CN109999225A - A kind of bone renovating material and preparation method thereof - Google Patents

A kind of bone renovating material and preparation method thereof Download PDF

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Publication number
CN109999225A
CN109999225A CN201910375018.2A CN201910375018A CN109999225A CN 109999225 A CN109999225 A CN 109999225A CN 201910375018 A CN201910375018 A CN 201910375018A CN 109999225 A CN109999225 A CN 109999225A
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bone
renovating material
bone renovating
material according
tissue
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CN109999225B (en
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赵应征
鲁翠涛
徐荷林
姚情
杨外庚
陈睿
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Wenzhou Medical University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/20Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3633Extracellular matrix [ECM]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56Porous materials, e.g. foams or sponges
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/02Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Oral & Maxillofacial Surgery (AREA)
  • Engineering & Computer Science (AREA)
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  • Urology & Nephrology (AREA)
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Abstract

The present invention provides a kind of bone renovating material, its main component includes that adipose tissue goes cellular matrix, palmityl tetrapeptide -7, fibroin albumen, heparin poloxamer and the indoles mountain valley with clumps of trees and bamboo green, the bone renovating material passes through 785nm near infrared light, quickly solidify to form the three dimensional elasticity grid structure being adapted with bone defect tissue, its performance indexes is excellent, biocompatibility is good, with good bone wound repair, the replacement graft that can be used as bone tissue, the orthotopic transplantation reparation for bone tissue wound.

