Natural‐Based Nanocomposites for Bone Tissue Engineering and Regenerative Medicine: A Review

Tissue engineering and regenerative medicine has been providing exciting technologies for the development of functional substitutes aimed to repair and regenerate damaged tissues and organs. Inspired by the hierarchical nature of bone, nanostructured biomaterials are gaining a singular attention for tissue engineering, owing their ability to promote cell adhesion and proliferation, and hence new bone growth, compared with conventional microsized materials. Of particular interest are nanocomposites involving biopolymeric matrices and bioactive nanosized fillers. Biodegradability, high mechanical strength, and osteointegration and formation of ligamentous tissue are properties required for such materials. Biopolymers are advantageous due to their similarities with extracellular matrices, specific degradation rates, and good biological performance. By its turn, calcium phosphates possess favorable osteoconductivity, resorbability, and biocompatibility. Herein, an overview on the available natural polymer/calcium phosphate nanocomposite materials, their design, and properties is presented. Scaffolds, hydrogels, and fibers as biomimetic strategies for tissue engineering, and processing methodologies are described. The specific biological properties of the nanocomposites, as well as their interaction with cells, including the use of bioactive molecules, are highlighted. Nanocomposites in vivo studies using animal models are also reviewed and discussed.

[1]  G. Shi,et al.  Strong composite films with layered structures prepared by casting silk fibroin-graphene oxide hydrogels. , 2013, Nanoscale.

[2]  Rebecca S. Hayden,et al.  Effects of clodronate and alendronate on osteoclast and osteoblast co-cultures on silk-hydroxyapatite films. , 2014, Acta biomaterialia.

[3]  S. Dixon,et al.  One- and three-dimensional growth of hydroxyapatite nanowires during sol-gel-hydrothermal synthesis. , 2012, ACS applied materials & interfaces.

[4]  David L Kaplan,et al.  Ingrowth of human mesenchymal stem cells into porous silk particle reinforced silk composite scaffolds: An in vitro study. , 2011, Acta biomaterialia.

[5]  E. Caterson,et al.  Tissue engineering of skin. , 2013, Journal of the American College of Surgeons.

[6]  S. Paek,et al.  Implantation of polymer scaffolds seeded with neural stem cells in a canine spinal cord injury model. , 2010, Cytotherapy.

[7]  Masaru Yoshida,et al.  High-water-content mouldable hydrogels by mixing clay and a dendritic molecular binder , 2010, Nature.

[8]  Yuan Yuan,et al.  RhBMP-2-loaded calcium silicate/calcium phosphate cement scaffold with hierarchically porous structure for enhanced bone tissue regeneration. , 2013, Biomaterials.

[9]  P. Ball Polymers made to measure , 1994, Nature.

[10]  R. Baker Membrane Technology and Applications , 1999 .

[11]  V. Orlovskii,et al.  Synthesis and Structure of Magnesium-Substituted Hydroxyapatite , 2003 .

[12]  Tadashi Kokubo,et al.  How useful is SBF in predicting in vivo bone bioactivity? , 2006, Biomaterials.

[13]  U Cheema,et al.  Regenerative medicine and tissue engineering- Cells and biomaterials , 2011 .

[14]  Zhengke Wang,et al.  Preparation and characterization of bionic bone structure chitosan/hydroxyapatite scaffold for bone tissue engineering , 2014, Journal of biomaterials science. Polymer edition.

[15]  D W Hutmacher,et al.  The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2. , 2009, Biomaterials.

[16]  Ali Khademhosseini,et al.  Synthesis and characterization of photocrosslinkable gelatin and silk fibroin interpenetrating polymer network hydrogels. , 2011, Acta biomaterialia.

[17]  D. Mooney,et al.  Alginate: properties and biomedical applications. , 2012, Progress in polymer science.

[18]  Ali Khademhosseini,et al.  Nanocomposite hydrogels for biomedical applications. , 2014, Biotechnology and bioengineering.

