+

WO2001070293A1 - Matieres composites polymeriques et leur fabrication - Google Patents

Matieres composites polymeriques et leur fabrication Download PDF

Info

Publication number
WO2001070293A1
WO2001070293A1 PCT/GB2001/001177 GB0101177W WO0170293A1 WO 2001070293 A1 WO2001070293 A1 WO 2001070293A1 GB 0101177 W GB0101177 W GB 0101177W WO 0170293 A1 WO0170293 A1 WO 0170293A1
Authority
WO
WIPO (PCT)
Prior art keywords
polymer
collagen
solution
poly
synthetic
Prior art date
Application number
PCT/GB2001/001177
Other languages
English (en)
Inventor
Allan Gerald Arthur Coombes
Sandra Downes
Martin Griffin
Original Assignee
The University Of Nottingham
The Nottingham Trent University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The University Of Nottingham, The Nottingham Trent University filed Critical The University Of Nottingham
Priority to AU40878/01A priority Critical patent/AU4087801A/en
Publication of WO2001070293A1 publication Critical patent/WO2001070293A1/fr

Links

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
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • 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
    • A61L27/56—Porous materials, e.g. foams or sponges

Definitions

  • This invention relates to composite polymeric materials of particular utility in medical and biological applications including tissue engineering.
  • Tissue engineering continues to attract considerable and growing interest from researchers across a wide range of disciplines because of the potential for providing improved biomaterials for hard and soft tissue repair and implantable devices for mimicing the function of organs such as the liver and pancreas.
  • Production of scaffolds to support and encourage cell development and correct function depends critically on the design, physico-chemical nature and the material architecture (micro/macroporosity).
  • Autograft and banked bone are the best materials for repairing hard tissue but there are problems of supply and spread of infection respectively.
  • Collagen is currently the most popular material for scaffold production in connective tissue repair but is difficult to formulate reproducibly. Concerns also exist over the immune response to implanted collagen.
  • GAGs glycosaminoglycans
  • fibronectin eg chondroitin-6-sulphate
  • hyaluronate a bioactive material
  • Such materials have also been formulated to incorporate RGD- containing peptides (the integrin-mediated cell attachment domain found in many extracellular matrix proteins, RGD- being arginine-glycine-aspartine-), the aim being to promote cell attachment and thus wound healing (Grzesiak et al, 1997).
  • Hyaluronic acid is a polysaccharide made up of molecules of N-acetylglucosamine and D-glucuronic acid. HA is involved in cell migration, adhesion, aggregation, proliferation and cell function and has been widely investigated for modulating cell-biomaterial interactions. HA dissolves on contact with biological fluids. As a result, thermal crosslinking has been applied to blends of HA and carboxyl-containing polymers such as polyacrylamide (PAA) to create stabilising, intermolecular bridges.
  • PPA polyacrylamide
  • Natural polymers offer advantages of good biocompatibility but their use as biomaterials is often limited by their poor mechanical properties. The need to preserve biological properties also complicates their formulation into biomaterials. Native collagen, for example, possesses good tensile properties but these are reduced by the chemical processes used to isolate the material which results in non-fibrous materials. Biodegradation, post-implantation, also results in rapid deterioration of structural and biological properties.
  • IPNs interpenetrating polymer networks
  • composites of collagen with synthetic materials have been widely investigated in attempts to overcome the deficiencies of collagen as a biomaterial.
  • Collagen matrices (used for repair of connective tissue such as skin) are generally chemically crosslinked (eg using glutaraldehyde) to improve biological stability, ease of handling and mechanical properties (Grzesiak et al, 1997). This process can cause problems of toxicity due to residual unreacted or partially reacted crosslinking agent.
  • Improved dermal matrix has been developed by culturing human fibroblasts on biodegradable synthetic polymer mesh produced from polyglactin 9-10 (Vicryl).
  • the material has been termed Dermagraft by the manufacturers (Advanced Tissue Sciences, La Jolla, California).
  • the fibroblasts secrete proteins and glycoproteins as they grow in the Vicryl mesh, forming an extracellular matrix which fills the mesh interstices.
  • Composite structures consisting of Dermagraft and overlying meshed skin grafts are expected to be resistant to wound proteases and thus allow more efficient wound closure.
  • Biocomposites comprising synthetic polymers such as poly(vinyl alcohol) (PVA) or poly(2- hydroxyethylmethacrylate) [poly(HEMA)] and natural polymers such as collagen and gelatin have been widely investigated with the aim of exploiting the advantageous properties of each component and compensating for less desirable characteristics (Giusti et al, 1993(a)). For example, the poor cell adhesion normally associated with poly(HEMA) has been mitigated by blending the synthetic polymer with collagen (Santin et al, 1996). This approach subsequently enables application of the biocomposite for tissue engineering or biological scaffolding where growing cells are supported during wound repair to encourage integration of host tissue and implant.
