in thickness, reads next layer and is used as current print out task；Repeat step 5A1) -5A3), until completing currently to beat The all material of print task；

Repeat step 3) -5A3), until completing all print out task.

In some embodiments, as shown in figure 15, for example, when print certain tissue when, have specific one or it is several not It asks, forms the material at these positions other than material of main part, but also need to add specified other materials.For example, printing flesh When meat tissue, there is specific position to need to have high activity, and active site also needs in musculature in natural diffuseness Non-uniform mixing state, therefore, on the basis of musculature, it is also necessary to add the high activity factor (such as stem cell)

A kind of method of 3D printing, this method include materials A (indicating musculature) and material B suitable for a certain layer (indicating high activity factor solutions), and material B is located at the designated position of materials A, and materials A is merged with material B；This method packet Include following steps:

2), hoistable platform is in one thickness of intracavitary decline；

3), barrel A supplies quantitative materials A, and barrel B is adjusted to designated position by position regulator, and barrel B supply is fixed The material B of amount；Barrel A and barrel B provide current layer reduction of feed volume jointly；

4), optical system is to current layer feed liquid photocuring.

Material B is instilled in materials A, natural disperse state is formed, so as to print two kinds of material natural diffuseness Non-uniform mixing system.

Material, feed liquid

The material or feed liquid refer to a kind of material or mixed for being processed by printer in the present invention Close object.When being processed with 3D printer of the invention, existing some biomaterials can be used for printing. For example, many materials include natural polymer: collagen, silk fiber, gelatin, alginate and synthetic polymer: polyethylene glycol (PEG) or their any one mixing can be used for printer of the invention and be processed.These are as biological 3D printing Material, also referred to as " bio-ink ".Although material itself belongs to traditional material, it can all use and be distributed bright printing Device and method are printed.The biomaterial of this printing has solid space structure, or has space-time, Ke Yishe Set arbitrary through-hole.Here through-hole generally refers to the structure of plane or the structure of solid.For example, having in the plane Hole, the shape in this hole can be any shape, round, rectangle, square, diamond shape etc..When multiple faces are in different dimensions On, it is formed three-dimensional shape, each face of three-dimensional shape or the porose structure of multiple masks, and this some holes all has one Fixed depth can be communicated between each hole here, can also be not communicated with, or part communicates, and material is thus formed through whole The channel of a stereochemical structure or part isometric structure.Such structure is easy to accomplish using printer of the invention.

In some modes, barrel is the container for accommodating different materials, and different barrels can be used for containing same material Material.Optionally, different material or bio-ink can be held in barrel, such as barrel A holds a kind of biomaterial, expect Cylinder B holds another biomaterial, the property of two kinds of materials be not it is the same, using printing technique of the invention, Ke Yishi The printing of existing complex biological tissue or organ.This is because a kind of biomaterial or organ, it is not uniform for being in structure It is consistent, but with the difference in structure or biological property.For example, the skin material of mammal, with epidermis, very The structure of skin, the tissue that corium has blood vessel and connect with muscle, these different parts is different, and thickness is different, and there are also each Excessive structural between tissue is also different, and this difference further includes density, aperture etc..In this way, passing through biography if necessary The printing of system is printed, and all structures or tissue are the same, and printing technique through the invention, can be primary Property carry out different structure biomaterial.

In some modes, material described in the present invention can be mixed with stem cell to be processed or is printed, this Sample, material is as supporting structure, and cell can be broken up as active cost, finally, form active tissue.When So, supporting structure can also be printed, then allows stem cell to be filled in the space of skeleton and goes, finally also forms tissue living.

It newly-designed is printed into any suitable material can be printed in short, of the invention.

In some specific modes, the present invention provides a kind of new 3D printing bio-ink, also known as new material.One In some specific modes, it includes that photoresponse is handed over that the present invention, which provides a kind of light-operated 3D printing bio-ink or material, the material, Join the macromolecular of base group modification, the macromolecular of adjacent nitro benzyl class light trigger modification, photoinitiator.In some instances, it also wraps Include water, such as deionized water.In fact, before the printing, biomaterial of the invention is actually a kind of basic material, when need When printing, it can be mixed with solvent and form the state of solution or the state of fluid, and the basic material can be Dry form exists.It is stored it is of course also possible to directly be made into liquid form.Optionally, so as " bio-ink " A kind of basic material.

