CN114699559A - Construction method of cartilage scaffold - Google Patents

Construction method of cartilage scaffold Download PDF

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Publication number
CN114699559A
CN114699559A CN202210270276.6A CN202210270276A CN114699559A CN 114699559 A CN114699559 A CN 114699559A CN 202210270276 A CN202210270276 A CN 202210270276A CN 114699559 A CN114699559 A CN 114699559A
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Prior art keywords
cartilage
scaffold
different areas
hydrogel
elastic modulus
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CN202210270276.6A
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Chinese (zh)
Inventor
赵振民
王关卉儿
杨欣
薛红宇
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Peking University Third Hospital Peking University Third Clinical Medical College
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Peking University Third Hospital Peking University Third Clinical Medical College
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Priority to CN202210270276.6A priority Critical patent/CN114699559A/en
Publication of CN114699559A publication Critical patent/CN114699559A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials 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
    • A61L27/38—Materials 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 containing added animal cells
    • A61L27/3804—Materials 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 containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3817—Cartilage-forming cells, e.g. pre-chondrocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials 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
    • A61L27/38—Materials 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 containing added animal cells
    • A61L27/3804—Materials 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 containing added animal cells characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells
    • A61L27/3834—Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials 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
    • A61L27/38—Materials 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 containing added animal cells
    • A61L27/3839—Materials 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 containing added animal cells characterised by the site of application in the body
    • A61L27/3843—Connective tissue
    • A61L27/3852—Cartilage, e.g. meniscus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/52—Hydrogels or hydrocolloids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y10/00—Processes of additive manufacturing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y70/00—Materials specially adapted for additive manufacturing
    • B33Y70/10—Composites of different types of material, e.g. mixtures of ceramics and polymers or mixtures of metals and biomaterials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B33—ADDITIVE MANUFACTURING TECHNOLOGY
    • B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
    • B33Y80/00—Products made by additive manufacturing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus

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  • Health & Medical Sciences (AREA)
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  • Oral & Maxillofacial Surgery (AREA)
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  • Manufacturing & Machinery (AREA)
  • Urology & Nephrology (AREA)
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Abstract

The invention provides a construction method of a cartilage scaffold, belonging to the technical field of medical materials. According to the method, finite element analysis is carried out according to a three-dimensional CAD model of the cartilage support to be printed, and the stress condition of the cartilage support at different parts is determined; determining the elastic modulus of the cartilage scaffold in different areas according to the stress conditions of the cartilage scaffold in different parts, and further determining the ratio of cartilage balls to hydrogel in different areas; according to the invention, gradient 3D printing is carried out according to the ratio of cartilage balls to hydrogel in different areas to obtain the cartilage scaffold. After the elastic modulus of the cartilage support in different areas is obtained through analysis, the stress and deformation of the cartilage support are optimized by configuring the elastic modulus of the different areas, and the stress and deformation of the cartilage support are in the optimal state.