[19]  K. Byrappa,et al.  Preparation of magnesium-substituted hydroxyapatite powders by the mechanochemical-hydrothermal method. , 2004, Biomaterials.

[20]  M. Marazzi,et al.  Formulation and Characterization of Silk Fibroin Films as a Scaffold for Adipose-Derived Stem Cells in Skin Tissue Engineering , 2013, International journal of immunopathology and pharmacology.

[21]  K. Chennazhi,et al.  Effect of incorporation of nanoscale bioactive glass and hydroxyapatite in PCL/chitosan nanofibers for bone and periodontal tissue engineering. , 2013, Journal of biomedical nanotechnology.

[22]  Yining Wang,et al.  A novel bioactive three-dimensional β-tricalcium phosphate/chitosan scaffold for periodontal tissue engineering , 2010, Journal of materials science. Materials in medicine.

[23]  T. Anada,et al.  Comparative study on in vitro biocompatibility of synthetic octacalcium phosphate and calcium phosphate ceramics used clinically , 2012, Biomedical materials.

[24]  Dhirendra S Katti,et al.  Nanofibers and their applications in tissue engineering , 2006, International journal of nanomedicine.

[25]  C. Gallina,et al.  Development of morphology and function of neonatal mouse ventricular myocytes cultured on a hyaluronan‐based polymer scaffold , 2012, Journal of cellular biochemistry.

[26]  M. S. Kallos,et al.  Optimizing gelling parameters of gellan gum for fibrocartilage tissue engineering. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[27]  Caroline M Curtin,et al.  Innovative Collagen Nano‐Hydroxyapatite Scaffolds Offer a Highly Efficient Non‐Viral Gene Delivery Platform for Stem Cell‐Mediated Bone Formation , 2012, Advanced materials.

[28]  Ung-Jin Kim,et al.  Bone tissue engineering with premineralized silk scaffolds. , 2008, Bone.

[29]  S. Razavi,et al.  The beneficial effect of encapsulated human adipose-derived stem cells in alginate hydrogel on neural differentiation. , 2014, Journal of biomedical materials research. Part B, Applied biomaterials.

[30]  A. I. Liapis,et al.  Research and Development Needs and Opportunities in Freeze Drying , 1996 .

[31]  Yin Xiao,et al.  The osteogenic properties of CaP/silk composite scaffolds. , 2010, Biomaterials.

[32]  H. Tønnesen,et al.  Alginate in Drug Delivery Systems , 2002, Drug development and industrial pharmacy.

[33]  S. Venkatraman,et al.  Hyaluronic acid-based nanocomposite hydrogels for ocular drug delivery applications. , 2014, Journal of biomedical materials research. Part A.

[34]  A. L. Oliveira,et al.  Peripheral mineralization of a 3D biodegradable tubular construct as a way to enhance guidance stabilization in spinal cord injury regeneration , 2012, Journal of Materials Science: Materials in Medicine.

[35]  T. E. Abraham,et al.  Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan--a review. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[36]  Mohammad Ali Shokrgozar,et al.  Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering. , 2013, Materials science & engineering. C, Materials for biological applications.

[37]  André R. Studart,et al.  Processing Routes to Macroporous Ceramics: A Review , 2006 .

[38]  D. Hutmacher,et al.  A dual-layer silk fibroin scaffold for reconstructing the human corneal limbus. , 2012, Biomaterials.

[39]  Giovanni Vozzi,et al.  Silk fibroin/gelatin blend films crosslinked with enzymes for biomedical applications. , 2013, Macromolecular bioscience.

[40]  Chen Chang,et al.  Temporal MRI characterization of gelatin/hyaluronic acid/chondroitin sulfate sponge for cartilage tissue engineering. , 2013, Journal of biomedical materials research. Part A.

[41]  Byong-Taek Lee,et al.  Fabrication of oxidized alginate-gelatin-BCP hydrogels and evaluation of the microstructure, material properties and biocompatibility for bone tissue regeneration , 2012, Journal of biomaterials applications.