In some preferred modes, the macromolecular and adjacent nitro benzyl class light trigger of the photoresponse crosslinked group modification The macromolecular quality final concentration of modification is 0.1~10% with deionized water meter.

In some preferred modes, the photoinitiator quality final concentration is calculated as 0.001 with deionized water amount~ 1%.

In some preferred modes, photoresponse crosslinked group is connect in the macromolecular of the photoresponse crosslinked group modification Branch Replacement rate is 10~90%, and photoresponse crosslinked group is Methacrylamide, and methacrylic anhydride, Glycidyl methacrylate is sweet Grease or acryloyl chloride.

In some preferred modes, adjacent nitro benzyl class light in the macromolecular of the adjacent nitro benzyl class light trigger modification The grafting Replacement rate of trigger is 1~100%.

In some preferred modes, further, the macromolecular such as formula (I) of the adjacent nitro benzyl class light trigger modification It is shown, in formula (I), R₁For-H or it is selected from-CO (CH₂)xCH₃、-CO(CH₂CH₂O)_xCH₃、 -CO(CH₂)_x(CH₂CH₂O)_yCH₃'s Ester bond class is selected from-(CH₂)_xCH₃、-(CH₂CH₂O)_xCH₃、 -(CH₂)_x(CH₂CH₂O)_yCH₃、Ehter bond class, be selected from-COO (CH₂)_xCH₃、 -COO(CH₂CH₂O)_xCH₃、-COO(CH₂)_x(CH₂CH₂O)_yCH₃Carbonic acid ester bond class, be selected from-CONH (CH₂)_xCH₃、-CONH(CH₂CH₂O)_xCH₃、-CONH(CH₂)_x(CH₂CH₂O)_yCH₃Isocyanic acid ester bond class, wherein x and y >=0 and to be whole Number；R₂For-H or it is selected from-O (CH₂)_xCH₃、 -O(CH₂CH₂O)_xCH₃、-O(CH₂)_x(CH₂CH₂O)_yCH₃Substituent group, wherein x and y >=0 and be integer；R₃Selected from amino connecting key-O (CH₂)_xCONH(CH₂)_yNH-, halogenated class connecting key-O (CH₂)_xAnd carboxyl Class connecting key-O (CH₂)_xCO-, wherein x and y >=1 and be integer；R₄For-H or-CONH (CH₂)_xCH₃, wherein x >=0 and to be whole Number；P₁For macromolecular；

In some preferred modes, the macromolecular and adjacent nitro benzyl class light trigger of the photoresponse crosslinked group modification Natural biological macromolecular in the macromolecular of modification is glucan, hyaluronic acid, gelatin, sodium alginate, chondroitin sulfate, silk Element, chitosan, carboxymethyl cellulose or collagen, one of polyethylene glycol or lemon acid polymer (PEGMC).

In some preferred modes, the photoinitiator is 2- hydroxyl -4'- (2- hydroxy ethoxy) -2- methyl phenyl ketone (2-Hydroxy-4'- (2-hydroxyethoxy) -2-methylpropiophenone, I2959) or phenyl (2,4,6- tri- Methyl benzoyl) phosphoric acid lithium salts (lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP) One of；The mass ratio of the macromolecular of the photoinitiator and the graft modification of photoresponse crosslinked group is 1~3:100.

In some preferred modes, the grafting Replacement rate of the macromolecular of photoresponse crosslinked group modification is 10~ 30%；The grafting Replacement rate of the macromolecular of the adjacent nitro benzyl class light trigger modification is 1~20%.