Description

A kind of bone renovating material and preparation method thereof
Technical field
The present invention relates to medicine Bone Defect Repari fields, and in particular to a kind of rapid shaping, highly effective and safe bone renovating material and Preparation method.
Background technique
In recent years because caused by the reasons such as traffic accident, disaster bone wound phenomenon it is more and more, and bone wound repair process it is complicated and It is very long, seriously affect the movable function and quality of life of people.
Bone renovating material is the key that realize bone wound treatment.Bone renovating material has at present: (1) autologous bone: referring to from body The bone at a certain position shift to another place, but be only applicable to the bone wound treatment of local small area.Due to the area Qu Gu of body Optional position is limited, while complication easily occurs, and generates new obstacle for autologous bone transplanting.(2) homogeneous allogenic bone: allograph bone is come Source, with different hereditary features, easily causes to be immunoreacted far more than autologous bone, but due to being interindividual transplanting, Also cross-infection easily occurs.(3) artificial bone: artificial bone refers to that the people's bone substitute or fracture of manually material manufacture are solid Determine material.There is many defects for artificial bone at present, and such as on the high side, safety has much room for improvement, and lack preferable adherency It acts on curable type, is easily lost in site of injury.In addition, the above bone renovating material does not have the ability of rapid shaping, it can not be in bone The rapid curing molding in tissue trauma position realizes the quick healing at bone defect position.
Ideal bone renovating material should meet claimed below: 1. can quickly solidify to form and bone in bone tissue wound site The adaptable three dimensional elasticity grid structure of defective tissue, realizes the quick healing at bone defect position.2. good biocompatibility And Bioabsorbable.3. there are the mechanical characteristics such as good elastic strength, wear-resisting property, it can be with the mechanics of tissue implant site It is required that matching.It is suitble to cell adherence, hyperplasia and the surface chemistry of differentiation 4. having, is conducive to osteoblast attachment, is Oesteoblast growth provides immediate extracellular microenvironment.5. preparation flow is simple and easy, the bone renovating material prepared Product is easy long-term preservation.
Clinically it cannot all meet all conditions above simultaneously for the material of Bone Defect Repari at present, especially shortcoming is in bone group The ability of the rapid curing molding of wound site is knitted, therefore forms technical bottleneck.
Summary of the invention
In order to overcome the bottleneck of the prior art, the purpose of the present invention is to provide one kind with fast in bone tissue wound site The ability of fast curing molding and meet the bone renovating material that ideal bone renovating material is required.The bone renovating material plays each The collaboration advantage of kind component, the orthotopic transplantation reparation for bone tissue wound.
By many experiments, present invention applicant filters out a kind of bone renovating material for meeting desirable, the Bone Defect Repari Material main component includes that adipose tissue removes cellular matrix, palmityl tetrapeptide -7, fibroin albumen, heparin poloxamer and the indoles mountain valley with clumps of trees and bamboo Green, which passes through 785nm near infrared light, quickly solidifies to form the three dimensional elasticity being adapted with bone defect tissue Grid structure.
The quality proportioning of each component in above-mentioned bone renovating material are as follows: adipose tissue removes 1~4 part of cellular matrix, palmityl 0.1~0.5 part of tetrapeptide -7,2~10 parts of fibroin albumen, 2~8 parts of heparin poloxamer, green 0.01~0.5 part of the indoles mountain valley with clumps of trees and bamboo.
The quality proportioning of each component is preferred in above-mentioned bone renovating material are as follows: adipose tissue removes 2 parts of cellular matrix, palmityl 0.2 part of tetrapeptide -7,5 parts of fibroin albumen, 4 parts of heparin poloxamer, green 0.05 part of the indoles mountain valley with clumps of trees and bamboo.
Chondroitin sulfate is further added in above-mentioned bone renovating material, hyaluronic acid, collagen, promotes bone growth Bioactie agent is one or more of.
Hydroxyapatite, calcium sulfate, calcium citrate, calcium phosphate, ocean life are further added in above-mentioned bone renovating material The bone shell and its extract of object.
A kind of preparation method of above-mentioned bone renovating material gelling agent, goes cellular matrix to crush above-mentioned adipose tissue, It is dissolved in 30ml distilled water solution, the solution that 40ml includes fibroin albumen, palmityl tetrapeptide -7 is added, mixes, is eventually adding 10ml indoles mountain valley with clumps of trees and bamboo green solution mixes, adds distilled water to final volume 100ml, form the gelling agent of uniform bone renovating material.
Chondroitin sulfate is further added in above-mentioned bone renovating material preparation process, hyaluronic acid, collagen, promotes bone group The bioactie agent for knitting growth is one or more of.
Hydroxyapatite, calcium sulfate, calcium citrate, phosphoric acid is further added in above-mentioned bone renovating material preparation process Calcium, marine organisms bone shell and its extract.
The common antioxidant of pharmacy, wetting agent, solubilizer, pH are further added in above-mentioned bone renovating material preparation process Regulator.
Above-mentioned bone renovating material is used for the orthotopic transplantation reparation of bone tissue wound.
Bone renovating material of the invention has following advantages: 1. solidifying rapidly in bone tissue wound site, is formed and lacked with bone The adaptable three dimensional elasticity grid structure of tissue is damaged, realizes the quick healing at bone defect position.2. good biocompatibility and Bioabsorbable.3. having the mechanical characteristics such as good elastic strength, wear-resisting property, can be wanted with the mechanics of tissue implant site It asks and matches.Be suitble to cell adherence, hyperplasia and the surface chemistry of differentiation 4. having, be conducive to osteoblast attachment, at Bone cell growth provides immediate extracellular microenvironment.5. preparation flow is simple and easy, the bone renovating material prepared is produced Product are easy long-term preservation.
Specific embodiment
The specific embodiment of the invention is discussed in detail below.It should be noted that technology described in following embodiments is special The combination of sign or technical characteristic is not construed as isolated, they can be combined with each other to reach superior technique Effect.
The preparation of 1 bone renovating material of embodiment
