Silk apatite composites from electrospun fibers

Human bone is a three-dimensional composite structure consisting of inorganic apatite crystals and organic collagen fibers. An attractive strategy for fabricating mimics of these types of composite biomaterials is to selectively grow apatite on polymers with control of structure, mechanical properties, and function. In the present study, silk/apatite composites were prepared by growing apatite on functionalized nanodiameter silk fibroin fibers prepared by electrospinning. The functionalized fibers were spun from an aqueous solution of silk/polyethylene oxide (PEO) (78/22 wt/wt) containing poly(L-aspartate) (poly-Asp), which was introduced as an analogue of noncollageous proteins normally found in bone. Silk fibroin associated with the acidic poly-Asp and acted as template for mineralization. Apatite mineral growth occurred preferentially along the longitudinal direction of the fibers, a feature that was not present in the absence of the combination of components at appropriate concentrations. Energy dispersive spectroscopy and x-ray diffraction confirmed that the mineral deposits were apatite. The results suggest that this approach can be used to form structures with potential utility for bone-related biomaterials based on the ability to control the interface wherein nucleation and crystal growth occur on the silk fibroin. With this level of inorganic–organic control, coupled with the unique mechanical properties, slow rates of biodegradation, and polymorphic features of this type of proteins, new opportunities emerge for utility of biomaterials.

[1]  Anna Tampieri,et al.  Biologically inspired growth of hydroxyapatite nanocrystals inside self-assembled collagen fibers , 2003 .

[2]  J. Tanaka,et al.  Apatite formation on organic monolayers in simulated body environment. , 2000, Journal of biomedical materials research.

[3]  D. Kaplan,et al.  Biomaterial films of Bombyx mori silk fibroin with poly(ethylene oxide). , 2004, Biomacromolecules.

[4]  Ung-Jin Kim,et al.  Three-dimensional aqueous-derived biomaterial scaffolds from silk fibroin. , 2005, Biomaterials.

[5]  David L Kaplan,et al.  Electrospinning Bombyx mori silk with poly(ethylene oxide). , 2002, Biomacromolecules.

[6]  David L Kaplan,et al.  Silk-based biomaterials. , 2003, Biomaterials.

[7]  C. Buchko,et al.  Surface characterization of porous, biocompatible protein polymer thin films. , 2001, Biomaterials.

[8]  D. Kaplan,et al.  Biomimetic composites via molecular scale self-assembly and biomineralization , 2003 .

[9]  H. M. Kim,et al.  Thin film of low-crystalline calcium phosphate apatite formed at low temperature. , 2000, Biomaterials.

[10]  David C. Martin,et al.  Processing and microstructural characterization of porous biocompatible protein polymer thin films , 1999 .

[11]  M. Tanihara,et al.  Coating of an apatite layer on polyamide films containing sulfonic groups by a biomimetic process. , 2004, Biomaterials.

[12]  Z. Shao,et al.  Regenerated Bombyx silk solutions studied with rheometry and FTIR , 2001 .

[13]  M. Akashi,et al.  Preparation and characterization of apatite deposited on silk fabric using an alternate soaking process. , 2000, Journal of biomedical materials research.

[14]  David L Kaplan,et al.  Human bone marrow stromal cell responses on electrospun silk fibroin mats. , 2004, Biomaterials.

[15]  Andreas Greiner,et al.  Electrospun nanofibers: Internal structure and intrinsic orientation , 2003 .

[16]  David L Kaplan,et al.  Macrophage responses to silk. , 2003, Biomaterials.

[17]  David G Simpson,et al.  Electrospinning of collagen nanofibers. , 2002, Biomacromolecules.

[18]  Y. Ikada,et al.  Histologic and mechanical evaluation for bone bonding of polymer surfaces grafted with a phosphate-containing polymer. , 1997, Journal of biomedical materials research.

[19]  Younan Xia,et al.  Electrospinning Nanofibers as Uniaxially Aligned Arrays and Layer‐by‐Layer Stacked Films , 2004 .

[20]  T. Yamamuro,et al.  Apatite coated on organic polymers by biomimetic process: improvement in its adhesion to substrate by glow-discharge treatment. , 1995, Journal of biomedical materials research.

[21]  A. Wan,et al.  Preparation of a chitin-apatite composite by in situ precipitation onto porous chitin scaffolds. , 1998, Journal of biomedical materials research.

[22]  Y Ikada,et al.  Deposition of a hydroxyapatite thin layer onto a polymer surface carrying grafted phosphate polymer chains. , 1996, Journal of biomedical materials research.

[23]  Mingzhong Li,et al.  Controlling molecular conformation of regenerated wild silk fibroin by aqueous ethanol treatment , 2003 .

[24]  J. Vacanti,et al.  A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. , 2003, Biomaterials.

