CN106620872A - Formula and preparation method of engineered bone scaffold - Google Patents

Formula and preparation method of engineered bone scaffold Download PDF

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Publication number
CN106620872A
CN106620872A CN201710036720.7A CN201710036720A CN106620872A CN 106620872 A CN106620872 A CN 106620872A CN 201710036720 A CN201710036720 A CN 201710036720A CN 106620872 A CN106620872 A CN 106620872A
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Prior art keywords
polyvinyl alcohol
calcium phosphate
bone
biphasic calcium
powder
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CN201710036720.7A
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CN106620872B (en
Inventor
宋岳
毕龙
曾庆丰
林楷丰
张帅帅
刘斌
何树
裴国献
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Fourth Military Medical University FMMU
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Fourth Military Medical University FMMU
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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
    • A61L27/40Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • 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
    • A61L27/54Biologically active materials, e.g. therapeutic substances
    • 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE 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
    • B33Y70/00Materials specially adapted for additive manufacturing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B33ADDITIVE MANUFACTURING TECHNOLOGY
    • B33YADDITIVE 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
    • B33Y80/00Products made by additive manufacturing
    • 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
    • A61L2430/40Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking

Abstract

The invention discloses a formula and a preparation method of an engineered bone scaffold. The formula comprises polyvinyl alcohol powder, deionized water and two-phase calcium phosphate. Firstly, 0.15 g/ml of polyvinyl alcohol colloid is prepared by dissolving polyvinyl alcohol in deionized water, then two-phase calcium phosphate-polyvinyl alcohol paste tissue is formed by compounding two-phase calcium phosphate and polyvinyl alcohol colloid, the paste as a raw material is printed by a biological material printer, and a two-phase calcium phosphate-polyvinyl alcohol tissue engineered bone scaffold material with inducing osteogenesis capacity is prepared. The bone tissue engineering scaffold can combine growth factors and medicines, has a slow release effect and has effective potential clinical use value.