  • PVA poly(vinyl alcohol)
  • poly(HEMA) poly(2- hydroxyethylmethacrylate)
  • Biocomposites of synthetic polymers and natural polymers benefit potentially from the wide range of mechanical properties and processing techniques applicable to synthetic polymers. These advantages may be augmented by the biocompatibility of natural polymers and the wide diversity of biological reactions which may be induced by contact between the natural polymer and host cells and tissue.
  • Hydrogels are three dimensional polymeric networks generally stabilised by covalent crosslinking and weak cohesive forces, particularly hydrogen bonds. These networks imbibe large quantities of water or organic liquids without dissolution. In turn, the large water content imparts a very low interfacial tension with biological fluids. This feature, along with high permeability to small molecules (such as tissue metabolites) and their viscoelastic nature makes hydrogels behave similarly to biological tissues. As a result, they have been used as biomaterials in a wide variety of biomedical applications such as opthalmology, drug delivery and orthopaedics.
  • IPNs may be described as multi-phase materials wherein each phase is independent, continuous and contacts all portions of the sample space. IPNs are often manufactured by a sequential method involving swelling of a pre-synthesised network in a solution of the second polymer to be crosslinked. A high porosity of the first network is desirable to achieve satisfactory loading or impregnation of the second polymer.
  • IPNs based on poly(HEMA) and gelatin have been described (Santin et al, 1996). They were prepared by impregnating freeze-dried, crosslinked, poly(HEMA) hydrogel films (0.5-3.0 mm thick) with gelatin solution. The gelatin phase was subsequently crosslinked using glutaraldehyde.
  • IPNs of fibrin and polyurethane have been prepared by spraying a suspension of the natural and synthetic polymers simultaneously with water onto a substrate.
  • the fibrinogen was subsequently covalently crosslinked using thrombin, factor XIII and calcium ions (Giusti et al 1993(a)).
  • PVA-collagen blends may also be produced by repeated freeze-thawing of a solution containing both polymers (Giusti et al 1993(b)).
  • the freeze-thaw process results in the formation of crystallites of PVA which act as crosslinking sites between polymer chains and gives rise to hydrogel formation.
  • the hydrogel is capable of entrapping the natural polymer (eg collagen) within the PVA network.
  • PVA is not biodegradable and its use for implant manufacture has been associated with adverse reactions in vivo.
  • a method for the preparation of a polymeric composite material comprises the steps of a) forming a porous body of a first polymer; b) impregnating said porous body with a solution of a second polymer; and c) causing or allowing solvent to evaporate from said body.
  • one of the first and second polymers is a natural polymer or a synthetic analogue thereof and the other is a synthetic polymer. Most preferably, it is the first polymer which is the natural polymer or synthetic analogue and the second polymer is synthetic.
  • the porous body of first polymer is preferably prepared by forming a solution, eg an aqueous solution, of the first polymer and lyophilising that solution.
  • a solution eg an aqueous solution
  • the body prepared in this manner will commonly have the form of a porous mat.
  • the method of biocomposite manufacture avoids chemical, thermal or irradiation- induced stabilisation of the natural polymer, thereby eliminating structural damage or modification due to crosslinking.
  • the natural polymer phase is expected to be stabilised due to localised coating by the synthetic polymer phase.
  • the synthetic polymer component may be produced from biodegradable polymers such as polylactide which potentially allows complete replacement of the implant by repair tissue.
  • the synthetic polymer is not crosslinked during biocomposite manufacture to confer structural stability, which eliminates problems of toxicity due to residual crosslinking agent.
  • the solvent used to form the second polymer solution for impregnation of the porous body may be any suitable solvent in which the second polymer is sufficiently soluble and which is sufficiently volatile subsequently to be removed by evaporation or sublimation.
  • the structural properties of the biocomposite enables applications for bone repair where some load bearing role can be expected and is indeed desirable to expose the repair tissue to stress fields for optimal development (the bone remodelling phase of bone repair).
  • Variation in exposure/presentation of the natural polymer can be achieved by controlling process conditions such as concentration and volume of the polymer solutions.
  • This facility should also be useful for controlling the delivery of bioactive factors (eg growth factors) incorporated in the biocomposite.
  • the open porous structure of the biocomposites having pore sizes ranging from 50-1 OO ⁇ m, is expected to facilitate cell ingrowth and good integration of the biocomposite with the host tissue.