Description

Construction method of cartilage scaffold
Technical Field
The invention relates to the technical field of medical materials, in particular to a construction method of a cartilage scaffold.
Background
The elastic cartilage is used as a contour filling material and has wide application scenes and important application value in the fields of plastic surgery and cosmetic surgery. Taking the nasal plastic as an example, the nasal reconstruction and the nasal cosmetic plastic surgery have higher requirements on the strength and the shape of the stent structure, and the current commonly used stent materials include organic composite prosthesis, auricular cartilage, costal cartilage and the like. The nose prosthesis is made of polymer organic compounds, and the polymer organic compound nose prosthesis can generate relatively serious inflammatory reaction in a region rich in blood supply due to rejection reaction because of the characteristics that the external nose is relatively lack of blood supply and the covering skin is thin; the auricular cartilage and the costal cartilage are obtained by self, and the cartilage supply area and the cartilage receiving area are different in mechanical environment and the cartilage support is partially deformed due to different stress conditions, so that complications such as bending, absorption, contour change and the like frequently occur after autologous cartilage transplantation.
Disclosure of Invention
The invention aims to provide a construction method of a cartilage support, and the nasal cartilage support constructed by the construction method has good stress and deformation performance and is suitable for a mechanical environment of a stressed area.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a construction method of a cartilage scaffold, which comprises the following steps:
1) carrying out finite element analysis according to the three-dimensional CAD model of the cartilage support to be printed, and determining the stress condition of the cartilage support at different parts;
2) determining the elastic modulus of the cartilage scaffold in different areas according to the stress conditions of the cartilage scaffold in different parts;
3) determining the ratio of the cartilage ball to the hydrogel in different areas according to the elastic modulus of the cartilage support in different areas;
4) and performing gradient 3D printing according to the ratio of the cartilage ball to the hydrogel in different areas to obtain the cartilage scaffold.
Preferably, the three-dimensional CAD model of the cartilage scaffold to be printed in the step 1) is obtained by constructing imaging data; the imaging data comprises CT, MR and 3D structured light body surface scanning results.
Preferably, in step 1), the finite element analysis comprises nonlinear finite element analysis.
Preferably, the nonlinear finite element analysis includes deformation analysis, stress analysis and elastic modulus influence analysis.
Preferably, before step 3), the method further comprises the step of determining the elastic modulus of the hydrogel in different concentrations and the cartilage ball in different volume ratios through pre-experiments.
Preferably, the gradient printing in step 4) includes needle printing; the pinhead printing is carried out by adopting a printer with multiple pinheads; each needle is loaded with a region of desired concentration of hydrogel and cartilage balls.
Preferably, the chondrocytes in step 4) are derived from chondrocytes or adipose-derived mesenchymal stem cells.
The invention provides a construction method of a cartilage support, which is characterized in that finite element analysis is carried out according to a three-dimensional CAD model of the cartilage support to be printed, and the stress condition of the cartilage support at different parts is determined; determining the elastic modulus of the cartilage scaffold in different areas according to the stress conditions of the cartilage scaffold in different parts, and further determining the ratio of cartilage balls to hydrogel in different areas; according to the invention, gradient 3D printing is carried out according to the ratio of cartilage balls to hydrogel in different areas, so as to obtain the cartilage scaffold. After the elastic modulus of the cartilage support in different areas is obtained through analysis, the stress and deformation of the cartilage support are optimized by configuring the elastic modulus of the different areas, and the stress and deformation of the cartilage support are in the optimal state.
Drawings
FIG. 1 is a flow chart of example 1.
Detailed Description
The invention provides a construction method of a cartilage scaffold, which comprises the following steps:
1) carrying out finite element analysis according to the three-dimensional CAD model of the cartilage support to be printed, and determining the stress condition of the cartilage support at different parts;
2) determining the elastic modulus of the cartilage scaffold in different areas according to the stress conditions of the cartilage scaffold in different parts;
3) determining the ratio of the cartilage ball to the hydrogel in different areas according to the elastic modulus of the cartilage support in different areas;
4) and performing gradient 3D printing according to the ratio of the cartilage ball to the hydrogel in different areas to obtain the cartilage scaffold.
According to the method, finite element analysis is carried out according to a three-dimensional CAD model of the cartilage support to be printed, and the stress condition of the cartilage support at different parts is determined.
In the invention, the three-dimensional CAD model of the cartilage scaffold to be printed is preferably obtained by constructing imaging data; the imaging data preferably includes CT, facial MR, and 3D structured light body surface scans. In the present invention, the finite element analysis preferably includes nonlinear finite element analysis; the nonlinear finite element analysis preferably includes deformation analysis, stress analysis, and elastic modulus influence analysis. The basis for finite element analysis in the invention includes the position relationship between the cartilage scaffold to be printed and the adjacent skin, muscle and cortical bone. In the present invention, the cartilage scaffold includes a nasal cartilage scaffold or an ear cartilage scaffold.
After the stress conditions of the cartilage scaffold at different parts are determined, the elastic modulus of the cartilage scaffold in different areas is determined according to the stress conditions of the cartilage scaffold at different parts.
After the elastic modulus of the cartilage scaffold in different areas is determined, the ratio of the cartilage ball to the hydrogel in different areas is determined according to the elastic modulus of the cartilage scaffold in different areas. Before the ratio of the cartilage ball to the hydrogel in different areas is determined according to the elastic modulus of the cartilage support in different areas, the invention preferably further comprises the steps of determining the elastic modulus of the hydrogel in different concentrations and the cartilage ball in different volume ratios through a pre-experiment, and then determining the ratio of the cartilage ball to the hydrogel in different areas according to the elastic modulus of the cartilage support in different areas. In the present invention, the hydrogel preferably comprises a silk fibroin hydrogel.
After the proportions of the cartilage ball and the hydrogel in different areas are determined, gradient 3D printing is carried out according to the proportions of the cartilage ball and the hydrogel in different areas, and the cartilage scaffold is obtained. In the present invention, the gradient printing mode preferably includes needle printing; the needle printing is preferably performed by a printer with multiple needles; each needle is loaded with a region of the desired concentration of hydrogel and chondrocytes.
In the present invention, the chondrocyte is preferably derived from chondrocytes or adipose-derived mesenchymal stem cells. In the present invention, the chondrocytes are preferably derived from the patient himself; the adipose-derived mesenchymal stem cells are from the patient or from allochthogenesis. The preparation method of the cartilage ball is not particularly limited, and the conventional method in the field can be adopted.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
Example 1
The flow chart is shown in fig. 1.
1) Carrying out finite element analysis on a nasal skeleton to be printed to obtain stress condition data of the nasal skeleton; analyzing the stress condition of the obtained nose skeleton to obtain the distribution data of the elastic modulus of the nose skeleton, and designing a 3D printing mechanical partition according to the distribution data;
2) determining the elastic modulus of hydrogel with different concentrations and the cartilage ball with different volume proportions through a pre-experiment, and determining the proportion of the cartilage ball and the hydrogel in different areas according to the elastic modulus of the cartilage support in different areas;
3) obtaining rabbit ear cartilage, culturing the rabbit ear flexible tubes to obtain chondrocytes, and further culturing the chondrocytes to obtain cartilage balls;
4) preparing photocrosslinkable silk fibroin hydrogel with different concentrations according to a 3D printing mechanical partition and a pre-experiment result;
5) adding a photoinitiator and cartilage balls with corresponding concentrations into photocrosslinkable silk fibroin hydrogel with different concentrations to obtain gel on the cartilage balls, and performing gradient 3D printing to obtain the cartilage scaffold.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (7)

