CN111317589B - Manufacturing method of gum expander - Google Patents
Manufacturing method of gum expander Download PDFInfo
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- CN111317589B CN111317589B CN201911202269.7A CN201911202269A CN111317589B CN 111317589 B CN111317589 B CN 111317589B CN 201911202269 A CN201911202269 A CN 201911202269A CN 111317589 B CN111317589 B CN 111317589B
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- dilator
- monomer
- gum
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C19/00—Dental auxiliary appliances
- A61C19/06—Implements for therapeutic treatment
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- Health & Medical Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Dentistry (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a manufacturing method of a gum expander, which comprises the following steps of (1) adopting a titanium metal bracket of a 3D printed gum expander; (2) and preparing the hydrogel: the preparation method of the hydrogel comprises the following steps of firstly, purifying required reagents according to the types, wherein liquid reagents are purified by distillation, and solid reagents are purified by a recrystallization method; step two, uniformly mixing monomer MMA, monomer NVP and initiator AIBN; adding a conventional cross-linking agent AMA into the pipette and shaking up; adding a conventional cross-linking agent EGDM into a liquid transfer gun, shaking up, ultrasonically oscillating and filtering; and fifthly, subpackaging the dried gingiva dilator and the titanium metal bracket together into a self-made glass grinding tool, putting the self-made glass grinding tool into a vacuum drying oven, and heating the self-made glass grinding tool by gradient heating to obtain the gingiva dilator with the dry self-made hydrogel. The gum dilator manufactured by the invention can be suitable for dilating soft tissues in the oral cavity, is particularly suitable for dilating gums, and is convenient to fix.
Description
Technical Field
The invention relates to the technical field of medical instruments, in particular to a manufacturing method of a gum dilator.
Background
The treatment of partial maxillofacial diseases is often based on sufficient soft tissues, and for example, periodontal surgery, guided alveolar bone regeneration surgery all depend on gingival tissues, cleft lip and palate repair, maxillofacial scar reshaping and the like, and the sufficient soft tissues are expected. The current solutions to the above problems are mainly surgical operations, and the common surgical methods are distraction, flap rotation, gum transplantation, tissue flap transplantation, and the like. These surgical procedures place high technical demands on the physician and are frequently associated with complications. In addition, the problem of insufficient soft tissue can be solved to a certain extent by using non-surgical operations, for example, the prosthesis is manufactured to restore partial functions and shapes; the non-conventional implant, the short implant, the overlong zygomatic implant and the like are used on the alveolar bone which has insufficient bone mass and can not be used for guided bone tissue regeneration.
The first generation of soft tissue expanders, mainly balloon expanders made of elastic silica gel, are currently used more in burn and plastic surgery department and can also be used on the skin of the jaw and face, but are used less in the mouth, and few scholars use traditional expanders to expand the gum in the mouth. The traditional balloon dilator is difficult to adapt to complex shapes in the mouth due to single shape and an external water injection or inflation pipeline. The second generation of soft tissue expanders is generally made of synthetic polymer materials, and they expand by osmotic pressure, and have been tried by researchers to expand soft tissues in the mouth. Second generation soft tissue expanders are commonly referred to as osmotic expanders, hydrogel expanders, soft tissue expanders or self-expanding hydrogels, etc., where the nomenclature is not uniform. It is swollen mainly by osmotic pressure without water injection, and the absorbent liquid in vivo swells, and there have been attempts by researchers to use it for the expansion of the skin and gum of the jaw face.
The prior soft tissue dilator is firstly reported in 1957, and is mainly based on a silica gel balloon, is connected with a water injection or inflation channel, and dilates the soft tissue by injecting water or inflating air in times. This soft tissue expansion phenomenon is similar to the increase of abdominal skin of pregnant women, the increase of the whole body skin area of obese patients, and the phenomenon of lip, nose and neck skin expansion of a small number of african people. In 1957, Neumann first used a soft tissue expander for augmentation of the temporal occipital skin and then repaired the ear defect caused by trauma. However, almost no reports are found in the following decades, and until the eighties of the 20 th century, Radovan et al have improved the dilator and used for scars, open lesions, breast reconstruction and the like, which arouses the attention of more scholars. Currently, when the dilator is used clinically, the dilator is firstly implanted into the soft tissue to be dilated, then normal saline is injected through a pipeline, the total volume of the dilator is generally injected by 10 to 15 percent each time, and the dilator is injected for 1 to 3 times per week according to the specific situation of a patient. The first generation of soft tissue expanders is suitable for the expansion of skin in the parts with large range and regular shape, such as limbs, trunk, scalp, etc. and has satisfactory clinical effect for many scholars, but is not suitable for the places with complicated shape, such as mouth, etc. and has certain limitation in paediatrics due to the matching problem of patients. The existing soft tissue expanders are occasionally associated with complications such as soft tissue infection, pain, congestion and perforation, expander rupture, etc. The first generation of soft tissue expanders are not suitable for the expansion of soft tissue in the oral cavity, and are particularly not suitable for the expansion of gum, because the shape is single, the gum with large shape difference can not be applied, the external pressurizing pipeline for tubular water injection or gas injection, the junction of the pipeline and the gum is susceptible to infection, the pipeline is easy to be pulled and changed in position, the patient needs to be pressurized by self water injection, the pain is obvious during pressurizing, and the like.
Disclosure of Invention
The invention aims to solve the problems that: provided is a method for manufacturing a gum expander which is suitable for the expansion of soft tissues in the oral cavity, particularly for the expansion of gums, and which is convenient to fix.
The technical scheme provided by the invention for solving the problems is as follows: a method for manufacturing a gingival dilator comprises the following steps,
(1) adopting 3D to print a titanium metal bracket of the gum dilator;
(2) and preparing the hydrogel: the preparation of the hydrogel comprises the following steps,
step one, purifying required reagents according to classes, wherein liquid reagents are purified by distillation, and solid reagents are purified by a recrystallization method;
step two, uniformly mixing monomer MMA, monomer NVP and initiator AIBN, wherein the mass ratio of the monomer MMA to the monomer NVP is 3:1, and the mass of the initiator AIBN is 0.1 percent of the total weight of the monomer MMA and the monomer NVP;
adding a conventional cross-linking agent AMA with the mass being 0.1 percent of the total weight of the monomer MMA and the monomer NVP into the pipette, and shaking up;
adding a conventional cross-linking agent EGDM with the mass being 0.01 percent of the total weight of the monomer MMA and the monomer NVP into a pipette, shaking up, performing ultrasonic oscillation, and performing suction filtration;
and fifthly, subpackaging the dried gingiva dilator and the titanium metal bracket together into a self-made glass grinding tool, putting the self-made glass grinding tool into a vacuum drying oven, and heating the self-made glass grinding tool by gradient heating to obtain the gingiva dilator with the dry self-made hydrogel.
Preferably, the specific process of using the metal bracket of the 3D printed gingival dilator in the step (1) is,
a. carrying out CT scanning on the jaw bone to obtain DICOM data, and preprocessing the image;
b. the MIMICS software reconstructs a complete full-jaw bone three-dimensional model, stores the model in an STL format and performs virtual implantation of a defect area;
c. the method comprises the following steps of designing shapes of a bracket, a screw and a screw hole in Geomagic, and converting a model into an NURBS model;
d. completing the CAD design of the personalized bracket;
e. manufacturing a titanium bracket form suitable for a specific damaged part by a rapid forming technology;
preferably, in the fifth step, the initial temperature of the gradient temperature rise heating is 80 ℃, the temperature is maintained for 24 hours, and finally the temperature is heated for 15min at 120 ℃.
