WO2018164594A1 - Procédé de fabrication d'implants osseux composites, procédé de fabrication de matière première en poudre pour de tels implants, ladite matière première en poudre et ledit implant osseux - Google Patents

Procédé de fabrication d'implants osseux composites, procédé de fabrication de matière première en poudre pour de tels implants, ladite matière première en poudre et ledit implant osseux Download PDF

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Publication number
WO2018164594A1
WO2018164594A1 PCT/PL2018/050008 PL2018050008W WO2018164594A1 WO 2018164594 A1 WO2018164594 A1 WO 2018164594A1 PL 2018050008 W PL2018050008 W PL 2018050008W WO 2018164594 A1 WO2018164594 A1 WO 2018164594A1
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WO
WIPO (PCT)
Prior art keywords
raw material
hydroxyapatite
implant
fibroin
powdered
Prior art date
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PCT/PL2018/050008
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English (en)
Inventor
Maria MAŁYSA
Tadeusz Chudoba
Elżbieta PIETRZYKOWSKA
Agnieszka CHODARA
Witold Lojkowski
Jacek KROPIWNICKI
Michał CHARKIEWICZ
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Instytut Wysokich Ciśnień Polskiej Akademii Nauk
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Publication of WO2018164594A1 publication Critical patent/WO2018164594A1/fr