Description

The formula and preparation method of Engineering Bone support
Technical field
The invention belongs to pharmaceutical technology field, more particularly to the formula and preparation method of Engineering Bone support.
Background technology
Cranial defect, bone does not connect on a large scale, are very common problems in curative activity.Be common in wound, tumor, infection, Congenital or developmental character disease etc..Which is always a global problem of field of orthopaedics, not yet obtains effectively solving so far.Mesh Front conventional restorative procedure has autologous bone transplanting, allogenic bone transplantation, synthetic substitute etc., but these methods in having for area Sex-limited, more complication and sequela, antigenicity, biocompatibility, biological activity, biodegradability and with host bone The aspects such as mechanical matching, service life all have respective shortcoming, limit its clinical practice, it is difficult to reach satisfied effect.Group Knit the proposition of engineering, set up and development be to tissue in surgical field, organ defect and dysfunction traditional therapy and The revolution of pattern.It is brand-new Therapeutic mode using tissue engineering ways and means repair tissue defect, with wide Application prospect, be the hot issue of current medical circle research;Its final purpose is that preferable offer, wide material sources, answers The bioactivity osseous tissue determined with easy, curative effect, bone tissue engineer are wherein particularly important with the neck for representing meaning Domain, for the therapeutic effect of the diseases such as Cranial defect that various clinical common causes are caused fundamentally is improved, osseous tissue work Journey breaches conventional Therapeutic mode, there is provided brand-new thinking and method.
Due to being presented irregularly shaped Cranial defect shape, external preforming bone-grafting material is difficult in adapt to Cranial defect shape more, Interval is formed between normal sclerotin, so as to affect tissue engineered bone support conduction, the appearance of 3D printing technique can be fine Solution individualized treatment this difficult problem.3D printing technique is referred to as " idea factories on desktop ".First will be produced with related software Product drawing is converted into 3D rendering data and uploads computer, after being put into corresponding material, printing head will according to view data by Thing is printed by layer, then is stacked and is become a stereo article.Due to adopting " addition manufacturing technology " (additive Manufacturing raw material and artificial), therefore is more saved, and the article for coming in every shape can be made.In theory, as long as The moulding that computer can be designed that, 3D printer can print out.Tele-medicine, personalized medicine are the development of World Medical Trend.3D printing technique can produce various artificial organs and tissue using different " ink " materials, can meet clinical trouble Person is individual to be required.Metal, resin, Gypsum Fibrosum, ceramics, macromolecule, biomacromolecule etc. be creatively applied to 3D printing with Production biological product.With medical skill individualized development, technique is widely used for making accurately suffers from bone model, spends body The bone defect healing body of individuation customized.Biomaterial printer is state-of-the-art without silk printing technique using the world of original creation, can The parameters such as Cranial defect size, shape and internal voids according to Orthopedic Clinical patient, accurately customize out physicochemical characteristicses and outward appearance knot The bionical biodegradable artificial bone of structure.
Bone tissue engineering stent material composite growth factor or medicine can improve implantation timbering material Bone Defect Repari effect, But in clinical case, the bony defect of required reparation is often larger, defect perilesional is susceptible to infection, and single is given Give the somatomedin or medicine of heavy dose to be difficult to play preferable effect, or even be harmful to body.So, in addition it is also necessary to growth The factor or medicine carry out slow release.Existing result of study shows that polyvinyl alcohol colloid has a good slow release effect, and The application having in terms of slow release, therefore available polyethylene alcohol colloid prepares tissue engineered bone support as binding agent and slow-released carrier is combined Somatomedin and medicine implantation Cranial defect local play a role.
Therefore, develop and can print via 3D printer and bionical have by the imaging data of Cranial defect patient The biodegradable artificial bone of the sustained release growth factor and medicine, and the bone tissue engineering stent material of supporting role is produced with weight Want meaning.
The content of the invention
The technical problem to be solved is:The formula and preparation method of Engineering Bone support, the present invention are provided Cranial defect individual is solved well treats this difficult problem.
To solve above-mentioned technical problem, the technical scheme is that:The formula of Engineering Bone support, it is characterised in that:Adopt Use formula as below:Using formula as below:Pva powder, deionized water, biphasic calcium phosphate powder, described polyvinyl alcohol powder Last alcoholysis degree is 99+%.
2nd, the preparation method of Engineering Bone support according to claim 1, it is characterised in that:Carry out according to the following steps:
(1) it is made into:Pva powder is dissolved in into the polyvinyl alcohol colloid that deionized water is made into 0.15g/ml first;
(2) mix:Polyvinyl alcohol colloid in (1) is mixed with biphasic calcium phosphate powder;
(3) stir:Complex in (2) is stirred, biphasic calcium phosphate and polyvinyl alcohol mastic line and staff control is obtained;
(4) it is loaded into:Patient bone defect model three dimensional file is loaded into into biomaterial printer;
(5) print:Biphasic calcium phosphate will be obtained and biomaterial printer will be poured into polyvinyl alcohol mastic line and staff control, then Printed by biomaterial printer and the biphasic calcium phosphate-polyvinyl alcohol tissue engineered bone with induced osteogenesis ability is obtained Frame material.
(6) freeze thawing:The biphasic calcium phosphate that (5) are drawn-polyvinyl alcohol bone tissue engineering scaffold carries out subzero 20 Degree, the frost of 10~20 hours or so, then the room temperature defrosting of 10~20 hours.
(7) it is dried;By the biphasic calcium phosphate after (6) freeze thawing-polyvinyl alcohol bone tissue engineering scaffold lyophilization Machine is dried 2~5 hours, i.e. Engineering Bone rack forming.
Further, in described (2) blend step, biphasic calcium phosphate powder and polyvinyl alcohol colloid are according to 1g:1.5g ratio It is compounded to form biphasic calcium phosphate-polyvinyl alcohol mastic tissue.
Pva powder:Organic compound, extremely safe macromolecule organic, with good biocompatibility.
Deionized water:For fusion agent, high-purity water.
Biphasic calcium phosphate powder:For bone alternate material, with good biocompatibility.