[42]  Margam Chandrasekaran,et al.  Rapid prototyping in tissue engineering: challenges and potential. , 2004, Trends in biotechnology.

[43]  J. Ferreira,et al.  Effects of Mn-doping on the structure and biological properties of β-tricalcium phosphate. , 2014, Journal of inorganic biochemistry.

[44]  David L. Kaplan,et al.  Calcium phosphate combination biomaterials as human mesenchymal stem cell delivery vehicles for bone repair. , 2011, Journal of Biomedical Materials Research. Part B - Applied biomaterials.

[45]  Robert Langer,et al.  Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment. , 2006, Journal of biomedical materials research. Part A.

[46]  P. Netti,et al.  Effect of micro- and macroporosity of bone tissue three-dimensional-poly(epsilon-caprolactone) scaffold on human mesenchymal stem cells invasion, proliferation, and differentiation in vitro. , 2010, Tissue engineering. Part A.

[47]  R. Reis,et al.  Chondrogenic potential of two hASCs subpopulations loaded onto gellan gum hydrogel evaluated in a nude mice model. , 2013, Current stem cell research & therapy.

[48]  Vassilios I. Sikavitsas,et al.  Flow Perfusion Improves Seeding of Tissue Engineering Scaffolds with Different Architectures , 2007, Annals of Biomedical Engineering.

[49]  Dietmar W. Hutmacher,et al.  Scaffold design and fabrication technologies for engineering tissues — state of the art and future perspectives , 2001, Journal of biomaterials science. Polymer edition.

[50]  W. Park,et al.  Biomimetic nanofibrous scaffolds: preparation and characterization of chitin/silk fibroin blend nanofibers. , 2006, International journal of biological macromolecules.

[51]  X. Mo,et al.  Preparation and characterization of coaxial electrospun thermoplastic polyurethane/collagen compound nanofibers for tissue engineering applications. , 2010, Colloids and surfaces. B, Biointerfaces.

[52]  Hsin-Yi Weng,et al.  Hyaluronic acid and chondrogenesis of murine bone marrow mesenchymal stem cells in chitosan sponges. , 2011, American journal of veterinary research.

[53]  Jin-Hee Moon,et al.  Microfluidic Spinning of Flat Alginate Fibers with Grooves for Cell‐Aligning Scaffolds , 2012, Advanced materials.

[54]  R. Bȩdziński,et al.  Mechanical, biological, and microstructural properties of biodegradable models of polymeric stents made of PLLA and alginate fibers. , 2011, Acta of bioengineering and biomechanics.

[55]  N. Annabi,et al.  Engineering porous scaffolds using gas-based techniques. , 2011, Current opinion in biotechnology.

[56]  H. Dietz,et al.  The genetic basis of aortic aneurysm. , 2014, Cold Spring Harbor perspectives in medicine.

[57]  Ali Samadikuchaksaraei,et al.  Synthesis and Characterization of a Laminated Hydroxyapatite/Gelatin Nanocomposite Scaffold with Controlled Pore Structure for Bone Tissue Engineering , 2010, The International journal of artificial organs.

[58]  J. Fisher,et al.  Bone tissue engineering bioreactors: dynamic culture and the influence of shear stress. , 2011, Bone.

[59]  G. Forte,et al.  Thick soft tissue reconstruction on highly perfusive biodegradable scaffolds. , 2010, Macromolecular bioscience.

[60]  N. Itoh FGF21 as a Hepatokine, Adipokine, and Myokine in Metabolism and Diseases , 2014, Front. Endocrinol..

[61]  S. Kannan,et al.  In Situ Formation and Characterization of Flourine-Substituted Biphasic Calcium Phosphate Ceramics of Varied F-HAP/β-TCP Ratios , 2005 .

[62]  Teja Guda,et al.  Development of Composite Scaffolds for Load-Bearing Segmental Bone Defects , 2013, BioMed research international.

[63]  J. M. Nóbrega,et al.  Bioinspired methodology for preparing magnetic responsive chitosan beads to be integrated in a tubular bioreactor for biomedical applications , 2013, Biomedical materials.