Compared with the prior art, the invention has the advantages that: the compound synthesized by taking Methyl Methacrylate (MMA) and N-vinyl pyrrolidone (NVP) as monomers can be applicable to expanding soft tissues of jaw and face, and the formula and the process can be used as the basis of clinical research; the self-made hydrogel has a uniform porous network structure, uniform pore distribution, an expansion rate of 505.87 +/-3.6 percent, complete expansion within 3-4 days at the initial stage, complete expansion within 1w, and relatively high expansion rate and expansion speed; the hydrogel has the lowest mechanical property after being completely expanded, the compressive strength can reach 1.79 +/-0.20 MPa, the hydrogel is not easy to crack, the integral integrity can be well kept even if the hydrogel is cracked, the clinical mechanical property requirements can be preliminarily met, and the hydrogel is suitable for the expansion of the soft tissues of the maxillofacial region. Energy spectrum analysis proves that the self-made hydrogel mainly contains C, O elements, all the elements are uniformly distributed, and the aggregation phenomenon of some elements does not occur; fourier infrared spectrum analysis proves that the self-made hydrogel contains an amide structure and an ester group, and a vinyl double bond is opened to carry out addition reaction to form a macromolecular compound containing hydrophilic groups; animal experiments prove that the self-made hydrogel has good biocompatibility, can slowly expand in an animal body, has good soft tissue expansion performance, can gradually form a biological envelope at the periphery of the hydrogel, and cannot cause the absorption of bone tissues in an expansion area; preliminary evaluation of the imaging suggests that color ultrasound, CT and MRI can develop the hydrogel, and the boundary between the hydrogel and the surrounding tissues is clear, so that the method can be used for evaluating the expansion condition of the hydrogel in vivo in real time.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention and not to limit the invention.
FIG. 1 is a schematic of the route of hydrogel synthesis according to the present invention;
FIG. 2(A) hydrogel after swelling (left, 1.4cm diameter) and hydrogel in dry state (right, 0.9cm diameter). (B) The x 40 dry hydrogel optical microscopic picture shows that the hydrogel surface is uniform, the structure is complete and continuous and has no obvious defects. (C) And (3) taking an optical microscope picture of the hydrogel after the hydrogel completely absorbs water, wherein the hydrogel contains a large amount of water, is uniform and transparent and has no structural defects. (D) The x 40 hydrogel is completely expanded and then is subjected to vacuum drying, and then the hydrogel is seen in an optical microscope, is in a three-dimensional net shape, is relatively uniformly connected with one another, and has no obvious structural defect;
in FIG. 3, the images of SEM × 200 times, SEM × 1000 times, and SEM 5000 times dry hydrogel are shown, and the dry hydrogel is uniform and dense, and has tens of nanometer pores distributed on the surface under the microscope of SEM × 5000 times. (D) (E) (F) pictures of the hydrogel after complete expansion and vacuum drying under the microscope of SEM multiplied by 200, multiplied by 1000 and multiplied by 5000 respectively, the hydrogel is distributed with a porous structure, all pores are connected into a solid net, and a plurality of small pores are distributed in the large pores and at the joints;
figure 4 is a table of the in-out swelling ratio (n-12) of hydrogel 24 h;
figure 5 is a table of the in-out swelling ratio (n-12) for hydrogel 7 d;
FIG. 6(A) hydrogel 24h in vitro swelling rate; (B) the expansion rate of hydrogel 7d in vitro;
figure 7 is a table of compression strengths (MPa, n-5) for hydrogel of group a (expanded 2d group);
figure 8 is a table of compressive strength (MPa, n-5) for hydrogel of group B (expanded 28d group);
FIG. 9 is a graph showing the result of the spectrum analysis of sample 1;
FIG. 10 is a graph showing the result of the energy spectrum analysis of sample 2;
FIG. 11 is a graph showing the result of the spectrum analysis of sample 3;
FIG. 12 is a graph of acute systemic toxicity grading;
in FIG. 13, A & E are the gross specimen and the under-lens view of the soft tissue of the control group. The B & F are implanted into the 1w group, the soft tissues are swollen, no envelope exists, the hydrogel is complete and has no defects, the hydrogel is easy to separate from the soft tissues, and a large number of inflammatory cells and new vessels appear under the microscope. The C & G implanted 2w group soft tissue has no obvious swelling, a thin layer envelope, complete hydrogel without defect, and occasional hydrogel, a small amount of inflammatory tissue and a small amount of new blood vessels in the envelope under the microscope. The D & H implanted group 4w has no swelling and thickening of soft tissues and no envelope, the hydrogel is complete and has no defect, a fiber envelope is arranged around the visible hydrogel under the microscope, the envelope is continuous and complete, the hydrogel is occasionally seen in the envelope, and inflammatory cells are not seen. E-H is a microscopic image of 100 times, Δ is hydrogel, and → is envelope.
The ultrasound image of the self-expanding hydrogel in FIG. 14 shows (A) the hydrogel has dark areas, no blood flow signal and clear borders. (B) The CT imaging of the self-expanding hydrogel is clearer and is different from the threshold value of the surrounding tissues. (C) The MRI imaging brightness of the self-swelling hydrogel is high, and the boundary with the surrounding tissues is clear.
FIG. 15 is a schematic view of a titanium metal stent;
the attached drawings are marked as follows: 1. screw hole, 2, stationary blade, 3, mount pad, 4, reinforcing bar, 5, activity groove, 6, accommodation hole, 7, installation piece, 8, connecting piece.
Detailed Description
The following detailed description of the embodiments of the present invention will be provided with reference to the accompanying drawings and examples, so that how to implement the embodiments of the present invention by using technical means to solve the technical problems and achieve the technical effects can be fully understood and implemented.
Example 1
A method for manufacturing a gingival dilator comprises the following steps,
(1) adopting 3D to print a titanium metal bracket of the gum dilator;
(2) and preparing the hydrogel: the preparation of the hydrogel comprises the following steps,
step one, distilling and purifying a monomer MMA and a monomer NVP; purifying an initiator AIBN by adopting a recrystallization method;
step two, uniformly mixing 75g of monomer MMA, 25g of monomer NVP and 0.1g of initiator AIBN;
adding 0.1g of conventional cross-linking agent AMA into a pipette and shaking up;
adding 0.01g of conventional cross-linking agent EGDM into a liquid transfer gun, shaking up, performing ultrasonic oscillation, and performing suction filtration;
and step five, subpackaging the dried self-made hydrogel and the titanium metal bracket into a self-made glass grinding tool, placing the self-made glass grinding tool into a vacuum drying oven, performing gradient heating to obtain the gum dilator with the dry self-made hydrogel, performing gradient heating at the initial temperature of 80 ℃, maintaining for 24 hours, and finally heating at 120 ℃ for 15 minutes.