The formula and preparation method of the Engineering Bone support, it is empty by the Cranial defect size of clinical patients, shape and inside The parameters such as gap, accurately customize out the bionical biodegradable artificial bone of physicochemical characteristicses and surface structure, prepare with ossification 3D printing biphasic calcium phosphate-polyvinyl alcohol bone tissue engineering scaffold, and the tissue engineered bone support can composite growth because Son and medicine simultaneously reach the effect of slow release, it has been investigated that the 3D printing biphasic calcium phosphate-poly- second built according to this component ratio Enol bone tissue engineering scaffold has significant rush ossification, can surrounding be produced into mesenchymal stem cells MSCs Change is acted on, and can induce these cell Osteoblast Differentiation, finally plays ossification, and can with composite growth factor and medicine, The effect of slow release is reached, the present invention can be very good solution Cranial defect individual and treat this difficult problem.
Description of the drawings
Fig. 1 is preparation flow figure of the present invention
Specific embodiment
Hereinafter, various specific details are elaborated, to provide the saturating of the concept to constituting described embodiment basis Thorough understanding.However, it will be apparent to those skilled in the art that described embodiment can not have these specific details In it is some or all in the case of putting into practice.In other cases, well-known process step is not specifically described.
Embodiment 1
The formula of the Engineering Bone support that the 1st, the present embodiment is enumerated, is made up of the raw material of following weight:Pva powder, go Ionized water, biphasic calcium phosphate powder, described pva powder alcoholysis degree are 99+%.
2nd, the preparation method of Engineering Bone support according to claim 1, it is characterised in that:Carry out according to the following steps:
(1) it is made into:Pva powder is dissolved in into the polyvinyl alcohol colloid that deionized water is made into 0.15g/ml first;
(2) mix:Polyvinyl alcohol colloid in (1) is mixed with biphasic calcium phosphate powder;
(3) stir:Complex in (2) is stirred, biphasic calcium phosphate and polyvinyl alcohol mastic line and staff control is obtained;
(4) it is loaded into:Patient bone defect model three dimensional file is loaded into into biomaterial printer;
(5) print:Biphasic calcium phosphate will be obtained and biomaterial printer will be poured into polyvinyl alcohol mastic line and staff control, then Printed by biomaterial printer and the biphasic calcium phosphate-polyvinyl alcohol tissue engineered bone with induced osteogenesis ability is obtained Frame material.
(6) freeze thawing:The biphasic calcium phosphate that (5) are drawn-polyvinyl alcohol bone tissue engineering scaffold carries out subzero 20 Degree, the frost of 10 hours or so, then the room temperature defrosting of 10 hours.
(7) it is dried;By the biphasic calcium phosphate after (6) freeze thawing-polyvinyl alcohol bone tissue engineering scaffold lyophilization Machine is dried 2 hours, i.e. Engineering Bone rack forming.
Further, in described (2) blend step, biphasic calcium phosphate powder and polyvinyl alcohol colloid are according to 1g:1.5g ratio It is compounded to form biphasic calcium phosphate-polyvinyl alcohol mastic tissue.
Pva powder:Organic compound, extremely safe macromolecule organic, with good biocompatibility.
Deionized water:For fusion agent, high-purity water.
Biphasic calcium phosphate powder:For bone alternate material, with good biocompatibility.
The formula and preparation method of the Engineering Bone support, it is empty by the Cranial defect size of clinical patients, shape and inside The parameters such as gap, accurately customize out the bionical biodegradable artificial bone of physicochemical characteristicses and surface structure, prepare with ossification 3D printing biphasic calcium phosphate-polyvinyl alcohol bone tissue engineering scaffold, and the tissue engineered bone support can composite growth because Son and medicine simultaneously reach the effect of slow release, it has been investigated that the 3D printing biphasic calcium phosphate-poly- second built according to this component ratio Enol bone tissue engineering scaffold has significant rush ossification, can surrounding be produced into mesenchymal stem cells MSCs Change is acted on, and can induce these cell Osteoblast Differentiation, finally plays ossification, and can with composite growth factor and medicine, The effect of slow release is reached, the present invention can be very good solution Cranial defect individual and treat this difficult problem.
Embodiment 2
The formula of the Engineering Bone support that the 1st, the present embodiment is enumerated, is made up of the raw material of following weight:Pva powder, go Ionized water, biphasic calcium phosphate powder, described pva powder alcoholysis degree are 99+%.
2nd, the preparation method of Engineering Bone support according to claim 1, it is characterised in that:Carry out according to the following steps:
(1) it is made into:Pva powder is dissolved in into the polyvinyl alcohol colloid that deionized water is made into 0.15g/ml first;
(2) mix:Polyvinyl alcohol colloid in (1) is mixed with biphasic calcium phosphate powder;
(3) stir:Complex in (2) is stirred, biphasic calcium phosphate and polyvinyl alcohol mastic line and staff control is obtained;
(4) it is loaded into:Patient bone defect model three dimensional file is loaded into into biomaterial printer;
(5) print:Biphasic calcium phosphate will be obtained and biomaterial printer will be poured into polyvinyl alcohol mastic line and staff control, then Printed by biomaterial printer and the biphasic calcium phosphate-polyvinyl alcohol tissue engineered bone with induced osteogenesis ability is obtained Frame material.
(6) freeze thawing:The biphasic calcium phosphate that (5) are drawn-polyvinyl alcohol bone tissue engineering scaffold carries out subzero 20 Degree, the frost of 20 hours or so, then the room temperature defrosting of 20 hours.
(7) it is dried;By the biphasic calcium phosphate after (6) freeze thawing-polyvinyl alcohol bone tissue engineering scaffold lyophilization Machine is dried 5 hours, i.e. Engineering Bone rack forming.
Further, in described (2) blend step, biphasic calcium phosphate powder and polyvinyl alcohol colloid are according to 1g:1.5g ratio It is compounded to form biphasic calcium phosphate-polyvinyl alcohol mastic tissue.
Pva powder:Organic compound, extremely safe macromolecule organic, with good biocompatibility.
Deionized water:For fusion agent, high-purity water.
Biphasic calcium phosphate powder:For bone alternate material, with good biocompatibility.
The formula and preparation method of the Engineering Bone support, it is empty by the Cranial defect size of clinical patients, shape and inside The parameters such as gap, accurately customize out the bionical biodegradable artificial bone of physicochemical characteristicses and surface structure, prepare with ossification 3D printing biphasic calcium phosphate-polyvinyl alcohol bone tissue engineering scaffold, and the tissue engineered bone support can composite growth because Son and medicine simultaneously reach the effect of slow release, it has been investigated that the 3D printing biphasic calcium phosphate-poly- second built according to this component ratio Enol bone tissue engineering scaffold has significant rush ossification, can surrounding be produced into mesenchymal stem cells MSCs Change is acted on, and can induce these cell Osteoblast Differentiation, finally plays ossification, and can with composite growth factor and medicine, The effect of slow release is reached, the present invention can be very good solution Cranial defect individual and treat this difficult problem.
The present invention is not limited to above-mentioned specific embodiment, one of ordinary skill in the art from above-mentioned design, Without performing creative labour, a variety of conversion made, it is within the scope of the present invention.