1. A construction method of a cartilage scaffold comprises the following steps:
1) carrying out finite element analysis according to the three-dimensional CAD model of the cartilage support to be printed, and determining the stress condition of the cartilage support at different parts;
2) determining the elastic modulus of the cartilage scaffold in different areas according to the stress conditions of the cartilage scaffold in different parts;
3) determining the ratio of the cartilage ball to the hydrogel in different areas according to the elastic modulus of the cartilage support in different areas;
4) and performing gradient 3D printing according to the ratio of the cartilage ball to the hydrogel in different areas to obtain the cartilage scaffold.
2. The construction method according to claim 1, characterized in that the three-dimensional CAD model of the cartilage scaffold to be printed in step 1) is constructed by imaging data; the imaging data comprises CT, MR and 3D structured light body surface scanning results.
3. The construction method according to claim 1, wherein in step 1), the finite element analysis comprises nonlinear finite element analysis.
4. The method of construction of claim 3 wherein the nonlinear finite element analysis includes deformation analysis, stress analysis, and elastic modulus influence analysis.
5. The method for constructing the cartilage ball of claim 1, wherein before the step 3), the method further comprises the step of determining the elastic modulus of different concentrations of hydrogel and different volume ratios of the cartilage ball through pre-experiments.
6. The building method according to claim 1, wherein the gradient printing manner in the step 4) comprises needle printing; the pinhead printing is carried out by adopting a printer with multiple pinheads; each needle is loaded with a region of desired concentration of hydrogel and cartilage balls.
7. The method for constructing according to claim 1, wherein the chondrocytes in step 4) are derived from chondrocytes or adipose-derived mesenchymal stem cells.
CN202210270276.6A 2022-03-18 2022-03-18 Construction method of cartilage scaffold Pending CN114699559A (en)

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Citations (6)

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Publication number Priority date Publication date Assignee Title
CN103948457A (en) * 2014-05-08 2014-07-30 上海交通大学医学院附属第九人民医院 Method for constructing regenerated nerve vascularized bones, cartilages, joints or body surface organs
CN104398320A (en) * 2014-11-20 2015-03-11 杭州电子科技大学 Method of assembling artificial laryngeal cartilage support in cell-controlled manner
CN107058216A (en) * 2016-10-12 2017-08-18 武汉枫霖科技有限公司 A kind of method for promoting articular cartilage tissue to grow
CN109082407A (en) * 2018-06-14 2018-12-25 广州思晋生物科技有限公司 A kind of mescenchymal stem cell is at chondrocyte induction differential medium
CN111676190A (en) * 2020-06-09 2020-09-18 生物岛实验室 Inducer for differentiation of stem cells into chondroblasts and application thereof
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CN104398320A (en) * 2014-11-20 2015-03-11 杭州电子科技大学 Method of assembling artificial laryngeal cartilage support in cell-controlled manner
CN107058216A (en) * 2016-10-12 2017-08-18 武汉枫霖科技有限公司 A kind of method for promoting articular cartilage tissue to grow
CN109082407A (en) * 2018-06-14 2018-12-25 广州思晋生物科技有限公司 A kind of mescenchymal stem cell is at chondrocyte induction differential medium
CN111676190A (en) * 2020-06-09 2020-09-18 生物岛实验室 Inducer for differentiation of stem cells into chondroblasts and application thereof
KR20220030564A (en) * 2020-09-03 2022-03-11 서울과학기술대학교 산학협력단 Functional hydrogel cross-linked with tannic acid and alginic acid and its manufacturing method

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