Wherein the specific process of adopting the metal bracket of the 3D printed gum dilator in the step (1) comprises the following steps,
a. carrying out CT scanning on the jaw bone to obtain DICOM data, and preprocessing the image;
b. the MIMICS software reconstructs a complete full-jaw bone three-dimensional model, stores the model in an STL format and performs virtual implantation of a defect area;
c. the method comprises the following steps of designing shapes of a bracket, a screw and a screw hole in Geomagic, and converting a model into an NURBS model;
d. completing the CAD design of the personalized bracket;
e. manufacturing a titanium bracket form suitable for a specific damaged part by a rapid forming technology;
example 2
A method for manufacturing a gingival dilator comprises the following steps,
(1) adopting 3D to print a titanium metal bracket of the gum dilator;
(2) and preparing the hydrogel: the preparation of the hydrogel comprises the following steps,
step one, distilling and purifying a monomer MMA and a monomer NVP; purifying an initiator AIBN by adopting a recrystallization method;
step two, uniformly mixing 90 g of monomer MMA, 30g of monomer NVP and 0.12g of initiator AIBN;
adding 0.12g of conventional cross-linking agent AMA into a pipette and shaking up;
adding 0.012g of conventional cross-linking agent EGDM into a pipette, shaking up, performing ultrasonic oscillation, and performing suction filtration;
and step five, subpackaging the dried self-made hydrogel and the titanium metal bracket into a self-made glass grinding tool, placing the self-made glass grinding tool into a vacuum drying oven, performing gradient heating to obtain the gum dilator with the dry self-made hydrogel, performing gradient heating at the initial temperature of 80 ℃, maintaining for 24 hours, and finally heating at 120 ℃ for 15 minutes.
Wherein the specific process of adopting the metal bracket of the 3D printed gum dilator in the step (1) comprises the following steps,
a. carrying out CT scanning on the jaw bone to obtain DICOM data, and preprocessing the image;
b. the MIMICS software reconstructs a complete full-jaw bone three-dimensional model, stores the model in an STL format and performs virtual implantation of a defect area;
c. the method comprises the following steps of designing shapes of a bracket, a screw and a screw hole in Geomagic, and converting a model into an NURBS model;
d. completing the CAD design of the personalized bracket;
e. manufacturing a titanium bracket form suitable for a specific damaged part by a rapid forming technology;
example 3
A method for manufacturing a gingival dilator comprises the following steps,
(1) adopting 3D to print a titanium metal bracket of the gum dilator;
(2) and preparing the hydrogel: the preparation of the hydrogel comprises the following steps,
step one, distilling and purifying a monomer MMA and a monomer NVP; purifying an initiator AIBN by adopting a recrystallization method;
step two, uniformly mixing 120g of monomer MMA, 40g of monomer NVP and 0.16g of initiator AIBN;
adding 0.16g of conventional cross-linking agent AMA into a pipette and shaking up;
adding 0.016g of conventional cross-linking agent EGDM into a liquid transfer gun, shaking up, performing ultrasonic oscillation, and performing suction filtration;
and step five, subpackaging the dried self-made hydrogel and the titanium metal bracket into a self-made glass grinding tool, placing the self-made glass grinding tool into a vacuum drying oven, performing gradient heating to obtain the gum dilator with the dry self-made hydrogel, performing gradient heating at the initial temperature of 80 ℃, maintaining for 24 hours, and finally heating at 120 ℃ for 15 minutes.
Wherein the specific process of adopting the metal bracket of the 3D printed gum dilator in the step (1) comprises the following steps,
a. carrying out CT scanning on the jaw bone to obtain DICOM data, and preprocessing the image;
b. the MIMICS software reconstructs a complete full-jaw bone three-dimensional model, stores the model in an STL format and performs virtual implantation of a defect area;
c. the method comprises the following steps of designing shapes of a bracket, a screw and a screw hole in Geomagic, and converting a model into an NURBS model;
d. completing the CAD design of the personalized bracket;
e. manufacturing a titanium bracket form suitable for a specific damaged part by a rapid forming technology;
the monomers MMA and NVP, the cross-linking agents AMA and EGDM respectively contain a stabilizing agent sodium hydroxide (NaOH) or p-hydroxyanisole (MEHQ), and in order to obtain a purer compound, the components are purified before reaction to remove the stabilizing agent. The distillation purification can be carried out by utilizing the difference of boiling points of the reagent and the stabilizer. The newly purchased analytical purity grade (AR grade) has an MMA content of 99.0% and contains a stabilizer MEHQ at a concentration of 30ppm, which can be further purified by utilizing the difference in boiling points between MMA and MEHQ, wherein the boiling point of MMA is 100 ℃ and the boiling point of MEHQ is 243 ℃, and MMA containing no MEQH can be obtained by heating and distilling the reagent at a temperature between 100 ℃ and 243 ℃. The purity of NVP is 99%, the purity of the NVP contains 100ppm NaOH stabilizer, the purity of AMA and the purity of EGDM are both more than 98.0%, the purity of AMA and EGDM both contain stabilizer MEHQ, and the NVP needs to be purified before use. The same method can purify NVP monomer, AMA crosslinking agent and EGDM crosslinking agent. The initiator AIBN is purified by recrystallization because it is in the form of a solid powder.
The volume difference between the hydrogel prepared by the invention in a dry state and the hydrogel after water absorption is about 4-6 times, the diameter before and after expansion can be changed from 0.9cm to 1.3-1.5cm, the expansion degree of the volume can be further regulated, the mechanical strength can reach megapascal level after complete expansion, the mechanical strength of the hydrogel in the dry state is very ideal, the shape can be trimmed by a scalpel or scissors, as shown in figure 2-A,
the invention is obtained by bulk polymerization by taking NVP and MMA as monomers, AIBN as an initiator and AMA and EGDM as cross-linking agents. The polymerization reaction needs to be carried out by a certain process (polymerization method). This experiment uses AIBN as the initiator, which generates free radicals that provide the reaction initiation kinetic energy, i.e., chain initiation. Chain initiation is one of the keys to obtaining polymers, a key reaction to control the rate of polymerization and molecular weight. In general, the initiator is a compound which is easily decomposed into radicals, has a weak bond in structure, and has a dissociation energy of 100-170kJ/mol, which is much lower than 350kJ/mol of the C-C bond energy. The initiator is generally azo compound or peroxy compound, the initiator selected by the invention is Azobisisobutyronitrile (AIBN), which is the most common azo initiator, and the thermal decomposition reaction formula is as follows:
C(CH3)2(CN)N=NC(CH3)2(CN)→2C(CH3)2(CN)·+N2↑
AIBN is decomposed during heating to generate free radicals, and the free radicals react with double bonds on NVP and MMA, so that chain initiation is realized. The decomposition reaction is a first-order reaction, no induced decomposition is carried out, and only one free radical is generated, so that the method has certain advantages for polymerization dynamic research and is more common. When AIBN is used, because the AIBN is a solid substance, the AIBN must be fully mixed, and after mixing, a more ideal product can be obtained under the condition that the solid substance cannot be seen by naked eyes. The conventional radical polymerization includes four polymerization methods, i.e., bulk polymerization, solution polymerization, suspension polymerization and emulsion polymerization. The bulk polymerization is the polymerization of monomers with or without a small amount of initiator, belongs to a homogeneous system, the whole polymerization process is always kept homogeneous, the polymerization site is positioned in the bulk, the heat dissipation is not easy in the polymerization process, the polymer is pure, and the molecular weight distribution is wide. The hydrogel obtained by the invention is synthesized by bulk polymerization. The bulk polymerization system only consists of monomers and a small amount (or no) of initiator, the product is pure, the post-treatment is simple, and the method is a relatively economic polymerization method.