Claims (3)

1. the formula of Engineering Bone support, it is characterised in that:Using formula as below:Pva powder, deionized water, two-phase phosphoric acid Calcium powder, described pva powder alcoholysis degree are 99+%.
2. the preparation method of the Engineering Bone support described in claim 1 is prepared, it is characterised in that:Carry out according to the following steps:
(1) it is made into:Pva powder is dissolved in into the polyvinyl alcohol colloid that deionized water is made into 0.15g/ml first;
(2) mix:Polyvinyl alcohol colloid in (1) is mixed with biphasic calcium phosphate powder;
(3) stir:Complex in (2) is stirred, biphasic calcium phosphate and polyvinyl alcohol mastic line and staff control is obtained;
(4) it is loaded into:Patient bone defect model three dimensional file is loaded into into biomaterial printer;
(5) print:Biphasic calcium phosphate in (3) is poured into biomaterial printer with polyvinyl alcohol mastic line and staff control, Ran Houtong Cross biomaterial printer and print prepared biphasic calcium phosphate-polyvinyl alcohol tissue engineered bone support with induced osteogenesis ability Material.
(6) freeze thawing:The biphasic calcium phosphate that (5) are drawn-polyvinyl alcohol bone tissue engineering scaffold carries out minus 20 degrees, and 10 The frost of~20 hours or so, then the room temperature defrosting of 10~20 hours.
(7) it is dried;Biphasic calcium phosphate after (6) freeze thawing-polyvinyl alcohol bone tissue engineering scaffold is dry with freezer dryer Dry 2~5 hours, i.e. Engineering Bone rack forming.
3. the preparation method of Engineering Bone support according to claim 2, it is characterised in that double in described (2) blend step Calcium phosphate phase powder is with polyvinyl alcohol colloid according to 1g:1.5g ratios are compounded to form biphasic calcium phosphate-polyvinyl alcohol mastic group Knit.
CN201710036720.7A 2017-01-18 2017-01-18 The formula and preparation method of Engineering Bone bracket Expired - Fee Related CN106620872B (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108478873A (en) * 2018-04-25 2018-09-04 信阳师范学院 A kind of preparation method of biphasic calcium phosphate plural gel
CN108478882A (en) * 2018-04-25 2018-09-04 信阳师范学院 A kind of preparation method of compound bone holder material
CN109133907A (en) * 2018-08-16 2019-01-04 迈海新型材料科技(固安)有限公司 A kind of artificial bone and preparation method thereof comprising hydroxyapatite crystal whisker and biphase calcium phosphor
CN115463254A (en) * 2022-09-06 2022-12-13 点云生物(杭州)有限公司 Spongy bone-like defect filler and preparation method thereof

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CN101721740A (en) * 2008-10-16 2010-06-09 上海国睿生命科技有限公司 Bone tissue engineering bracket material and preparation method and application thereof
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CN101721740A (en) * 2008-10-16 2010-06-09 上海国睿生命科技有限公司 Bone tissue engineering bracket material and preparation method and application thereof
WO2015072806A1 (en) * 2013-11-18 2015-05-21 고려대학교산학협력단 Double porous synthetic bone wedge and method for manufacturing same

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108478873A (en) * 2018-04-25 2018-09-04 信阳师范学院 A kind of preparation method of biphasic calcium phosphate plural gel
CN108478882A (en) * 2018-04-25 2018-09-04 信阳师范学院 A kind of preparation method of compound bone holder material
CN109133907A (en) * 2018-08-16 2019-01-04 迈海新型材料科技(固安)有限公司 A kind of artificial bone and preparation method thereof comprising hydroxyapatite crystal whisker and biphase calcium phosphor
CN115463254A (en) * 2022-09-06 2022-12-13 点云生物(杭州)有限公司 Spongy bone-like defect filler and preparation method thereof

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