[64]  M. Shokrgozar,et al.  Investigation of biphasic calcium phosphate/gelatin nanocomposite scaffolds as a bone tissue engineering , 2010 .

[65]  John Wang,et al.  Mechanochemical synthesis of nanocrystalline hydroxyapatite from CaO and CaHPO4. , 2001, Biomaterials.

[66]  J. Lis,et al.  Physicochemical properties and biomimetic behaviour of α-TCP-chitosan based materials , 2014 .

[67]  F. Cui,et al.  Injectable Biocomposites for Bone Healing in Rabbit Femoral Condyle Defects , 2013, PloS one.

[68]  Jinhua Li,et al.  Self-assembled collagen-human mesenchymal stem cell microspheres for regenerative medicine. , 2007, Biomaterials.

[69]  Julian H. George,et al.  Exploring and Engineering the Cell Surface Interface , 2005, Science.

[70]  Ueon Sang Shin,et al.  Direct deposited porous scaffolds of calcium phosphate cement with alginate for drug delivery and bone tissue engineering. , 2011, Acta biomaterialia.

[71]  S. Agarwal,et al.  Use of electrospinning technique for biomedical applications , 2008 .

[72]  PeiYan Ni,et al.  Injectable and thermo-sensitive PEG-PCL-PEG copolymer/collagen/n-HA hydrogel composite for guided bone regeneration. , 2012, Biomaterials.

[73]  M. Jelínek,et al.  Antibacterial, cytotoxicity and physical properties of laser--silver doped hydroxyapatite layers. , 2013, Materials science & engineering. C, Materials for biological applications.

[74]  Li Chen,et al.  Preparation and evaluation of collagen-silk fibroin/hydroxyapatite nanocomposites for bone tissue engineering. , 2014, International journal of biological macromolecules.

[75]  R. L. Reis,et al.  Gellan gum‐based hydrogels for intervertebral disc tissue‐engineering applications , 2011, Journal of tissue engineering and regenerative medicine.

[76]  Ali Khademhosseini,et al.  Controlling the porosity and microarchitecture of hydrogels for tissue engineering. , 2010, Tissue engineering. Part B, Reviews.

[77]  Zi Yin,et al.  Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced osteogenic differentiation of mMSCs , 2012, Nanotechnology.

[78]  Junfeng Ji,et al.  The promotion of bone regeneration by nanofibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs. , 2013, Biomaterials.

[79]  A. Bandyopadhyay,et al.  ZnO, SiO2, and SrO doping in resorbable tricalcium phosphates: Influence on strength degradation, mechanical properties, and in vitro bone-cell material interactions. , 2012, Journal of biomedical materials research. Part B, Applied biomaterials.

[80]  Jöns Hilborn,et al.  Self-healing hybrid nanocomposites consisting of bisphosphonated hyaluronan and calcium phosphate nanoparticles. , 2014, Biomaterials.

[81]  S. Bhaduri,et al.  Novel microwave synthesis of amorphous calcium phosphate nanospheres. , 2012, Journal of biomedical materials research. Part B, Applied biomaterials.

[82]  D. Kaplan,et al.  Materials fabrication from Bombyx mori silk fibroin , 2011, Nature Protocols.

[83]  Changren Zhou,et al.  Osteodifferentiation of mesenchymal stem cells on chitosan/hydroxyapatite composite films. , 2014, Journal of biomedical materials research. Part A.

[84]  Wei-Wen Hu,et al.  Coelectrospinning of chitosan/alginate fibers by dual-jet system for modulating material surfaces. , 2013, Carbohydrate polymers.

[85]  M. Floren,et al.  Porous poly(D,L-lactic acid) foams with tunable structure and mechanical anisotropy prepared by supercritical carbon dioxide. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[86]  Eduardo Saiz,et al.  Sintering and robocasting of beta-tricalcium phosphate scaffolds for orthopaedic applications. , 2005, Acta biomaterialia.