In some preferred modes, it is 10% that the macromolecular of the photoresponse crosslinked group modification, which is grafting Replacement rate, Methacrylic anhydride modification gelatin, grafting Replacement rate be 90% the amine-modified gelatin of methacryl, grafting Replacement rate The amine-modified gelatin of the methacryl that gelatin, grafting Replacement rate for 40% methacrylic anhydride modification are 20%, grafting The sulfuric acid for the methacrylic anhydride modification that collagen, the grafting Replacement rate for the methacrylic anhydride modification that Replacement rate is 30% are 90% The amine-modified carboxymethyl cellulose of the methacryl that chondroitin or grafting Replacement rate are 10%, grafting Replacement rate are the third of 10% The polyethylene glycol of alkene acyl chlorides modification, one in glucan that the glycidyl methacrylate that grafting Replacement rate is 20% is modified Kind.

In some preferred modes, the macromolecular of the adjacent nitro benzyl class light trigger modification is that grafting Replacement rate is The sodium alginate for the adjacent nitro benzyl modification that hyaluronic acid, the grafting Replacement rate of 100% adjacent nitro benzyl modification are 50% connects The adjacent nitro benzyl modification that chondroitin sulfate, the grafting Replacement rate for the adjacent nitro benzyl modification that branch Replacement rate is 10% are 30% Gelatin, grafting Replacement rate be 90% adjacent nitro benzyl modification fibroin, grafting Replacement rate be 100% adjacent nitro benzyl repair The chitosan that the adjacent nitro benzyl that the collagen or grafting Replacement rate of decorations are 10% is modified, the lemon of 10% adjacent nitro benzyl modification One of acid polymer (PEGMC).

In some preferred modes, the macromolecular quality final concentration of the photoresponse crosslinked group modification is with deionized water Quality meter is 3-10%, and the macromolecular quality final concentration of adjacent nitro benzyl class light trigger modification is calculated as 2- with deionized water amount 4%, the photoinitiator quality final concentration is calculated as 0.03-0.2% with deionized water amount.

The present invention generates aldehyde radical after illumination excitation using adjacent nitro benzyl class light trigger, and the aldehyde radical and amino of generation can Reaction forms the principle of powerful chemical key, meanwhile, the macromolecular of photoresponse crosslinked group modification solidifies rapidly under light illumination, double cross Network of networking enhances mechanical property, and it is a kind of ideal that the porous precise and tiny structure of 3D printing, which can achieve the purpose that quick repair deficiency, The light-operated 3D printing ink for defect of skin or osteochondral defect reparation.Here material can exist in any form, Can exist in the form of solid, when needed, the form for being configured to liquid carries out printing processing, or is directly configured to The form of liquid waits when printed, directly carries out printing processing.

Herein, material and bio-ink can be interchanged, and can be referred to as material generally as the substance of printing processing, Can also being referred to as ink or bio-ink, perhaps bio-ink material material here or ink may include some work Including property ingredient, such as stem cell or cell or other compositions, certainly, also only material or ink itself are beaten Print or processing, it is also possible then to add active constituent again.

Specific implementation

The present invention provides specific embodiment and illustrates Method of printing and used bio-ink material of the invention, can To understand, these examples are only that can not constitute to the present invention any to how to realize that the present invention is further explained Limitation, the scope of the present invention are subject to claim.

Embodiment 1: the skin of the 3D printing for injury repair

Such as shown in Figure 10,11 and 12 and 13, first the material printed is modeled, the model then more established Process control is carried out, is then printed.Such as the model of foundation is as illustrated in figs. 10 and 12, Figure 10 is the model of corium, Figure 12 For epidermis with corium group together with.Figure 11 is the print procedure schematic diagram for 3 layers.For example, the expression needs of black are beaten The bracket of print, the structure of similar Three-dimentional square body, and the bracket that the use of 12 sides of bracket is printed, and the formed hollow out of bracket Stereochemical structure 102, form the unit of a print carriage, multiple units combinations are formed the porous knot of overarm form Structure.Entire unit can form the dermis scaffold of arbitrary dimension, such as can be diameter is 8 millimeters, and epidermis with a thickness of 1 Millimeter, and corium with a thickness of 1 millimeter, material is thus formed the skins of 2 mm of thickness.Being designed to double-layer structure is to simulate The epidermis and skin corium of skin, epidermis compact structure, skin corium short texture, therefore superstructure is designed to solid cylinder Body, understructure are designed to that cantilever beam porous structure, suitable cell Proliferation, Differentiation and blood vessel are grown into.