[25]  Huajian Gao,et al.  Materials become insensitive to flaws at nanoscale: Lessons from nature , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Elliot L. Chaikof,et al.  Generation of Synthetic Elastin-Mimetic Small Diameter Fibers and Fiber Networks , 2000 .

[27]  Y. Ikada,et al.  In vitro hydroxyapatite deposition onto a film surface-grated with organophosphate polymer. , 1994, Journal of biomedical materials research.

[28]  N. Sasaki,et al.  X-ray Pole Figure Analysis of Apatite Crystals and Collagen Molecules in Bone , 1997, Calcified Tissue International.

[29]  David L Kaplan,et al.  Porous 3-D scaffolds from regenerated silk fibroin. , 2004, Biomacromolecules.

[30]  David L Kaplan,et al.  Mapping domain structures in silks from insects and spiders related to protein assembly. , 2004, Journal of molecular biology.

[31]  Chikara Ohtsuki,et al.  Deposition of bone-like apatite on silk fiber in a solution that mimics extracellular fluid. , 2003, Journal of biomedical materials research. Part A.

[32]  Hyunmin Kim,et al.  Apatite-forming ability of carboxyl group-containing polymer gels in a simulated body fluid. , 2003, Biomaterials.

[33]  E. Chaikof,et al.  High-resolution analysis of engineered type I collagen nanofibers by electron microscopy. , 2001, Scanning.

[34]  S. Hudson,et al.  Structural characteristics and properties of the regenerated silk fibroin prepared from formic acid. , 2001, International journal of biological macromolecules.

[35]  J. Trouillet,et al.  Osseointegration of macroporous calcium phosphate ceramics having a different chemical composition. , 1993, Biomaterials.

[36]  M Tanahashi,et al.  Surface functional group dependence on apatite formation on self-assembled monolayers in a simulated body fluid. , 1997, Journal of biomedical materials research.

[37]  John Layman,et al.  Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[38]  J D Stitzel,et al.  Arterial Smooth Muscle Cell Proliferation on a Novel Biomimicking, Biodegradable Vascular Graft Scaffold , 2001, Journal of biomaterials applications.

[39]  T. Yamamuro,et al.  Apatite coated on organic polymers by biomimetic process: improvement in its adhesion to substrate by NaOH treatment. , 1994, Journal of applied biomaterials : an official journal of the Society for Biomaterials.

[40]  S. Weiner,et al.  Organization of hydroxyapatite crystals within collagen fibrils , 1986, FEBS letters.

[41]  O. Tretinnikov,et al.  Influence of Casting Temperature on the Near-Surface Structure and Wettability of Cast Silk Fibroin Films , 2001 .

[42]  Holger Schönherr,et al.  Chain Packing in Electro-Spun Poly(ethylene oxide) Visualized by Atomic Force Microscopy , 1996 .

[43]  S. Ichinose,et al.  Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo. , 2001, Biomaterials.

[44]  Karthik Nagapudi,et al.  Engineered collagen–PEO nanofibers and fabrics , 2001, Journal of biomaterials science. Polymer edition.

[45]  J. Tanaka,et al.  Biomimetic configurational arrays of hydroxyapatite nanocrystals on bio-organics. , 2001, Biomaterials.

[46]  M. Akashi,et al.  Apatite coating on hydrophilic polymer-grafted poly(ethylene) films using an alternate soaking process. , 2001, Biomaterials.

[47]  P. Ma,et al.  Porous poly(L-lactic acid)/apatite composites created by biomimetic process. , 1999, Journal of biomedical materials research.

[48]  A. Bigi,et al.  Bonelike apatite growth on hydroxyapatite-gelatin sponges from simulated body fluid. , 2002, Journal of biomedical materials research.

[49]  K. Nakanishi,et al.  Bonelike apatite formation on ethylene-vinyl alcohol copolymer modified with silane coupling agent and calcium silicate solutions. , 2003, Biomaterials.

[50]  H. Fong,et al.  Structure of Poly(ferrocenyldimethylsilane) in Electrospun Nanofibers , 2001 .

[51]  David L Kaplan,et al.  Human bone marrow stromal cell and ligament fibroblast responses on RGD-modified silk fibers. , 2003, Journal of biomedical materials research. Part A.

[52]  P. Fratzl,et al.  Mineralized collagen fibrils: a mechanical model with a staggered arrangement of mineral particles. , 2000, Biophysical journal.

[53]  M. Chance,et al.  Conformation transition kinetics of regenerated Bombyx mori silk fibroin membrane monitored by time-resolved FTIR spectroscopy. , 2001, Biophysical chemistry.

[54]  D H Kohn,et al.  Growth of continuous bonelike mineral within porous poly(lactide-co-glycolide) scaffolds in vitro. , 2000, Journal of biomedical materials research.

[55]  Ivan Martin,et al.  Silk matrix for tissue engineered anterior cruciate ligaments. , 2002, Biomaterials.

[56]  David L. Kaplan,et al.  Mechanism of silk processing in insects and spiders , 2003, Nature.