  • Specific areas of use could include implants for bone and cartilage repair, bone graft substitutes, cardiovascular devices, nerve guides, connective tissue repair and artificial skin grafts, wound and burn dressings and controlled release systems for delivery of bioactive materials such as steroids, oligonucleotides and DNA, and growth factors.
  • biocomposites produced by the method of the invention could find application as bioactive constructs for tissue engineering where controlled release of growth factors encourages and guides tissue repair.
  • the biocomposites of the invention may be useful as a replacement for allogeneic bone obtained from bone banks.
  • the method for preparing the biocomposites is expected to be useful for coating glass and plasticware for cell culture.
  • Applications in drug delivery such as transdermal administration of hormones via patch-type devices are also envisaged.
  • Natural polymers envisaged as being useful in the method include gelatin and extra cellular matrix proteins (collagen, elastin, laminin), cell adhesion proteins (such as fibronectin, vitronectin, vinculin, fibrinogen), polysaccharides (eg hyaluronic acid, heparin), glycosaminoglycans (such as chondroitin-4-sulphate) and combinations of natural polymers or natural polymer-synthetic polymer conjugates.
  • the presently preferred natural polymer is collagen.
  • Synthetic analogues of natural polymers such as silk-like and elastin-like protein polymers (Capello, 1997) may be substituted in total or in part for the natural polymer.
  • Heparin-like synthetic polymers (Miggoney et al, 1988) are further examples of synthetic analogues of natural polymers.
  • Synthetic polymers include poly( ⁇ -hydroxy acid) such as polylactide, poly(DL lactide co-glycolide), poly( ⁇ -caprolactone), polyorthoesters, polyphosphazines, hyaluronic acid esters, polyanhydrides, copolymers of the above polymers and blends.
  • poly( ⁇ -hydroxy acid) such as polylactide, poly(DL lactide co-glycolide), poly( ⁇ -caprolactone), polyorthoesters, polyphosphazines, hyaluronic acid esters, polyanhydrides, copolymers of the above polymers and blends.
  • Suitable polymers may thus be members of the class of polyesters formed by ring- opening polymerisation. Precursors to such polymers may thus have the generic formula
  • R represents an optionally substituted alkylene chain, eg a chain (CH 2 ) n in which n is an integer of from about 4 to 10.
  • n is 5.
  • R 1 and R 2 which may be the same or different, represent optionally substituted lower alkyl groups, ie alkyl groups of 1 to 6 carbon atoms. In one preferred case, at least one, and preferably both, of R 1 and R 2 represents methyl.
  • the presently preferred synthetic polymer is poly( ⁇ -caprolactone), a biodegradable polymer from the same family of poly ( ⁇ -hydroxy acids) as polylactide (PLA) and polyglycolide (PGA).
  • PCL Polycaprolactone
  • the characteristics of the composite material produced in accordance with the invention will generally depend on factors such as the first polymer : second polymer weight ratio. That ratio may vary widely but for many applications a first polymer : second polymer (eg collagen : PCL) ratio of 1 :40 or less (eg 1 :8 or 1 :4) is preferred. It is found that biocomposites having such a composition may have a highly porous morphology which would be expected to facilitate ingress of, for instance, enzyme solutions, and a high degree of interaction with proteins or cells contacting the surface.
  • a first polymer : second polymer eg collagen : PCL
  • biocomposites having such a composition may have a highly porous morphology which would be expected to facilitate ingress of, for instance, enzyme solutions, and a high degree of interaction with proteins or cells contacting the surface.
  • Collagen:PCL biocomposites were produced by impregnation of lyophilised collagen mats using a solution of PCL in dichloromethane (DCM), followed by solvent evaporation. The process stages are described in detail below.
  • DCM dichloromethane
  • Collagen solutions (0.25, 0.5 and 1% w/v) were prepared by dissolving Type 1 , acid-soluble collagen from calf skin (Sigma C-3511) in 1 % acetic acid. The pH was adjusted to 2.9 using 0.1M NaOH and dissolution was facilitated by stirring with a magnetic stirrer overnight at room temperature.
  • the extent of exposure of collagen at the surface of collagen:PCL biocomposites can be expected to exert a major influence on the interaction of cells with the biomaterial through, for example, binding of fibronectin or related cell adhesion proteins.
  • controlled changes in coating efficiency may also be used to influence the pattern of release or presentation of co-factors such as peptide fragments or growth factors.
  • SEM analysis clearly demonstrated the changes in morphology which could be achieved by variation of processing parameters such as collagen: PCL ratio.
  • a collagenase digestion assay was applied to the collagen:PCL biocomposites to provide further insights regarding collagen presentation/exposure.
  • Collagen:PCL biocomposites were prepared in 7ml squat vials by freeze drying 2ml, 0.25%, collagen solution and impregnating the dried mat with 2ml PCL solution. The materials were washed in PBS for 4 hours and left immersed in fresh PBS for 48 hours prior to testing for exposed collagen.