The free radical polymerization mechanism is formed by the series and parallel connection of monomers such as chain initiation, chain growth, chain termination and the like in a microscopic process of converting monomer molecules into macromolecules. Chain initiation is a reaction for forming monomer free radicals, generally divided into two steps, the first step is initiator decomposition, the activation energy of the initiator is increased after heat absorption, the activation energy is generally 105-150kJ/mol, and primary free radicals are formed, the reaction rate is lower, and the decomposition rate constant is only 10-4-10-6And s. The second step is exothermic reaction, low activation energy, exothermic reaction process, high reaction rate, and subsequent chain growth reaction. Chain propagation is the opening of pi bonds of olefinic molecules by monomeric radicals, and addition to form new radicals. The activity of the new free radical is unchanged, and the new free radical continues to be in linkage addition with the alkene monomer to generate a structural unit with more chain free radicals. Chain termination generally includes coupling termination and disproportionation termination, free radical activity is high, isolation is difficult, interaction is easy to terminate, chain termination and chain growth are a pair of competing reactions, generally, monomer concentration is 1-10mol/L far greater than free radical concentration (10 mol/L)-8±1mol/L), the overall rate of propagation of the reaction is much greater than the rate of termination, so that high polymers can be obtained, and chain termination is possible when this balance of monomer concentration and free radical concentration is changed.
FIG. 3-A shows fully swollen hydrogel and dry hydrogel with the naked eye. The self-made hydrogel after complete expansion is shown on the left side of fig. 2-a, which is clear and transparent, with regular shape and diameter of about 1.4cm, and without obvious bursting and defects. The right side of figure 2-A is the dry self-made hydrogel, which is seen to be regular in shape, about 0.9cm in diameter, uniform and transparent, and free of obvious defects. FIG. 2-B is an optical microscopic view of the dry hydrogel under an optical microscope of 40 times, showing that the hydrogel has a uniform surface, a complete and continuous structure and no obvious defects. FIG. 2-C shows the hydrogel after completely absorbing water by 40 times under an optical microscope, and the hydrogel contains a large amount of water therein, and the water can freely move in the hydrogel, and the hydrogel is uniform and transparent and has no structural defects. FIG. 2-D is a photograph of hydrogel after complete swelling under an optical microscope of 40 times and vacuum drying, showing that the hydrogel is in a three-dimensional network shape, is relatively uniformly interconnected, and has no obvious structural defects.
3-A, 3-B and 3-C are scanning electron micrographs of the dry hydrogel, and the hydrogel surface is uniform and dense under an electron microscope of 200 times; the surface of the hydrogel is uniform and compact under a microscope of 1000 times multiplied by x, and micropores are uniformly distributed; tens of nanometer micropores are distributed on the surface of the microscope with the magnification of 5000 times. FIGS. 3-D, 3-E, and 3-F are scanning electron micrographs of the hydrogel after complete expansion and vacuum freeze-drying, and the hydrogel has a uniformly distributed porous structure under an electron microscope of 200 times magnification, and the pores are connected to form a network; under an electron microscope multiplied by 1000 times, the hydrogel is uniformly distributed with a porous structure, all pores are connected into a solid net, and a plurality of small pores are distributed in the large pores and at the joints; under a microscope of 5000 times of x, the joints of the hydrogel are uniform in structure and free of defects.
Measurement of swelling Rate of hydrogel
12 dry hydrogels with the diameter of 9mm and the height of 6mm and without obvious defects are randomly numbered, placed on an electronic scale for weighing, then placed in ringer's solution and sealed, and the sealed test pieces are placed in constant-temperature water at the temperature of 37 +/-1 ℃. The hydrogel absorbs water to swell and increase weight. Samples were taken every 1 hour for 24 hours before the test piece, and the weight of the sample after swelling was measured after drying the surface moisture with filter paper, after which the weight was weighed every 12 hours and recorded. The ringer's solution is changed every day. The ratio of the volume of the hydrogel after swelling to the volume of the hydrogel in the dry state was taken as the swelling ratio. The swelling ratio of the hydrogel after swelling in ringer's solution for t time is denoted as Qt and is calculated according to the following formula:
Qt=Vt/V0*100%
in the formula Vt: the volume of the hydrogel after swelling in ringer's solution for t time; v0: volume of hydrogel in dry state.
Since the direct measurement of the hydrogel volume is liable to cause errors, the weight after water absorption obtained by the weighing method is converted into the volume after the increase of the t time by the following formula.
Vt=V0+(mt-m0)/ρWater (W)
V0=m0/ρ0
Where rhoWater (W):1.0g/cm3;m0The quality of the hydrogel in a dry state; rho0: the density of the dry hydrogel measured by a pycnometer is 1.2g/cm3. And calculating the expansion rate according to the formula, and drawing an expansion curve graph. FIGS. 4 and 6-A show the swelling rate of the hydrogel in 37. + -. 1 ℃ constant temperature ringer's solution over 24 h. FIGS. 5 and 6-B show the swelling rate of the hydrogel in 37. + -. 1 ℃ thermostated ringer's solution in 7 days.
The hydrogel swelled to 413.48% + -3.1% of the dry volume in 24h, slowly swelled to 489.89% + -3.7% of the dry volume at 3d, 500.36% + -4.1% of the dry volume at 5d, and swelled to 505.87% + -3.6% of the dry volume at 7 d. It can be seen that the hydrogel in the formula expands to 4 times of the dry volume within 24 hours, and then slowly expands to 5 times of the dry volume within the next 3 days, and the hydrogel is ideal for the expansion of the soft tissues of the jaw and face.
Determination of compressive Strength of hydrogel
10 cylindrical dry hydrogels with a diameter of 9mm and a height of 6mm and no obvious defects were randomly divided into A, B groups. And (3) placing the dry hydrogel into a closed container filled with ringer's solution, and then placing the container into a constant-temperature water bath at 37 +/-1 ℃, wherein the dry hydrogel absorbs water and expands. The ringer's solution is changed once a day. The hydrogel in group A is placed in an electronic universal material testing machine for upward compression strength test at the 2 nd after expansion. The hydrogel in group B was placed in an electronic universal material tester for up-flow compression strength test at 28d after swelling.
The electronic universal material testing machine is arranged in a related way:
1. a clamp: and (4) carrying out vacuum clamping.
2. Setting parameters of the electronic universal material testing machine: under original Chinese edition software, the testing machine is set to compress, the loading beam is loaded at 1mm/min and uniform speed, the pound force sensor is 1.0KN, the control channel is set as a position, and a safe position limit is set on the loading beam. The compression stage was adjusted as follows before the start of the test to ensure consistency in horizontal and vertical position.
3. Manufacturing and adjusting a compression platform: the compression platform diameter is 50mm, and the cylindricality pole is reserved to the bottom and is linked to each other with the testing machine anchor clamps. To ensure that the compression platform is level, a level is placed on the compression platform to ensure that the platform is parallel to the horizontal. In order to ensure that the upper and lower compression platforms are consistent in the vertical direction, before a compression experiment, a compression stroke is simulated, the upper and lower compression platforms are adjusted to be in surface-to-surface contact and completely overlapped, and then the experiment is started. The compression platform is tightened by a vacuum clamp, and the platform is adjusted rigidly when being adjusted.