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Classifications

    • 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
    • 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
    • A61L27/3604—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 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
    • 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
    • A61L27/3683—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3691—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 subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • 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
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention regards a method of manufacturing composite bone implants containing synthetic hydroxyapatite and fibroin, a method of manufacturing a powdered raw material for such composite bone implants, a powdered raw material for implants of this kind, and a composite bone implant containing synthetic hydroxyapatite and fibroin.
  • cortical bone tissue is characterized by compressive strength between 100 and 230 MPa, bending strength between 50 and 150 MPa and Young's modulus in the range from 7 to 30 GPa. These data are disclosed in Jan Henkel et al. perennialBone Regeneration Based on Tissue Engineering Conceptions - A 21st Century Perspective" [Bone Research (2013) 1 , pp. 216-248].
  • a bone implant consisting entirely of synthetic hydroxyapatite has a high biocompatibility and bioactivity, but at the same time has a low bending strength and too high Young's modulus.
  • a composite consisting of crystalline hydroxyapatite and a polymer is often used, both synthetic and natural, for example a natural silk building protein, i.e. fibroin.
  • Fibroin is biocompatible and resorbable.
  • fibroin naturally occurs in the form of fibres characterized by high mechanical strength.
  • the use of fibrous structure for purposes of bone tissue regeneration is also beneficial from a biological point of view.
  • Composite structures containing fibroin and synthetic hydroxyapatite have been the subject of a number of patent applications.
  • Publication WO 2009/100280 discloses a method of manufacturing mixtures consisting of silk and hydroxyapatite, from which when in a liquid form solid structures of required shapes can be cast or which can be used in a form of special paste for treating bones and teeth.
  • the hydroxyapatite content of such a mixture can vary from 0.1% to 90%.
  • the preparation of the mixture starts with boiling of silkworm cocoons in an aqueous salt solution to remove the second silk building protein, i.e. sericin, from silk fibres.
  • the silk which has been purified from the serine is dissolved in the lithium bromide solution (LiBr) and then it is separated from the solution by dialysis and centrifugation.
  • LiBr lithium bromide solution
  • the thus-separated fibroin is freeze-dried and then dissolved in hexafluoro isopropanol (HFIP).
  • HFIP hexafluoro isopropanol
  • the synthetic hydroxyapatite is added to the fibroin solution in the desired proportion and a liquid substance is obtained which is suitable for casting during which a solid form is obtained by evaporation.
  • the material thus produced has a low mechanical strength, and its average Young's modulus during compression for the material with 30% by weight of hydroxyapatite is 84.2 MPa.
  • Publication CN 02058907 discloses a method of manufacturing bone implants containing hydroxyapatite.
  • a wollastonite suspension is chemically prepared, then dried to powder.
  • Fibroin is dissolved in calcium nitrate solution.
  • fibroin with calcium nitrate sodium phosphate and sodium hydroxide a water-diluted wollastonite is added.
  • the obtained powder contains from 0 to 30% by weight of wollastonite, from 25 to 35% of fibroin and from 40 to 60% of hydroxyapatite.
  • the powder is then cold pressed isostatically.
  • the compressive strength of the thus obtained composite is 90 MPa.
  • Publication CN 102000362 discloses a process of manufacturing porous scaffolds containing fibroin and nano-hydroxyapatite in an amount of 30 to 90% by weight.
  • fibroin is first dissolved in a three-component system of calcium chloride-ethanol-water, and then diammonium phosphate, ammonium hydroxide and ammonia are added to the solution.
  • the resulting precipitate, containing fibroin and hydroxyapatite is dried and grinded.
  • the powder is mixed with water to form a paste, to which the carboxymethyl cellulose is added and then by lyophi- lisation a porous structure is obtained.
  • the thus-obtained scaffold is characterized by an open porosity of 40%, but at the same time has a very low compressive (from 3 to 3.69MPa) and bending (from 3 to 4.75MPa) strength.
  • the aim of the invention was to obtain composite bone implants containing hydroxyapatite and fibroin with a higher mechanical strength than previously known.
  • a method of manufacturing implants which includes a step of preparation a raw material (consisting of the synthetic hydroxyapatite and fibroin), and a step of forming the implant from such a raw material by pressing.
  • the method of manufacturing implants according to the invention consists of using the raw material in a powdered form, and in the raw material preparation step a composite powder is produced by simultaneous cryogenic grinding and mixing of fragmented natural silk fibres and powdered synthetic nanometric hydroxyapatite.
  • the proportion of hydroxyapatite in the obtained raw material is from 70% to 95% by weight.
  • a nanometric hydroxyapatite with a particle size of not more than 80 nm is used.
  • the composite powder, obtained by cryogenic mixing and grinding is dried, advantageously at a temperature of not more than 160°C, until the powder has lost at least 2% of the initial weight.
  • cryogenic grinding and mixing is carried out at a temperature no higher than -150°C.
  • the raw material in a form of composite powder is pressed at a pressure of not less than 0.8 GPa and not more than 1.5 GPa.
  • hydroxyapatite is used with a molar ratio of calcium to phosphorus in the range from 1.57 to 1.65.
  • cryogenic grinding and mixing is carried out until a powder with a homogenous appearance is obtained.
  • drying of the composite powder is carried out in a vacuum, after which the powder is purged with an inert gas.
  • the pressing of the composite powder is carried out at a temperature not lower than 20°C and not higher than 160°C.
  • the method of manufacturing a powdered raw material for bone implants according to the invention consists of cryogenic grinding of sections of natural silk fibre with a length not exceeding 20 mm and mixing them with powdered synthetic nanometric hydroxyapatite in an amount from 70% to 95% by weight.
  • a nanometric hydroxyapatite with a particle size of not more than 80 nm is used.
  • the composite powder obtained by cryogenic grinding and mixing, is dried, preferably at a temperature not higher than 160°C, until the powder has lost at least 2% of the initial mass.
  • cryogenic grinding and mixing is carried out at a temperature no higher than -150°C.
  • hydroxyapatite is used with a molar ratio of calcium to phosphorus in the range of 1.57 to 1.65.
  • a cryogenic grinding and mixing are carried out until a powder with a homogenous appearance is obtained.
  • the drying of the composite powder is carried out in a vacuum, after which the powder is purged with an inert gas.
  • the powdered raw material according to the invention contains a synthetic hydroxyapatite and fibroin and is characterized by containing from 70% to 95% by weight of hydroxyapatite with a particle size of not more than 80 nm and a molar ratio of calcium to phosphorus in the range from 1.57 up to 1.65.
  • the raw material according to the invention it contains fibroin in the form of natural silk fibres.
  • the fibroin fibres have a length of not more than 1000 pm and a diameter of not more than 20 pm. In another variant of the raw material according to the invention at least 50% of the fibroin fibre surface is coated with hydroxyapatite particles adhering to it.