  • Collagen:PCL biocomposites were also prepared in 4ml glass shell vials by freeze drying 0.5ml, 0.25% collagen solution and impregnating the dried mat with 0.5 ml of PCL solution. The materials were washed in PBS and left immersed in fresh PBS overnight.
  • Samples were cut from the mats and analysed for exposed/presented collagen using a collagenase digestion technique.
  • the BCA total protein assay (Sigma) was used to measure the amount of collagen digested from collagen:PCL biocomposites after incubation in enzyme solution at 37°C.
  • Collagen calibration samples (0.5-2.0mg) were also added to 2ml of digestion medium (0.1 mg/ml collagenase solution in HBSS) and retained at 37°C in 20ml glass vials until dissolved (2.5-3.0 hours). Test and calibration samples were allowed to cool to room temperature and tested immediately using the BCA total protein assay.
  • BCA reagent (2ml bicinchoninic acid solution, 40 ⁇ l copper II sulphate) was added to 100 ⁇ l aliquots of the digestion solution and retained in a water bath at 37°C for approximately 30 minutes.
  • the absorbance at 562nm was recorded using a UV spectrophotometer (Unicam UV/VIS Spectrometer, UV4) and used to construct a calibration curve.
  • Collagen solution (0.25% w/v) was prepared by dissolution in 1 % acetic acid adjusted to pH 2.7 using 0.1 M NaOH.
  • the collagen solution was adjusted to a pH of 7.4 using 1 M NaOH followed by O.IM NaOH.
  • the gels were frozen by holding at -80°C for 1-2 hours prior to freeze- drying, solution impregnation and solvent evaporation as described in Example 1.
  • Collagen solution (0.25% w/v) was prepared by dissolution in 1 % acetic acid adjusted to pH 2.7 using 0.1 M NaOH.
  • Hyaluronic acid is a natural glycosaminoglycan (GAG) widely distributed in animal tissues and is also found in the synovial fluid and the vitreous and aqueous humors of the eye.
  • GAG glycosaminoglycan
  • Dermatan and chondroitin sulphate are natural sulphated glycosaminoglycans.
  • GAGs are found in connective tissues at concentrations of less than 10% by weight of the fibrous proteins. They form porous hydrated gels and GAG chains fill most of the extracellular matrix space, providing mechanical support to tissues, while still allowing diffusion of molecules, and cell migration.
  • Collagen/GAG/PCL biocomposites were prepared with collagen/CHS0 4 ratios of 1/1(50% GAG), 4/1(20% GAG), 8/1 (11%) and 16/1(6%). Ch 6 SO4 does not bind to reconstituted collagen under physiological conditions (Hanthamrongwit et al, 1986). Therefore, collagen/ChSO 4 matrices were prepared at 3 different pH values in an attempt to promote collagen/GAG interaction and complexation and to investigate the effect on cell-biocomposite interaction.
  • Chondroitin sulphate A (from bovine trachea, approx, 70%, balance is chondroitin sulphate C) was obtained from Sigma (C-8529).
  • Hyaluronic acid from bovine vitreous humor was also obtained from Sigma (H-7630). 3.2.1 20% ChSQ 4 , system, pH 2.7
  • a turbid suspension of gel/precipitates was obtained at pH 2.7.
  • the suspension was homogenised for 2 minutes using a Silverson homogeniser fitted with a mini-micro mixing head to reduce the size of the precipitates and improve their dispersion.
  • a second suspension was stirred with a magnetic stirrer for 1 hour for comparison with and as an alternative to homogenisation.
  • Collagen solution (0.5% w/v) in 1% acetic acid (pH 2.7) was added to an equal volume of ChSO 4 solution in water (0.5%) to produce a 1 :1 blend of collagen and GAG.
  • Collagen solution (0.5% w/v) in 1% acetic acid (pH 2.7) was added to an equal volume of ChSO 4 solution in water (0.5%) to produce a 1 :1 blend of collagen and GAG.
  • the precipitate obtained was reduced to smaller scale precipitates by adjusting the pH of the medium to 3.9 using 1M NaOH.
  • the suspension was homogenised for 2 minutes using a Silverson homogeniser fitted with a mini-micro mixing head to improve dispersion.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Materials Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Composite Materials (AREA)
  • Dispersion Chemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un procédé de préparation d'une matière composite polymérique consistant (a) à former un corps poreux à base d'un premier polymère, (b) à imprégner ledit corps poreux avec une solution d'un second polymère, et (c) à provoquer ou permettre une évaporation de solvant à partir de ce corps poreux. Le premier polymère est de préférence un polymère naturel, tel que le collagène, le second polymère étant de préférence un polymère synthétique, et notamment un polymère choisi dans le groupe constitué par un poly(α-hydroxy acide), tel qu'un polylactide, un poly(DL lactide co-glycolide), une poly(ε-caprolactone), des polyorthoesters, des polyphosphazines, des esters d'acide hyaluronique, des polyanhydrides, des copolymères de ces polymères et des mélanges desdits composés.
PCT/GB2001/001177 2000-03-18 2001-03-19 Matieres composites polymeriques et leur fabrication WO2001070293A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU40878/01A AU4087801A (en) 2000-03-18 2001-03-19 Polymeric composite materials and their manufacture