4. Compression test operation: and (3) clamping the upper and lower compression platforms by a vacuum clamp, recording the diameter of the hydrogel by a digital vernier caliper after ensuring that the horizontal and vertical directions are correct, and placing the hydrogel in the center of the experiment platform below. And manually and slowly moving the loading beam to clear the displacement value of the test system and the force value of the loading beam when the upper loading platform is just close to the hydrogel so as to clear test errors caused by the tester, the loading platform and the like. The click start test is carried out, the mechanical data collected by the loading beam is increased along with the increase of displacement, the force value of the loading beam is suddenly reduced due to the rupture of hydrogel at a certain moment, and the peak value F, unit: and N is added.
And calculating the compression strength of each test piece by using the P ═ F/S.
Wherein, P is the compression strength (compressive strength) of the hydrogel, MPa;
f ═ peak stress at hydrogel cleavage, N;
S=πr2cylinder area of cylindrical hydrogel, mm2。
The compressive strength of the A, B set of hydrogels was calculated by the formula P ═ F/S and is shown in fig. 7 and 8.
The mechanical test time points are selected as the 2 nd and 28 th after expansion, and the mechanical properties of the hydrogel at two key time nodes are mainly better understood. The hydrogel was in a relatively fast swelling phase 2d before swelling, so its mechanical properties were tested. The mechanical properties were tested after 28d expansion to simulate the mechanical properties of the hydrogel after implantation in vivo for a long time. The mechanical properties before expansion are also important, but obviously, the mechanical properties of the hydrogel before expansion are ideal, and the hydrogel is hardly likely to be cracked due to compression under the conventional conditions, so that the mechanical properties before expansion are not tested.
When the compression strength testing is carried out, along with the uniform-speed loading of the loading head, the force value curve is always upward, when the hydrogel cracks, the force value curve is rapidly downward, the mechanical peak value is recorded as the maximum compression force, the force value can be clearly identified in a force value-displacement graph, and the characteristic is strong. The hydrogel is split only by force and not completely broken, and still has integrity. The performance provides a certain guarantee for the safety of clinical use of the material, and even if the hydrogel is impacted or cracked by other accidents after being implanted into the body, the hydrogel can still be completely taken out and is not easy to remain in the body.
After the self-made hydrogel in the group A is subjected to water absorption and expansion for 2 days, the compressive strength is still as high as 5.23 +/-0.41 MPa, the mechanical property is very ideal, and even after the self-made hydrogel is expanded for 28 days, the compressive strength is 1.79 +/-0.20 MPa, so that the clinical requirements can be completely met. Dental restorative materials often have bond strengths greater than 0.44MPa (4.5 kg/cm)2) The material has higher strength than the bonding strength of the dental prosthetic material and more ideal mechanical property; the invention selects two crosslinking agents of AMA and EGDM to be used simultaneously, and the addition of the crosslinking agents according to the proportion of 0.1 wt% and 0.01 wt% respectively can obtain more ideal mechanical properties.
Hydrogel energy spectroscopy
3 complete and defect-free self-made hydrogels are taken, are cylindrical, have the diameter of 9mm and the height of 6mm, and are respectively numbered as sample 1, sample 2 and sample 3. Sample 1 is expanded for 1d in physiological saline at 37 +/-1 ℃, then frozen in a liquid nitrogen biological container for 24h, the dental osteotome is rapidly split, and then placed in a freezing vacuum drier for full drying for 24h (drier parameters: cold well-65 ℃ and vacuum degree 0Pa), and hydrogel with a smooth surface and a diameter of about 0.5cm is taken as an analysis sample. Fixing a sample on a base of a scanning electron microscope by using conductive adhesive, shearing the conductive adhesive into a long arrow shape, pointing to an analysis part, placing the sample on the surface of an ion sputtering instrument for spraying gold, placing the sample in an SEM observation bin after spraying the gold, performing energy spectrum analysis under the condition of a 15kV pressurized electric field after vacuumizing, and analyzing the components and the content proportion of the hydrogel. And a sample 2 is self-made dry hydrogel, is frozen and stored in liquid nitrogen for 24 hours and then is split, is fixed on a base of a scanning electron microscope by conductive adhesive, is cut into a long arrow shape, points to an analysis part, is sprayed with gold, and is subjected to energy spectrum analysis. And (3) swelling the sample in physiological saline at 37 +/-1 ℃ for 7d, freezing and storing the sample in liquid nitrogen for 24h, splitting the sample, adhering conductive adhesive, spraying gold, and performing energy spectrum analysis. When the three samples are subjected to energy spectrum analysis, the parameters of the spectrum analyzers are consistent.
The result shows that the main elements of the hydrogel are carbon and oxygen, the chlorine and sodium elements in the hydrogel are a small amount of residues in the hydrogel after being contacted with normal saline, and the gold element is the result after being treated by spraying gold because the hydrogel is not conductive. The spectral analysis patterns of samples 1, 2 and 3 are shown in fig. 9, 10 and 11, respectively.
When the hydrogel is subjected to energy spectrum analysis, a 15kV pressurizing electric field is selected, mainly because the relatively low pressurizing electric field can increase the X-ray intensity of light elements, improve the spatial resolution and reduce the damage to a sample. While for some metallic elements or trace elements it is advisable to choose a high applied electric field. The energy spectrum analysis result shows that the main elements of the hydrogel are carbon and oxygen, the weight ratio and the atomic weight ratio of the carbon to the oxygen are both about 90 percent, and the rest components are mainly sodium chloride which is the component of normal saline and gold which needs to be sprayed due to electric conduction. The hydrogel is relatively simple in elemental composition and is derived primarily from the polymerization product of the monomers Methyl Methacrylate (MMA) and N-vinyl pyrrolidone (NVP). But no hydrogen and nitrogen were detected as a result of the energy spectrum. The NVP monomer contains nitrogen element, and the Azodiisobutyronitrile (AIBN) initiator also contains nitrogen element, but is not detected, and the reason for analyzing the NVP monomer is probably that the NVP monomer content is extremely low, and the detection sensitivity to the nitrogen element after gold spraying is low. In addition, AIBN (azobisisobutyronitrile) as an initiator was added in an amount of only 0.1% by weight, and it generated nitrogen gas while generating radicals to initiate bulk polymerization, and the gas could not be detected by an energy spectrum analyzer. Therefore, nitrogen-containing substances are involved in the reaction before the reaction, but nitrogen is not detected in the energy spectrum analysis because of the low content and partial generation of nitrogen. The reason why hydrogen is not detected is that the spectrum analyzer does not have a function of detecting hydrogen, and the spectrum analyzer operates on the principle that electrons make transitions to release characteristic energy Δ E, but hydrogen only has one electron shell and does not make transitions of outer electrons, and therefore, a characteristic signal cannot be generated, and the same element includes helium.
In the three samples which are sent for inspection, the element weight ratio and the atom content ratio are relatively close, which indicates that the components of the detection areas of the three samples are relatively consistent, and also indicates that the hydrogel is very uniform, certain elements are not accumulated in certain places, the agglomeration or accumulation of certain elements is not generated, the components are well dispersed, and the phenomenon is consistent with that observed under an optical microscope and an SEM.
Evaluation of partial biological Properties of hydrogels
For human body implant materials, strict admission requirements are met both internationally and domestically, and the biological safety of the human body implant materials must be strictly demonstrated. International ISO10993 and domestic Y/T0127.8-2001 have made clear requirements on the biological safety of medical materials. The biological material must not cause any negative effects on the patient, including short-term (acute) and long-term (chronic) negative effects on the human body, such as cytotoxicity, genotoxicity, systemic toxicity, sub-chronic toxicity, sensitization, irritation or intradermal response, implant response, hemocompatibility, mutagenic effect, etc. For this reason, medical devices should generally be subjected to biosafety assessments and biocompatibility tests to assess the interaction between the device and patient tissue, cells, or bodily fluids.