And the proportion of material used by supporting structure is as follows: the gelatin (GelMA) and N- of methacrylic anhydride grafting The grafting of (2- aminoethyl) -4- (- the 5- of 4- (methylol) -2- methoxyl group nitroso containing phenoxy group) butyramide (NB) it is transparent Matter acid (HA-NB).The two concentration is to be respectively as follows: 2.5% and 0.625%, and photosensitizer concentration is the 2% of total volume, phenol red concentration 0.4%, remaining ingredient is water.

It uses biomaterial according to model as shown in Figure 10, describe for 3 layers the process (Figure 13) of printing, as follows:

Material used by supporting structure is packed into barrel by step 1, and when initial, hoistable platform is flushed with the top surface of chamber；

Step 2, hoistable platform decline a thickness, and biomaterial is injected intracavitary, biomaterial liquid level and chamber by barrel Top surface flush, irradiation optical system feed liquid liquid level, optical figuring is grid, and biomaterial solidifies, forms grid after illumination First layer A；

Step 3, hoistable platform decline a thickness, and biomaterial is injected intracavitary, biomaterial liquid level and chamber by barrel Top surface flush, irradiation optical system feed liquid liquid level, optical figuring be column array, column be located at first layer grizzly bar intersect Place, biomaterial solidifies, is formed the second layer B of column array after illumination；

Step 4, hoistable platform decline a thickness, and biomaterial is injected intracavitary, biomaterial liquid level and chamber by barrel Top surface flush, irradiation optical system feed liquid liquid level, optical figuring be with first layer identical grid, biological material solid after illumination Change, formed the third layer C of grid；In third formable layer, biomaterial is filled with the space between the column of the second layer, because This, the buoyancy of biomaterial supports the overhanging portion of third layer grizzly bar, and in edge, column is stretched out in the buoyancy support of feed liquid Grizzly bar and form overarm, avoid that overarm, overhanging portion collapses；Later the step of, column array layer and grid layer alternately form, at Type goes out the three-dimensional engraved structure that nothing as shown in Figure 10 is collapsed, deformed.The light intensity 50 of all of above printing, the time for exposure: 1000ms。

Print result pictorial diagram as shown in figure 14 is the pictorial diagram of dermis.Wherein, it is seen in microstructure, from true The top view of skin can be seen that the structure (structure 101 in similar window or hole) with similar hollow out, Figure 15 A, and solid be Supporting structure 104 is the bracket for forming hole or window, Figure 15 B.

It can be seen that in total focal microstructure from Figure 16 A-16C, light beam is the supporting structure 101 of this printed material, and In the internal structure with building sky 104.With three-dimensional space structure, moreover, the light beam of grey indicates skeleton structure 104, and And there is space in the surrounding of each light beam, form a three-dimensional space structure, the solid space solution structure of the three-dimensional In may include stem cell or active constituent, conducive to the mitogenetic of cell, so that printing just has more bioactivity.

As illustrated in figures 17 a-17 c, using there is fibroblast in the supporting structure of this Method of printing printing, in culture 1 Zhou Hou still has 95% cell to have bioactivity, and Figure 17 A is the fluorogram for the photo that entire fibroblast survives, figure The fluorescence of the cell of 17B death is in phasor, and Figure 17 C is the image survived with dead cell fit.It can be seen from the figure that dead The cell died is considerably less.After cultivating 15 days, survival rate 90%, after culture 20 days, survival rate 88%, after culture 1 month, Survival rate is 85%.

And the material for using traditional printing technique to print, cell mortality is very high, cultivates after a week, general death rate 90% or more, and the time survived is very short, and most 2-4 days times cannot specifically apply in practice substantially.

It is appreciated that can only be merely printing corium, the size of corium be determined, corium based on the big lower of wound is repaired After printed, corium is covered on wound, is then coated with one layer of epidermis, then by photocuring, to repair wound.Corium In can have fibrocyte or other active constituents.