  • the implant according to the invention consisting of a homogeneous mixture of synthetic hydroxyapatite and fibroin, has a content of 70% to 95% by weight of nanometric hydroxyapatite with a particle size of not more than 80 nm and a molar ratio of calcium to phosphorus from 1.57 to 1.65, Young's modulus in the range from 7.5 to 9.5 GPa, total porosity in the range from 10 to 20%, bending strength not less than 30 MPa and compressive strength not less than 100 MPa.
  • the implant according to the invention consists fibroin in the form of a component of a natural silk fibre.
  • the fibroin fibres have a length of not more than 1000 pm and a diameter of not more than 20 pm.
  • the implant according to the invention has an isotropic micro- pattern in areas of 500 pm x 500 pm x 500 pm.
  • the invention presents a very simple way for obtaining bone implants containing hydroxyapatite and fibroin with much higher strength parameters than those previously known. This is achieved without the chemical reaction stage and without introducing other substances into the composite. Furthermore, the implants according to the invention have fibrous structures that improve the biocom- patibility of the implant.
  • Fig.1 presents an SEM image of the implant from the first example
  • Fig.2 presents an SEM image of the implant from the second example
  • Fig.3 presents an SEM image of the implant from the third example
  • Fig.4 presents an SEM image of the implant from the fourth example.
  • Fig.5A, Fig.5B, Fig.5C i Fig.5D present microtomographic images of the implant section from the first example.
  • Fig.6 and Fig.7 show, in two different magnifications, the SEM images of the composite powder from which the implant of the first and third examples has been made
  • Fig.8 and Fig.9 show the composite powder of the second and fourth examples
  • the selected hydroxyapatite powder was characterized by a particle size ranging from 7 to 9 nm, a specific surface area ranging from 225 to 275 m 2 /g, a density of 2.87 g/cm 3 and a molar ratio of calcium to phosphorus from 1.57 to 1.65.
  • the hydroxyapatite powder and cut silk fibres were placed in a container of a cryogenic mill type 6775, SPOEX SamplePrep. The mill grinds substances in a heat-conducting container immersed in liquid nitrogen. In the container, apart from the given substance, a ferromagnetic grinding impactor is placed, which is moved inside the container by a variable magnetic field.
  • cryogenic mill In the cryogenic mill described above, a temperature of -190°C was generated and the frequency of impacts of the impactor was set at 2/s. After 15 minutes of cooling the contents of the container, the mill was turned on three times for one minute, with six-minute intervals for cooling the contents of the container to the starting temperature between the subsequent periods of operation.
  • the parameters of the cryogenic treatment of the described components were selected for to obtain a powder with a homogeneous appearance when assessed by the unaided eye.
  • the two-component (composite) powder thus obtained was kept for three hours in a vacuum oven at 100°C. The degree of powder dryness was evaluated using STA thermal analysis.
  • Dried composite powder a raw material for the production of composite implants, was cast into a matrix, with rectilinear walls measuring 20 mm x 4 mm, and a matching stamp, in which temperature of 80°C was maintained.
  • the composite powder was left for 10 minutes to equilibrate the temperatures, after which the stamp was pressed in order obtain a pressure of 1 GPa in the matrix, which was maintained for one minute.
  • the matrix was disassembled to extract the finished implant.
  • the material of the obtained implant had homogeneous fibres evenly distributed in the hydroxyapatite matrix, a total porosity of 14.1%, a bending strength of 86 MPa and a compressive strength of 276 MPa.
  • Fig.5A shows a three- dimensional model of the distribution of fibroin fibres in a 500 ⁇ x 500 ⁇ x 1000 m rectangular breakthrough of the implant.
  • Fig.5B shows a tomographic image of the implants microstructure in the XY plane of Fig.5A
  • Fig.5C shows a tomographic image of the implants microstructure in the XZ plane of Fig,5A
  • Fig.5D shows an image of the implants microstructure in the YZ plane of Fig.5A. None of these three figures reveal the directional orientation of silk fibres.
  • Example 2 shows a tomographic image of the implants microstructure in the XY plane of Fig.5A
  • Fig.5C shows a tomographic image of the implants microstructure in the XZ plane of Fig,5A
  • Fig.5D shows an image of the implants microstructure in the YZ plane of Fig.5A. None of these three figures reveal the directional orientation of silk fibres.
  • Example 2 shows a tomographic image of the implants microstructure in the XY plane of Fig.5A
  • Fig.5C shows a tomographic image of the implants microstructure in the
  • Fig.8 shows a SEM image of the powder in which, at 500x magnification, short pieces of fibres closely covered with a hydroxyapatite layer can be seen
  • Fig.9 shows a SEM image of the same powder in which, at 10000x magnification, a single silk fibre is visible with closely adhering hydroxyapatite.
  • the powder was pressed in the same way as before, but the matrix was not heated.
  • the material of the obtained implant, shown in Fig.2 had silk fibres evenly distributed in the hydroxyapatite matrix, total porosity of 15.3%, and a bending strength of 32 MPa.
  • Fig.2 shows a SEM image in which implants breakthrough is visible at a magnification of 5000x, as a result of breakage the fibre has been broken, which confirms the good adhesion of hydroxyapatite to silk fibres.
  • an implant containing 85% by weight of hydroxyapatite and 15% silk was subjected to cold pressing under pressure of 1 GPa.
  • This implant has been made of the powdered composite raw material described in the first example.
  • Fig.3 shows in the SEM image, at 1000x magnification, a homogenous distribution of the silk fibres embedded in the hydroxyapatite matrix of this implant.
  • the material of the obtained implant was characterized by a total porosity of 16.8% and a bending strength of 56 MPa.
  • FIG.3 is an 1000x magnified SEM image of this implant structure. The image shows silk fibres in a morphologically unchanged form and adhering well to the hydroxyapatite matrix.
  • the obtained implant was characterized by a total porosity of 11.3% and a bending strength of 46 MPa.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Molecular Biology (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials Engineering (AREA)
  • Inorganic Chemistry (AREA)
  • Composite Materials (AREA)
  • Urology & Nephrology (AREA)
  • Zoology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Le procédé de production d'implant comprend une étape de préparation d'une matière première sous forme pulvérulente et une étape de formation de l'implant par pression. Dans l'étape de préparation de matière, des fragments de la fibre de soie naturelle sont broyés de manière cryogénique et mélangés avec de l'hydroxyapatite nanométrique synthétique en poudre. La proportion d'hydroxyapatite dans le mélange est comprise entre 70 % et 95 % en masse. La poudre composite, qui est la matière première pour la formation des implants, contient de l'hydroxyapatite de granulométrie ne dépassant pas 80 nm et un rapport molaire de calcium sur le phosphore dans l'hydroxyapatite compris dans l'intervalle allant de 1,57 à 1,67. L'implant osseux composite contient de la fibroïne et entre 70 % et 95 % en masse d'hydroxyapatite de granulométrie ne dépassant pas 80 nm, et un rapport molaire de calcium sur le phosphore comprise entre 1,57 et 1,65. Le module d'Young du matériau d'implant est situé dans l'intervalle allant de 7,5 à 9,5 GPa, sa porosité totale est comprise entre 10 et 20 %. La résistance à la flexion d'un tel implant est d'au moins 30 MPa, et sa résistance à la compression est d'au moins 100 MPa.
PCT/PL2018/050008 2017-03-07 2018-03-05 Procédé de fabrication d'implants osseux composites, procédé de fabrication de matière première en poudre pour de tels implants, ladite matière première en poudre et ledit implant osseux WO2018164594A1 (fr)