The soft tissue expander has achieved good clinical effect after decades of improvement, but is easy to cause complications such as infection, expander rupture, tissue necrosis and mechanical extrusion after operation, and the expander is single in shape, can not be freely modified, and can not adapt to the complicated shape of the maxillofacial region. The subject is to prepare a novel self-expanding hydrogel for expanding soft tissues of maxillofacial region, and the early in vitro experiments show that the self-expanding hydrogel has controllable expansion speed and good mechanical strength after being completely expanded. According to the invention, after the self-made self-expanding hydrogel is implanted into the jaw face of an SD rat, the healing conditions of 1w, 2w and 4w incisions after operation are observed: the presence or absence of obvious symptoms of inflammation, allergy, necrosis, wound dehiscence, implant exposure and the like and the presence or absence of systemic toxic reactions in rats were evaluated histologically at 1w, 2w and 4w after surgery by hematoxylin-eosin (HE) staining to further confirm the biosafety and ability to dilate soft tissues in vivo.
20 healthy and clean SD rats (250 +/-25) g with the age of 50-60 days are selected and provided by the animal laboratory department of medical colleges of Nanchang university. All rats were fed with normal feed, were fed freely with water, and were randomly divided into 4 groups of 5 animals each, after 1w of adaptive feeding: the group A is a normal control group, the group B is an implanted hydrogel 1w expansion group, the group C is an implanted hydrogel 2w expansion group, and the group D is an implanted hydrogel 4w expansion group.
Placing the required self-expanding cylindrical dry hydrogel with the diameter of 9mm and the height of 3mm in a full-automatic sterilizer with the temperature of 121 ℃ and the pressure of 0.11MPa, and sterilizing for 15min for later use. Randomly selected 5 rats as normal control group (group a) without any treatment; the rest 15 rats are respectively anesthetized by intraperitoneal injection with 10% chloral hydrate solution (2mL/kg), when the rats are in a deep anesthesia state, an incision of about 15mm is made after depilation and sterilization of the central area of the two ear connecting line of the rats, the incision reaches the periosteum deeply and blunt separation is carried out, and the periosteum is prevented from being damaged as much as possible in the separation process. Placing sterilized cylindrical dry hydrogel into the incision, placing the implanted hydrogel edge 4-5mm away from the incision, intermittently suturing the incision, and coating appropriate amount of erythromycin eye ointment on the incision to protect wound surface. All rats were not re-administered any antibiotics after surgery. These 15 rats were randomly divided into: hydrogel was implanted for 1 week (group B), 2 weeks (group C), and 4 weeks (group D).
Rats were observed for the presence of systemic toxicity responses according to the acute systemic toxicity grading (Gradef systematic toxicityTest) standard (ISO10993-11, 2006) (FIG. 12). Meanwhile, the healing conditions of the rat incision are observed, such as no obvious inflammation, allergy, necrosis, incision cracking, hydrogel exposure and the like. The rats of group B, group C and group D were sacrificed at 1w, 2w and 4w after the operation, and the self-swelling hydrogel and the surrounding tissues implanted in the jaw face of the rats were excised as a whole while observing whether the self-swelling hydrogel was intact and its relationship with the surrounding tissues. The adjacent tissues and hydrogels were then fixed with 10% formalin (hydrogel from group B was completely separated from the tissue, hydrogel could not be fixed in the pathological section), and histological evaluation was performed by observing the specimens under an optical microscope after HE staining. The skull of the corresponding position of the hydrogel of the rats in the A group and the D group is cut by a dental planter, fixed by 10 percent formalin, decalcified, sliced and stained, and then pathologically observed.
All experimental rats implanted with hydrogels did not show one systemic toxicity response as observed by acute systemic toxicity grading criteria. All rat wounds healed well without infection, allergy, necrosis, wound dehiscence and hydrogel exposure. All hairs covered above the implant grow normally, the hydrogel form in the body of the implanted rat is kept good, the self-expanding hydrogel is not cracked in the process of taking out the implant, the whole body can be taken out, and no residue exists in the surrounding tissues.
After rats of the blank control group (group a) and the hydrogel were implanted into groups 1w (group B), 2w (group C) and 4w (group D), gross specimens were visually observed, fixed with 10% formalin, stained with hematoxylin-eosin (HE) by the same pathologist, and then observed and analyzed under an olympus BX-41 optical microscope.
Fig. 13A and 13E are a meat eye diagram and a microscopic (100 times) diagram of normal soft tissue of the jaw face of group a SD rats, and the normal soft tissue of the jaw face is visible in the general specimen. The stratified squamous epithelium, hair follicle, connective tissue layer are visible under the mirror.
FIGS. 13B and 13F are a meat eye diagram and a microscopic image (100 times) of soft tissues of the jaw face of the SD rat in the group B, wherein the soft tissues of the general specimen are slightly thickened and swollen compared with the control group, no obvious fiber envelope is generated, the hydrogel is completely separated from the soft tissues, is not adhered and wrapped, is intact and has no defect and no fragmentation, and has the diameter of about 1.4cm and the height of about 0.5 cm. Under the microscope, a large amount of inflammatory exudates, a large amount of lymphocyte infiltration and a large amount of new small blood vessels are formed near hydrogel.
Fig. 13C and fig. 13G are a photomicrograph and a photomicrograph (x 100 times) of soft tissue of the jaw face of SD rats in group C, showing that the thickness of the soft tissue of the gross specimen is substantially the same as that of the control group, without obvious swelling and thickening, a thin layer of envelope is arranged at the contact part with the hydrogel, the envelope is uniform, continuous and complete, the hydrogel is completely wrapped by the envelope, the hydrogel is complete and free of defects and fragmentation, the diameter is about 1.4cm, and the height is about 0.5 cm. A thin fiber envelope is formed around the hydrogel under the microscope, hydrogel is occasionally seen in the envelope, a small amount of inflammatory tissues and a small amount of new blood vessels are occasionally seen in soft tissues.
Fig. 13D and 13H are a photomicrograph and a photomicrograph (x 100 times) of soft tissue of the jaw face of SD rats in group D, showing that the thickness of the soft tissue of the gross specimen is substantially the same as that of the control group, without swelling and thickening, and an envelope is formed at the contact position with the hydrogel, the envelope is uniform, continuous, complete and relatively dense, the hydrogel is completely wrapped by the envelope, the hydrogel is complete and free of defects and fragmentation, the diameter is about 1.4cm, and the height is about 0.5 cm. A layer of fiber envelope is arranged around the hydrogel under a microscope, the envelope is continuous and complete, hydrogel is occasionally seen in the envelope, inflammatory cells are not seen, and a small amount of new blood vessels are occasionally seen.
Fig. 13-A and 13-B are pathological section images of rat skull in control group and D group, and no bone resorption and no active osteoclast and osteoblast were observed in both groups. Inflammatory cells are not seen on the scalp side and the brain side of the skull.