Embodiment 2:3D prints repair of cartilage

Such as shown in Fig. 1,18, first the material printed is modeled, program is then carried out according to the model of foundation Control, is then printed.Such as the model of foundation, as shown in Fig. 1 and 18, Figure 18 is the model of cartilage frame, including upper Layer bracket 901 and lower floor support 902, wherein upper layer bracket is 30 circular holes 900, and also there are 30 circular holes 903, Ge Geyuan in side Hole intersection is identical, such as the circular hole 903 of each circular hole 900 and side above communicates, such as Fig. 1 can see.Branch The diameter dimension of frame is 4 millimeters, and upper thickness is 1 millimeter, and lower thickness is 2 millimeters.Actually also have in lower layer corresponding 30 holes are identical as 30 holes on upper layer, and the hole of next not side.

Design is that with the bracket, lower floor support top view is to have 30 holes, it is therefore an objective to be for repair of cartilage in this way Mesenchymal stem cell is migrated to upper layer, facilitates the reparation of cartilage.Upper layer bracket design, intermediate hole between marrow in order to fill Matter stem cell migrates to cartilage layers, and side hole migrates for cartilage cell to injury region, preferably repairs cartilage defect.It is added KGN small molecule can maintain chondrocyte phenotype, promote mesenchymal stem cell to Chondrocyte Differentiation.

The proportion of material used by supporting structure is as follows: upper and lower level is the gelatin of 8M methacrylic anhydride grafting (GelMA), concentration 15%.Photosensitizer is 10%v/v, phenol red concentration 0.8%.KGN small molecule is added in upper layer bracket, finally Diluted concentration is 50uM.

It uses biomaterial according to model as shown in figure 18, describe for 3 layers the process (Fig. 1) of printing, as follows: with It is as follows according to the process of the Method of printing of cartilage frame model using biomaterial for gradually increasing material molding from bottom to top:

Step 1 is sliced cartilage frame model by thickness, illumination figure of the figure of every layer of slice as this layer；It will give birth to Object material is packed into barrel, and when initial, hoistable platform is flushed with the top surface of chamber；

Step 2, hoistable platform decline a thickness, and biomaterial is injected intracavitary, biomaterial liquid level and chamber by barrel Top surface flush, optical system by current layer illumination figure irradiate feed liquid liquid level, illumination figure position corresponding with through-hole without Light covering, biomaterial solidification, formation first layer after illumination；Step 2 is repeated, until completing lower floor support；

Step 3, print upper layer bracket radial through-hole lower half circular arc when, repeat step 2；

Step 4, when printing the upper half circular arc of upper layer bracket radial through-hole, a rear printable layer relatively before primary printing Layer is prominent and suspending part occurs, and hoistable platform declines a thickness, and biomaterial is injected intracavitary, biomaterial liquid level by barrel It is flushed with the top surface of chamber；In the inner wall of radial through-hole, preceding primary printing, the support of the feed liquid of uncured biomaterial is current Layer suspending part, avoid suspending part from collapsing, thus print inner wall be in accurate circular arc radial through-hole, repeat step 3 and 4, the printing until completing upper layer bracket.The light intensity 50 of all of above printing, time for exposure: 1000ms.

As shown in figure 20, the mechanism map in kind of the supporting structure of this Method of printing printing is utilized.Figure 19 is each layer aobvious Micro-structure figure, wherein the top view of different pore sizes can be seen that between side opening and the hole of vertical view aligned identical each other.Together The fluorescence structure figure of Shi Caiyong fluorescence microscopy microscopic observation 400um.

In the case where lacking any element specifically disclosed herein, limitation, may be implemented illustrated and described herein Invention.Used terms and expressions method is used as the term of explanation rather than limits, and is not intended in these terms and table Up to any equivalent for excluding shown and described feature or part thereof in the use of method, and it should be realized that various remodeling exist It is all feasible in the scope of the present invention.It is therefore to be understood that although specifically being disclosed by various embodiments and optional feature The present invention, but the modifications and variations of concept as described herein can be used by those of ordinary skill in the art, and recognize It is fallen into for these modifications and variations within the scope of the present invention of the appended claims restriction.