According to the composition of the bone renovating material of table 1 each experimental group and control group, each component is weighed, by the adipose tissue It goes cellular matrix to crush, is dissolved in 30ml distilled water solution, the solution that 40ml includes fibroin albumen, palmityl tetrapeptide -7 is added, It mixes, is eventually adding 10ml indoles mountain valley with clumps of trees and bamboo green solution, mix, add distilled water to final volume 100ml, form uniform Bone Defect Repari material The gelling agent of material.
The amounts of components of 1 bone renovating material of table each experimental group and control group
Note: "/" indicates that this group is divided into 0;" () " indicates to replace this component with component in bracket.
The performance detection and application effect of 2 bone renovating material of embodiment
Each experimental group of the bone renovating material of embodiment 1 and control group are irradiated 60s using 785nm near infrared light, observation Evaluate the following performance indicator of each group bone renovating material.
(1) the performance indicator detection of each group bone renovating material
Mode of appearance: the porosity and pore size on the bone renovating material surface of each group under light microscopic and scanning electron microscopic observation, Whether uniformity.
Water absorption rate: weighing bone renovating material quality Wo value, be subsequently placed in the weighing bottle for filling deionized water, sufficiently molten It is swollen, surface moisture is blotted with filter paper, claims quality to obtain Wn value, calculating sample water absorption rate: water absorption rate (%)=[(Wn-Wo)/Wo] × 100
Compression modulus and stretch modulus: universal testing machine is utilized, the compression modulus and stretch modulus of bone renovating material are measured.
In summary performance indicator testing result, provides the Performance Score of each group bone renovating material, and various performance parameters are got over Good, score value is higher, and full marks 10 divide.
(2) biocompatibility of each group bone renovating material
Using mtt assay detection bone renovating material to the toxicity of the various kinds of cell of in vitro culture.Using experiment of nude mouse, bone is repaired Multiple material hydrogel adhesive is implanted to nude mice back sack made by leather, and structure observation is taken out after 4 weeks as a result, judging the life of each group bone renovating material Object compatibility, gives and scores, and biocompatibility is better, and score value is higher, and full marks 10 divide.
(3) rabbit radius wound animal model in body application effect
The building of rabbit radius wound animal model: taking the new zealand white rabbit of weight 2.5-3kg, after anesthesia, separates radius Locate blood vessel, tendon, exposure radius separates periosteum, amputates bone section with small-sized goose saw, bone defect position is made to reach long bone diameter 1.5 times, confirm by Micro-CT image, constructs rabbit radius wound animal model.
In body application effect: the radius site of injury of each experimental group of bone renovating material and control group implantation animal model, application Sewing-up cut after 785nm near infrared light 60s passes through the dyeing of bone pathology slice, micromorphology respectively at the 1st, 3, June It learns, molecular biology method, the safety and repair in body application of each experimental group of evaluation bone renovating material and control group. It using double-blind study, gives and scores, safety and repair are better, and score is higher, and full marks 10 divide.
The performance detection and application effect of the bone renovating material of the above each group the results are shown in Table 2.
The results of property and application effect of each experimental group of 2 bone renovating material of table and control group
Group Performance indicator Biocompatibility Bone wound repairing effect
Experimental group 1 10 10 10
Experimental group 2 9 10 8
Experimental group 3 9 10 8
Experimental group 4 9 10 9
Experimental group 5 9 10 9
Control group 1 4 10 4
Control group 2 9 10 5
Control group 3 5 10 4
Control group 4 3 10 3
Control group 5 4 10 2
Control group 6 9 10 5
Control group 7 9 10 5
Control group 8 9 10 5
Control group 9 9 10 4
Control group 10 9 10 4
Control group 11 4 10 3
Control group 12 8 10 6
Control group 13 9 10 6
Control group 14 8 10 6
Control group 15 8 10 6
Control group 16 9 10 6
As seen from the data in Table 2, the no significance difference of scoring of each group bone renovating material performance indicator and biocompatibility is tested Away from bone wound reparative experiment, the bone renovating material of experimental group can solidify rapidly in bone tissue wound site, formation and bone The adaptable three dimensional elasticity grid structure of defective tissue, realizes the quick healing at bone defect position, wherein being cured with experimental group 1 again Close effect preferably (scoring highest), followed by experimental group 4 and 5.
In control group, the bone renovating material hydrogel after 785nm near infrared light of control group 4 cannot be quickly solidified to form Three dimensional elasticity grid structure, performance indicator is worst, followed by control group 5,11 and 3, and the performance indicator of other control groups is opposite Preferably, each other without significant difference.The biocompatibility and experimental group indifference of control group.On bone wound repairing effect, Control group scoring is obviously not so good as experimental group, wherein worst with the scoring of the wound repair effect of control group 5, followed by 4 He of control group 11, it is again exactly control group 1,3,9 and 10.
The above result shows that the bone renovating material performance indexes of experimental group is excellent, biocompatibility is good, has good Good bone wound repair, can be used as the replacement graft of bone tissue.And part control group is although in performance indicator and life In terms of object compatibility and experimental group is without significant difference, but satisfactory result is unable to reach on bone wound repairing effect.
Thus it proves, the component that the present invention protects is the relationship of " collaboration mutually " and " not replaceable ", the quality of application Proportion is optimum range.
Above-mentioned detailed description is illustrating for the possible embodiments invented, and the embodiment is not to limit this hair Bright the scope of the patents, it is all without departing from equivalence enforcement or change of the invention, it should all be contained in the scope of the patents of the invention.
In addition, those skilled in the art can also the claims in the present invention scope of disclosure and spirit in do other forms and Various modifications, addition and replacement in details.Certainly, these spirit is done according to the present invention various modifications, addition and replacements It, all should be comprising within scope of the present invention Deng variation.