The experimental results suggest that no acute systemic toxicity is found in four groups of SD rats, and the acute systemic toxicity is normal in comparison with the ISO10993 acute systemic toxicity classification standard (figure 12), which proves that the self-made hydrogel may not generate acute toxicity reaction. The wounds of all experimental groups are well healed, and the abnormal conditions such as allergy, rejection, necrosis and the like are not generated, and the conditions such as skin necrosis, implant prolapse and the like caused by over expansion of the implant are not generated. The main components of the self-expanding hydrogel researched and developed by the invention are NVP and MMA, the synthesized product is a three-dimensional reticular polymer compound, the biological materials of the components are widely applied to the field of medicine, no toxic or side effect is generated on animals, and all experimental rats observed in the whole experimental process have good survival after operation, normal reaction and normal hair color and luster, and no acute toxic reaction is generated.
The experiment of implanting the self-swelling hydrogel into the maxillofacial part of the rat shows that the self-swelling hydrogel implanted into the maxillofacial part of the rat is easy to be completely taken out in the taking-out process when the self-swelling hydrogel is respectively 1w, 2w and 4w after operation, and the conditions of hydrogel fragmentation, adhesion and the like do not occur, which indicates that the strength of the self-made hydrogel is good, and the pressure of soft tissues and the impact force of the rat during movement are not enough to damage the integrity of the hydrogel. The early in vitro experimental study also finds that the expansion rate of the self-made hydrogel within 7 days is 5.05 +/-0.04 times, and proves that the 5.05 times of expansion does not cause the necrosis of the soft tissues of the maxillofacial region of the SD rat. The early in vitro compression strength indicates that the compression strength of the hydrogel after complete expansion can reach 1.79 +/-0.20 MPa, and the animal experiments find that the hydrogel in all rats keeps the shape intact, so that the strength of the hydrogel is good, and obvious mechanical property change caused by the in vivo environment and expansion time can be avoided.
The experiment was divided into four groups: normal control group (group a), hydrogel-implanted 1w group (group B), hydrogel-implanted 2w group (group C), and hydrogel-implanted 4w group (group D). The local tissue reaction of the biomaterial implant in vivo is similar to the general wound healing process and mainly comprises an inflammatory phase and a repair phase, wherein the inflammatory reaction phase is 3-4d, a large number of inflammatory cells can be seen after HE staining, the inflammatory cells are represented by large and bright blue nuclei and large nucleus-cytoplasm ratio, the cytoplasm is in different pink colors, and eosinophilic granules in the biomaterial implant are in bright red with strong light reflection, which is basically consistent with the phenomenon observed in the group B and probably mainly caused by surgical wounds. The number of inflammatory cells was gradually reduced to regress after HE staining during the repair phase, which was closer to the phenomenon observed in group C. After the biological material is implanted into the body, the inflammation period and the repair period of the biological material are correspondingly prolonged as a continuous expansion stimulus. Meanwhile, as a layer of biological fiber coating can be seen around the biological material after the biological material is implanted in a body for a period of time, the fiber coating has two main functions: one is to prevent the implant from spreading around the tissue; secondly, the formation of the fiber coating can prevent the implant from further contacting with the surrounding tissues, thereby avoiding the cells of the surrounding tissues from being continuously activated. Research shows that the fiber coating begins to form at about 1w after the biological material is implanted into a body, the fiber coating gradually matures at 2w, and the thickness of the fiber coating is thicker than before at 4 w. Therefore, in the experiment, the observation group is set to be 1w, 2w and 4w after the self-expanding hydrogel is implanted into the maxillofacial region of a rat, the self-expanding hydrogel is taken out in corresponding time periods respectively, and the self-expanding hydrogel is observed by HE staining. However, no significant fibro-capsule formation was observed at 1w postoperatively in this experiment, which may be due to incomplete loose connective tissue at this stage. The pathological sections in the group D simultaneously indicate that the hydrogel is not obviously different from the corresponding expanded soft tissue and the non-expanded soft tissue in morphology, which indicates that the soft tissue obtained after the expansion is possibly completely consistent with the healthy tissue. No active osteoclasts were observed, nor was significant bone resorption seen in pathological sections of the skull of rats in groups a and D, suggesting that home-made hydrogels may not cause bone resorption during swelling.
In the process of preparing pathological sections, soft tissues and hydrogel taken out of the rat body are fixed with formalin, and then proteins of tissues and cells are denatured and solidified, so that dead cells are prevented from autolysis or bacterial decomposition, but the volume of hydrogel is also reduced. After dehydration by low-concentration to high-concentration alcohol, the water in the tissue block is gradually removed, and simultaneously, the water in the hydrogel is also removed, and the hydrogel is easy to be separated from the tissue at the moment, and is always completely separated from the tissue during paraffin embedding. To observe the tissue and hydrogel in the same section, care is taken during dehydration and embedding, as is to ensure the integrity of the envelope, or if necessary, to backfill the hydrogel into the envelope. The embedded wax block is fixed on a slicer and cut into 6 mu m slices, the cut slices are often folded, and the hydrogel is easy to fall off, so that an experienced technician needs to be careful to obtain the slices containing the hydrogel and the soft tissues.
In conclusion, the experimental result of implanting the self-expanding hydrogel into the maxillofacial region of the SD rat shows that the self-expanding hydrogel has good biocompatibility, has an expansion effect on the maxillofacial soft tissues and also has good mechanical strength after complete expansion.
Preliminary evaluation of hydrogels by imaging
After the self-made hydrogel is implanted into a body, if the expansion process of the self-made hydrogel needs to be observed and the expansion effect needs to be evaluated or the self-made hydrogel needs to be taken out under certain special conditions, the self-made hydrogel is usually evaluated and analyzed by means of imaging equipment, so that the experiment adopts several imaging methods which are most commonly used clinically to preliminarily evaluate the imaging condition of the self-made hydrogel in an SD rat body. The invention adopts color Doppler ultrasound, spiral CT and Magnetic Resonance Imaging (MRI) to perform preliminary evaluation on SD rats implanted with self-made hydrogel 1w in the maxillofacial region.
Placing the required self-made self-expanding cylindrical dry hydrogel with the height of 3mm and the diameter of 9mm in a full-automatic sterilizer with the temperature of 121 ℃ and the pressure of 0.11MPa, and sterilizing for 15min for later use. Selecting 3 rats, carrying out intraperitoneal injection anesthesia by using 10% chloral hydrate solution (2mL/kg), and making an incision of about 15mm after unhairing and disinfecting in the central area of the two ear connecting line of the rats when the rats are in a deep anesthesia state, wherein the incision reaches the periosteum deeply and is subjected to blunt separation, and the periosteum is prevented from being damaged as much as possible in the separation process. Placing the sterilized cylindrical dry hydrogel into the incision, placing the implanted hydrogel edge 4-5mm away from the incision, intermittently suturing the incision, and applying appropriate amount of erythromycin eye ointment to the incision after operation. All rats were not re-administered any antibiotics after surgery. After anesthesia of SD rats by 10% chloral hydrate at 1w after operation, primary evaluation is carried out on hydrogel imaging in vivo by color Doppler ultrasound, spiral CT and MRI, whether the self-made hydrogel is complete and broken or not is observed, whether the hydrogel and surrounding tissues have different image values or not and whether the boundaries with adjacent tissues are clear or not is observed, and the diameter and the height of the hydrogel are measured.