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0006439A GB0006439D0 (en) 2000-03-18 2000-03-18 Polymeric composite materials and their manufacture
GB0006439.4 2000-03-18

Publications (1)

Publication Number Publication Date
WO2001070293A1 true WO2001070293A1 (fr) 2001-09-27

Family

ID=9887807

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2001/001177 WO2001070293A1 (fr) 2000-03-18 2001-03-19 Matieres composites polymeriques et leur fabrication

Country Status (3)

Country Link
AU (1) AU4087801A (fr)
GB (1) GB0006439D0 (fr)
WO (1) WO2001070293A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006104901A3 (fr) * 2005-03-28 2007-07-05 Univ Florida Materiaux et procedes d'amelioration de l'ingenierie tissulaire
US7351423B2 (en) 2004-09-01 2008-04-01 Depuy Spine, Inc. Musculo-skeletal implant having a bioactive gradient
US20080097605A1 (en) * 2004-12-15 2008-04-24 Andrea Pastorello Biocompatible Material and Prosthetic Device Made Thereof for the Replacement, Repair and Regeneration of Meniscus
WO2009045176A1 (fr) * 2007-10-03 2009-04-09 Bio-Scaffold International Pte Ltd Procédé de fabrication d'échafaudage pour des applications tissulaires et osseuses
US7569233B2 (en) 2004-05-04 2009-08-04 Depuy Products, Inc. Hybrid biologic-synthetic bioabsorbable scaffolds
US7595062B2 (en) 2005-07-28 2009-09-29 Depuy Products, Inc. Joint resurfacing orthopaedic implant and associated method
US7871440B2 (en) 2006-12-11 2011-01-18 Depuy Products, Inc. Unitary surgical device and method
US7914808B2 (en) 2001-07-16 2011-03-29 Depuy Products, Inc. Hybrid biologic/synthetic porous extracellular matrix scaffolds
US8025896B2 (en) 2001-07-16 2011-09-27 Depuy Products, Inc. Porous extracellular matrix scaffold and method
CN105343937A (zh) * 2015-11-10 2016-02-24 武汉华一同信生物科技有限公司 一种复合多孔质海绵材料及其制备方法
US9592125B2 (en) 2006-12-22 2017-03-14 Laboratoire Medidom S.A. In situ system for intra-articular chondral and osseous tissue repair
CN114209882A (zh) * 2021-12-27 2022-03-22 长春市儿童医院(吉林省儿童医疗中心长春市儿科医学研究所) 一种银纳米粒-胶原蛋白明胶支架材料及其制备方法
TWI777347B (zh) 2020-12-31 2022-09-11 財團法人工業技術研究院 非纖維形式薄膜與細胞層片
CN117065098A (zh) * 2023-08-28 2023-11-17 山东第一医科大学附属眼科研究所(山东省眼科研究所、山东第一医科大学附属青岛眼科医院) 一种人源生物角膜基质的制备方法和应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3841397A1 (de) * 1988-12-08 1990-06-21 Melzer Wolfgang Poroeser resorbierbarer arzneistofftraeger
JPH0323864A (ja) * 1989-06-20 1991-01-31 Gunze Ltd 生体組織用充填材
EP0784985A1 (fr) * 1994-09-30 1997-07-23 Yamanouchi Pharmaceutical Co. Ltd. Greffon osteoplastique
EP0885617A2 (fr) * 1997-06-21 1998-12-23 MERCK PATENT GmbH Matériau pour implant muni d'une combinaison support-produit actif