It is described herein or record article, patent, patent application and every other document and can electronically obtain The content of information to a certain extent in full include herein by reference, just as each individual publication by specific and single Solely point out by reference.Applicant retains from any of any this article, patent, patent application or other documents And all material and information are incorporated into the right in the application.

Claims

1. one kind is used for light-operated 3D printing biomaterial, the material includes the macromolecular of photoresponse crosslinked group modification, adjacent nitre The macromolecular of base benzyl class light trigger modification, photoinitiator.

2. biomaterial according to claim 1, wherein further include deionized water.

3. biomaterial according to claim 2, wherein the macromolecular and adjacent nitro of the photoresponse crosslinked group modification The macromolecular quality final concentration of benzyl class light trigger modification is 0.1~10% with deionized water meter.

4. biomaterial according to claim 3, wherein the photoinitiator quality final concentration is with deionized water meter It is 0.001~1%.

5. according to biomaterial described in claim 3 or 4, wherein in the macromolecular of the photoresponse crosslinked group modification The grafting Replacement rate of photoresponse crosslinked group is 10~90%.

6. biomaterial described in one of -5 according to claim 1, wherein photoresponse crosslinked group is Methacrylamide, first Base acrylic anhydride, one of glycidyl methacrylate or acryloyl chloride or several.

7. biomaterial described in one of -6 according to claim 1, wherein big point of the adjacent nitro benzyl class light trigger modification The grafting Replacement rate of adjacent nitro benzyl class light trigger is 1~100% in son.

8. biomaterial according to claim 7, wherein the macromolecular such as formula of the adjacent nitro benzyl class light trigger modification (I) shown in, in formula (I), R₁For-H or it is selected from-CO (CH₂)xCH₃、-CO(CH₂CH₂O)_xCH₃、-CO(CH₂)_x(CH₂CH₂O)_yCH₃ Ester bond class, selected from-(CH₂)_xCH₃、-(CH₂CH₂O)_xCH₃、-(CH₂)_x(CH₂CH₂O)_yCH₃、Ehter bond class, be selected from-COO (CH₂)_xCH₃、-COO(CH₂CH₂O)_xCH₃、-COO(CH₂)_x(CH₂CH₂O)_yCH₃Carbonic acid ester bond class, be selected from-CONH (CH₂)_xCH₃、-CONH(CH₂CH₂O)_xCH₃、-CONH(CH₂)_x(CH₂CH₂O)_yCH₃Isocyanic acid ester bond class, wherein x and y >=0 and to be whole Number；R₂For-H or it is selected from-O (CH₂)_xCH₃、-O(CH₂CH₂O)_xCH₃、-O(CH₂)_x(CH₂CH₂O)_yCH₃Substituent group, wherein x and y >=0 and be integer；R₃Selected from amino connecting key-O (CH₂)_xCONH(CH₂)_yNH-, halogenated class connecting key-O (CH₂)_xAnd carboxyl Class connecting key-O (CH₂)_xCO-, wherein x and y >=1 and be integer；R₄For-H or-CONH (CH₂)_xCH₃, wherein x >=0 and to be whole Number；P₁For macromolecular；

9. biomaterial according to claim 7, wherein the adjacent nitro benzyl class light trigger is adjacent nitro benzyl.

10. biomaterial according to claim 1, wherein the macromolecular and adjacent nitro of photoresponse crosslinked group modification Benzyl class light trigger modification macromolecular in natural biological macromolecular be glucan, hyaluronic acid, gelatin, sodium alginate, One in chondroitin sulfate, fibroin, chitosan, carboxymethyl cellulose or collagen, polyethylene glycol or lemon acid polymer (PEGMC) Kind.

11. application of the light-operated 3D printing biomaterial described in a kind of one of claim 1-10 in skin injury reparation.

12. light-operated 3D printing biomaterial answering in Articular cartilage repair described in a kind of one of claim 1-10 With.