Color doppler ultrasound observations: under 10% chloral hydrate anesthesia, the SD rat is uniformly coated with medical ultrasonic couplant on the maxillofacial region, and the boundary, blood flow and size of the SD rat are observed by a color Doppler ultrasonic instrument. Ultrasonic prompting: the self-made hydrogel is in a dark area, has no blood flow signal, has a clear boundary, is cylindrical in a measurement dark area, has the diameter of about 1.4cm and the height of about 0.5cm, and has no obvious abnormality in the soft tissues of the maxillofacial region (fig. 14A). Helical CT observations: SD rats were examined under deep anesthesia with 10% chloral hydrate, CT suggesting: the CT imaging of the expanded hydrogel is clearer, the HU value of the expanded hydrogel is different from that of surrounding tissues, a clearer limit is provided, the hydrogel is in a regular column shape, the diameter is about 1.4cm, the height is about 0.4cm, the soft tissues of the maxillofacial region are not obviously abnormal, and bone absorption at the corresponding position of a jaw bone is not seen (fig. 14B). Magnetic resonance observations: SD rats were examined under deep anesthesia with 10% chloral hydrate for MRI, which suggested: the image of the self-swelling hydrogel was very bright and had a clear boundary with the surrounding tissue, and the hydrogel was measured to be in a regular cylindrical shape with a diameter of about 1.4cm and a height of about 0.5cm, and no obvious abnormality was observed in the soft tissue of the maxillofacial region (fig. 14C).
The color ultrasound in animal experiments suggests that the self-made hydrogel has dark areas, which is consistent with the principle of ultrasonic imaging. The dark areas generally represent fluid areas such as blood, amniotic fluid, fluid accumulation, bile or urine, which is associated with the hydrogel absorbing a large amount of body fluid after being implanted in the body at 1w [89 ]. Ultrasound has significant image differences between fluid and parenchymal tissue, and the boundary between hydrogel and surrounding tissue is quite clear in animals, also because hydrogel absorbs large amounts of fluid. The ultrasound indicates that no blood flow signal exists in the hydrogel, which indicates that no new blood vessel enters the hydrogel, and the phenomenon is consistent with the phenomenon that a layer of envelope is formed around the hydrogel in the later period, and no new blood vessel exists in the hydrogel in a pathological section.
Animal experiment CT result suggestion self-control aquogel formation of image is comparatively clear, and is different with tissue HU value on every side, has comparatively clear limit, explains can form images through CT to the aquogel after absorbing water, and aquogel has certain resistance to penetrate nature, and aquogel does not also produce the artifact simultaneously.
The animal experiment MRI result indicates that the self-made hydrogel is highlighted in imaging, and the boundary between the self-made hydrogel and the surrounding tissues can be clearly observed on both the T1 weighted phase and the T2 weighted phase, so that the hydrogel is mainly absorbed by liquid and is expanded in an animal body.
The titanium metal support comprises a fixing piece 2, a mounting piece 7, a connecting piece 8 and a mounting seat 3, wherein the fixing piece 2 is connected with the mounting piece 7 through the connecting piece 8, a movable groove 5 is formed in the mounting piece 7, the mounting seat is arranged in the movable groove, an accommodating hole 6 is formed in the upper end face of the mounting seat 3, and the hydrogel is synthesized in the accommodating hole 6; a plurality of screw holes 1 are uniformly distributed on the fixing piece 2; a plurality of reinforcing rods 4 are arranged in the accommodating hole 6.
Preparing a titanium stent: according to the structural parameters after research and optimization, the CAD modeling of three-dimensional mesh stent materials with various different parameters and the personalized restoration of the animal mandible defect model is completed, and the materials are introduced into an ArcamQ10 type electron beam layer-by-layer melting metal forming (EBM) experimental facility (Swedish Dicam Co., Ltd.) after rapid prototyping data processing. The powder raw material is adopted to prepare the personalized titanium stent by molding Ti-6Al-4V medical treatment (surgical implantation) titanium alloy powder particles provided by the company Arcam in Sweden, wherein the titanium alloy powder particles are approximately spherical and have the average particle size of about 80 mu m.
The foregoing is merely illustrative of the preferred embodiments of the present invention and is not to be construed as limiting the claims. The present invention is not limited to the above embodiments, and the specific structure thereof is allowed to vary. All changes which come within the scope of the invention as defined by the independent claims are intended to be embraced therein.
Claims (3)
1. A manufacturing method of a gum dilator is characterized in that: the method comprises the following steps of,
(1) adopting 3D to print a titanium metal bracket of the gum dilator;
(2) and preparing the hydrogel: the preparation of the hydrogel comprises the following steps,
step one, purifying required reagents according to classes, wherein liquid reagents are purified by distillation, and solid reagents are purified by a recrystallization method;
step two, uniformly mixing monomer MMA, monomer NVP and initiator AIBN, wherein the mass ratio of the monomer MMA to the monomer NVP is 3:1, and the mass of the initiator AIBN is 0.1 percent of the total weight of the monomer MMA and the monomer NVP;
adding a conventional cross-linking agent AMA with the mass being 0.1 percent of the total weight of the monomer MMA and the monomer NVP into the pipette, and shaking up;
adding a conventional cross-linking agent EGDM with the mass being 0.01 percent of the total weight of the monomer MMA and the monomer NVP into a pipette, shaking up, performing ultrasonic oscillation, and performing suction filtration;
and fifthly, subpackaging the dried gingiva dilator and the titanium metal bracket together into a self-made glass grinding tool, putting the self-made glass grinding tool into a vacuum drying oven, and heating the self-made glass grinding tool by gradient heating to obtain the gingiva dilator with the dry self-made hydrogel.
2. The method for manufacturing a gingival dilator according to claim 1, wherein: the specific process of adopting the metal bracket of the 3D printed gum dilator in the step (1) comprises the following steps,
a. carrying out CT scanning on the jaw bone to obtain DICOM data, and preprocessing the image;
b. the MIMICS software reconstructs a complete full-jaw bone three-dimensional model, stores the model in an STL format and performs virtual implantation of a defect area;
c. the method comprises the following steps of designing shapes of a bracket, a screw and a screw hole in Geomagic, and converting a model into an NURBS model;
d. completing the CAD design of the personalized bracket;
e. manufacturing a titanium bracket form suitable for a specific damaged part by a rapid forming technology;
3. the method for manufacturing a gingival dilator according to claim 1, wherein: in the fifth step, the initial temperature of the gradient temperature rise heating is 80 ℃, the temperature is maintained for 24 hours, and finally the heating is carried out for 15min at 120 ℃.
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CN106965291A (en) * | 2017-04-07 | 2017-07-21 | 南京先临三维科技有限公司 | A kind of gel injection-moulding 3D printing preparation method of gradient ceramic |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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CN106965291A (en) * | 2017-04-07 | 2017-07-21 | 南京先临三维科技有限公司 | A kind of gel injection-moulding 3D printing preparation method of gradient ceramic |
WO2019160759A1 (en) * | 2018-02-13 | 2019-08-22 | Zegarelli Peter John | Methods of making an oral appliance |
Non-Patent Citations (3)
Title |
---|
3D生物打印兔肺成纤维细胞水凝胶结构体片段;罗涛;《基础医学与临床》;20180930;全文 * |
β折叠型自组装短肽水凝胶特性及在神经组织工程中的应用前景;卫巍;《中国组织工程研究》;20180408;全文 * |
自体膨胀水凝胶体内膨胀率及生物相容性的实验研究;李平平;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20130215;全文 * |
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