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3841397A1 (de) * 1988-12-08 1990-06-21 Melzer Wolfgang Poroeser resorbierbarer arzneistofftraeger
JPH0323864A (ja) * 1989-06-20 1991-01-31 Gunze Ltd 生体組織用充填材
EP0784985A1 (fr) * 1994-09-30 1997-07-23 Yamanouchi Pharmaceutical Co. Ltd. Greffon osteoplastique
EP0885617A2 (fr) * 1997-06-21 1998-12-23 MERCK PATENT GmbH Matériau pour implant muni d'une combinaison support-produit actif

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Section Ch Week 199111, Derwent World Patents Index; Class A96, AN 1991-077288, XP002171233 *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7914808B2 (en) 2001-07-16 2011-03-29 Depuy Products, Inc. Hybrid biologic/synthetic porous extracellular matrix scaffolds
US8025896B2 (en) 2001-07-16 2011-09-27 Depuy Products, Inc. Porous extracellular matrix scaffold and method
US7569233B2 (en) 2004-05-04 2009-08-04 Depuy Products, Inc. Hybrid biologic-synthetic bioabsorbable scaffolds
US7351423B2 (en) 2004-09-01 2008-04-01 Depuy Spine, Inc. Musculo-skeletal implant having a bioactive gradient
US8901202B2 (en) * 2004-12-15 2014-12-02 Luigi Ambrosio Biocompatible material and prosthetic device made thereof for the replacement, repair and regeneration of meniscus
US20080097605A1 (en) * 2004-12-15 2008-04-24 Andrea Pastorello Biocompatible Material and Prosthetic Device Made Thereof for the Replacement, Repair and Regeneration of Meniscus
WO2006104901A3 (fr) * 2005-03-28 2007-07-05 Univ Florida Materiaux et procedes d'amelioration de l'ingenierie tissulaire
US7595062B2 (en) 2005-07-28 2009-09-29 Depuy Products, Inc. Joint resurfacing orthopaedic implant and associated method
US7871440B2 (en) 2006-12-11 2011-01-18 Depuy Products, Inc. Unitary surgical device and method
US9592125B2 (en) 2006-12-22 2017-03-14 Laboratoire Medidom S.A. In situ system for intra-articular chondral and osseous tissue repair
WO2009045176A1 (fr) * 2007-10-03 2009-04-09 Bio-Scaffold International Pte Ltd Procédé de fabrication d'échafaudage pour des applications tissulaires et osseuses
CN105343937A (zh) * 2015-11-10 2016-02-24 武汉华一同信生物科技有限公司 一种复合多孔质海绵材料及其制备方法
CN105343937B (zh) * 2015-11-10 2018-05-29 武汉华一同信生物科技有限公司 一种复合多孔质海绵材料及其制备方法
TWI777347B (zh) 2020-12-31 2022-09-11 財團法人工業技術研究院 非纖維形式薄膜與細胞層片
CN114209882A (zh) * 2021-12-27 2022-03-22 长春市儿童医院(吉林省儿童医疗中心长春市儿科医学研究所) 一种银纳米粒-胶原蛋白明胶支架材料及其制备方法
CN117065098A (zh) * 2023-08-28 2023-11-17 山东第一医科大学附属眼科研究所(山东省眼科研究所、山东第一医科大学附属青岛眼科医院) 一种人源生物角膜基质的制备方法和应用
WO2025044684A1 (fr) * 2023-08-28 2025-03-06 山东第一医科大学附属眼科研究所(山东省眼科研究所、山东第一医科大学附属青岛眼科医院) Procédé de préparation de stroma cornéen biologique humain, et utilisation de stroma cornéen biologique humain