Claims (10)

1. a kind of bone renovating material, it is characterised in that: the bone renovating material main component includes that adipose tissue removes cell base Matter, palmityl tetrapeptide -7, fibroin albumen, heparin poloxamer and the indoles mountain valley with clumps of trees and bamboo are green, which passes through 785nm near infrared light Irradiation quickly solidifies to form the three dimensional elasticity grid structure being adapted with bone defect tissue.
2. bone renovating material according to claim 1, it is characterised in that: the quality of each component in the bone renovating material Proportion are as follows: adipose tissue removes 1~4 part of cellular matrix, -7 0.1~0.5 parts of palmityl tetrapeptide, 2~10 parts of fibroin albumen, heparin Green 0.01~0.5 part of 2~8 parts of poloxamer, the indoles mountain valley with clumps of trees and bamboo.
3. bone renovating material according to claim 1, it is characterised in that: the quality of each component in the bone renovating material Proportion is preferred are as follows: adipose tissue removes 2 parts of cellular matrix, -70.2 parts of palmityl tetrapeptide, 5 parts of fibroin albumen, heparin poloxamer 4 Part, green 0.05 part of the indoles mountain valley with clumps of trees and bamboo.
4. bone renovating material according to claim 1, it is characterized in that: sulfuric acid is further added in the bone renovating material Chondroitin, collagen, promotes the bioactie agent of bone growth one or more of at hyaluronic acid.
5. bone renovating material according to claim 1, it is characterized in that: hydroxyl is further added in the bone renovating material Apatite, calcium sulfate, calcium citrate, calcium phosphate, marine organisms bone shell and its extract.
6. a kind of preparation method of bone renovating material gelling agent described in claim 1, it is characterized in that: by the adipose tissue It goes cellular matrix to crush, is dissolved in 30ml distilled water solution, the solution that 40ml includes fibroin albumen, palmityl tetrapeptide -7 is added, It mixes, is eventually adding 10ml indoles mountain valley with clumps of trees and bamboo green solution, mix, add distilled water to final volume 100ml, form uniform Bone Defect Repari material The gelling agent of material.
7. the preparation method of bone renovating material according to claim 6, it is characterized in that: prepared by the bone renovating material Chondroitin sulfate is further added in journey, hyaluronic acid, collagen, promotes the bioactie agent of bone growth a kind of or several Kind.
8. the preparation method of bone renovating material according to claim 6, it is characterized in that: prepared by the bone renovating material Further be added in journey hydroxyapatite, calcium sulfate, calcium citrate, calcium phosphate, marine organisms bone shell and its extract.
9. the preparation method of bone renovating material according to claim 6, it is characterized in that: prepared by the bone renovating material The common antioxidant of pharmacy, wetting agent, solubilizer, pH adjusting agent are further added in journey.
10. bone renovating material according to claim 1, it is characterized in that: the bone renovating material is used for bone tissue wound Orthotopic transplantation reparation.
CN201910375018.2A 2019-04-24 2019-04-24 Bone repair material and preparation method thereof Active CN109999225B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114732904A (en) * 2022-04-26 2022-07-12 天津市口腔医院(天津市整形外科医院、南开大学口腔医院) Indocyanine green slow-release composite material with photo-thermal function and soft tissue repair function and preparation method thereof

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CN104707143A (en) * 2008-11-07 2015-06-17 克洛克斯科技公司 Combination of an oxidant and a photoactivator for the healing of wounds
CN106492281A (en) * 2016-11-17 2017-03-15 温州医科大学 A kind of biocompatibility bone graft and preparation method thereof
US20170340756A1 (en) * 2014-12-05 2017-11-30 Exchange Imaging Technologies Gmbh Pharmaceutical formulation having reverse thermal gelation properties for local delivery of nanoparticles
CN108888803A (en) * 2018-07-11 2018-11-27 蒋青 A kind of biological support and preparation method thereof, purposes and aquogel system
CN109529113A (en) * 2018-10-24 2019-03-29 温州医科大学 Low immunogenicity bone defect position packing material and preparation method thereof

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Publication number Priority date Publication date Assignee Title
CN104707143A (en) * 2008-11-07 2015-06-17 克洛克斯科技公司 Combination of an oxidant and a photoactivator for the healing of wounds
CN102989036A (en) * 2011-09-10 2013-03-27 浙江海正药业股份有限公司 Hydrogel containing heparin-poloxamer compound for anastomosis of blood vessel and preparation method thereof
US20170340756A1 (en) * 2014-12-05 2017-11-30 Exchange Imaging Technologies Gmbh Pharmaceutical formulation having reverse thermal gelation properties for local delivery of nanoparticles
CN106492281A (en) * 2016-11-17 2017-03-15 温州医科大学 A kind of biocompatibility bone graft and preparation method thereof
CN108888803A (en) * 2018-07-11 2018-11-27 蒋青 A kind of biological support and preparation method thereof, purposes and aquogel system
CN109529113A (en) * 2018-10-24 2019-03-29 温州医科大学 Low immunogenicity bone defect position packing material and preparation method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114732904A (en) * 2022-04-26 2022-07-12 天津市口腔医院(天津市整形外科医院、南开大学口腔医院) Indocyanine green slow-release composite material with photo-thermal function and soft tissue repair function and preparation method thereof

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