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Application Number Priority Date Filing Date Title
PL420762A PL244595B1 (pl) 2017-03-07 2017-03-07 Sposób wytwarzania kompozytowych implantów kostnych, sposób wytwarzania sproszkowanego surowca na kompozytowe implanty kostne, sproszkowany surowiec na implanty kostne i kompozytowy implant kostny
PLP.420762 2017-03-07

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111849013A (zh) * 2020-07-14 2020-10-30 重庆医科大学附属口腔医院 一种纳米羟基磷灰石-丝素蛋白矿化支架及其制备方法和用途
CN116262147A (zh) * 2021-12-15 2023-06-16 西湖大学 丝蛋白/生物陶瓷复合材料及其制备方法和应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014003588A1 (fr) * 2012-06-27 2014-01-03 Instytut Wysokich Cisnien Polskiej Akademii Nauk Procédé de fabrication d'implants osseux, et implant osseux
WO2015009246A1 (fr) * 2013-07-19 2015-01-22 National University Of Singapore Dispositif d'augmentation d'interface tissulaire pour reconstruction ligamentaire/tendineuse

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014003588A1 (fr) * 2012-06-27 2014-01-03 Instytut Wysokich Cisnien Polskiej Akademii Nauk Procédé de fabrication d'implants osseux, et implant osseux
WO2015009246A1 (fr) * 2013-07-19 2015-01-22 National University Of Singapore Dispositif d'augmentation d'interface tissulaire pour reconstruction ligamentaire/tendineuse

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LI WANG ET AL: "High-affinity integration of hydroxyapatite nanoparticles with chemically modified silk fibroin", JOURNAL OF NANOPARTICLE RESEARCH ; AN INTERDISCIPLINARY FORUM FOR NANOSCALE SCIENCE AND TECHNOLOGY, KLUWER ACADEMIC PUBLISHERS, DO, vol. 9, no. 5, 18 October 2006 (2006-10-18), pages 919 - 929, XP019506672, ISSN: 1572-896X *
WANG ET AL: "Preparation and physicochemical properties of a novel hydroxyapatite/chitosan-silk fibroin composite", CARBOHYDRATE POLYM, APPLIED SCIENCE PUBLISHERS, LTD. BARKING, GB, vol. 68, no. 4, 16 March 2007 (2007-03-16), pages 740 - 745, XP005938831, ISSN: 0144-8617, DOI: 10.1016/J.CARBPOL.2006.08.010 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111849013A (zh) * 2020-07-14 2020-10-30 重庆医科大学附属口腔医院 一种纳米羟基磷灰石-丝素蛋白矿化支架及其制备方法和用途
CN116262147A (zh) * 2021-12-15 2023-06-16 西湖大学 丝蛋白/生物陶瓷复合材料及其制备方法和应用

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