Also Published As

Publication number Publication date
GB0006439D0 (en) 2000-05-10
AU4087801A (en) 2001-10-03

Similar Documents

Publication Publication Date Title
US9555164B2 (en) Method for preparing porous scaffold for tissue engineering
Ma et al. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering
Ma et al. Enhanced biological stability of collagen porous scaffolds by using amino acids as novel cross-linking bridges
US5645591A (en) Synthetic bone matrix
Davidenko et al. Collagen–hyaluronic acid scaffolds for adipose tissue engineering
EP2543398B1 (fr) Support de cellules et matériau de régénération osseuse
Lin et al. Synthesis and characterization of collagen/hyaluronan/chitosan composite sponges for potential biomedical applications
US8080590B1 (en) Porous polymeric matrices made of natural polymers and synthetic polymers and optionally at least one cation and methods of making
EP0705878B1 (fr) Compositions contenant des polysaccharides polyanioniques et des polymères hydrophobes bioabsorbables
US5939323A (en) Hyaluronan based biodegradable scaffolds for tissue repair
EP0707498B1 (fr) Prothese implantable, trousse et dispositif de fabrication
Lu et al. Cytocompatibility and blood compatibility of multifunctional fibroin/collagen/heparin scaffolds
Zhang et al. Dehydrothermally crosslinked collagen/hydroxyapatite composite for enhanced in vivo bone repair
US20100233267A1 (en) Composite hydrogel
WO2006031196A1 (fr) Composite de matiere de charge biologique poreuse et procede de fabrication correspondant
WO2001070293A1 (fr) Matieres composites polymeriques et leur fabrication
Shi et al. Cell-compatible hydrogels based on a multifunctional crosslinker with tunable stiffness for tissue engineering
US20030100739A1 (en) Method for producing cross-linked hyaluronic acid-protein bio-composites
Vu et al. Fabrication of in situ crosslinking hydrogels based on oxidized alginate/N, O-carboxymethyl chitosan/β-tricalcium phosphate for bone regeneration
JP3521226B2 (ja) 架橋複合生体材料
Sah et al. Eggshell membrane protein modified silk fibroin-poly vinyl alcohol scaffold for bone tissue engineering: in vitro and in vivo study
Chandy et al. The development of porous alginate/elastin/PEG composite matrix for cardiovascular engineering
Liu et al. Porous poly (DL-lactic acid) modified chitosan-gelatin scaffolds for tissue engineering
Yang et al. Preparation and characterization of collagen-GAGS bioactive matrices for tissue engineering
CN114652896A (zh) 一种高细胞亲和性多糖-活性蛋白/多肽基活性水凝胶微球制备方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载