[87]  Z. Bagheri,et al.  Fabrication and characterization of novel biomimetic PLLA/cellulose/hydroxyapatite nanocomposite for bone repair applications. , 2014, Materials science & engineering. C, Materials for biological applications.

[88]  Rui L Reis,et al.  Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: Scaffold design and its performance when seeded with goat bone marrow stromal cells. , 2006, Biomaterials.

[89]  J. Boateng,et al.  An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles. , 2013, Colloids and surfaces. B, Biointerfaces.

[90]  B. L. O’dell Zinc plays both structural and catalytic roles in metalloproteins. , 2009, Nutrition reviews.

[91]  H. Kim,et al.  Preparation of in situ hardening composite microcarriers: Calcium phosphate cement combined with alginate for bone regeneration , 2014, Journal of biomaterials applications.

[92]  Rui L Reis,et al.  Development of gellan gum-based microparticles/hydrogel matrices for application in the intervertebral disc regeneration. , 2011, Tissue engineering. Part C, Methods.

[93]  Jun Lee,et al.  Growth and osteogenic differentiation of alveolar human bone marrow-derived mesenchymal stem cells on chitosan/hydroxyapatite composite fabric. , 2013, Journal of biomedical materials research. Part A.

[94]  J. Ferreira,et al.  Ionic Substitutions in Biphasic Hydroxyapatite and β‐Tricalcium Phosphate Mixtures: Structural Analysis by Rietveld Refinement , 2007 .

[95]  Christian Krettek,et al.  Influence of perfusion and compression on the proliferation and differentiation of bone mesenchymal stromal cells seeded on polyurethane scaffolds. , 2012, Biomaterials.

[96]  V. Hasırcı,et al.  Collagen scaffolds with in situ‐grown calcium phosphate for osteogenic differentiation of Wharton's jelly and menstrual blood stem cells , 2012, Journal of tissue engineering and regenerative medicine.

[97]  M. Oyen,et al.  Composite electrospun gelatin fiber-alginate gel scaffolds for mechanically robust tissue engineered cornea. , 2013, Journal of the mechanical behavior of biomedical materials.

[98]  Anna Tampieri,et al.  Biomimesis and biomorphic transformations: new concepts applied to bone regeneration. , 2011, Journal of biotechnology.

[99]  T. Troczynski,et al.  Novel biomimetic hydroxyapatite/alginate nanocomposite fibrous scaffolds for bone tissue regeneration , 2013, Journal of Materials Science: Materials in Medicine.

[100]  Peter X Ma,et al.  Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. , 2009, Biomaterials.

[101]  Yong-Dae Kwon,et al.  Photo-cured hyaluronic acid-based hydrogels containing growth and differentiation factor 5 (GDF-5) for bone tissue regeneration. , 2014, Bone.

[102]  M. Prabhakaran,et al.  Electrospun aligned PHBV/collagen nanofibers as substrates for nerve tissue engineering , 2013, Biotechnology and bioengineering.

[103]  H. Rehage,et al.  Silver-doped calcium phosphate nanoparticles: synthesis, characterization, and toxic effects toward mammalian and prokaryotic cells. , 2013, Colloids and surfaces. B, Biointerfaces.

[104]  Brendon M. Baker,et al.  Fibrous hyaluronic acid hydrogels that direct MSC chondrogenesis through mechanical and adhesive cues. , 2013, Biomaterials.

[105]  M. Li,et al.  The use of silk fibroin/hydroxyapatite composite co-cultured with rabbit bone-marrow stromal cells in the healing of a segmental bone defect. , 2010, The Journal of bone and joint surgery. British volume.

[106]  A. Khademhosseini,et al.  Hydrogels in Regenerative Medicine , 2009, Advanced materials.

[107]  J. Jansen,et al.  Sodium citrate as an effective dispersant for the synthesis of inorganic-organic composites with a nanodispersed mineral phase. , 2010, Acta biomaterialia.

[108]  Rui L Reis,et al.  Use of perfusion bioreactors and large animal models for long bone tissue engineering. , 2014, Tissue engineering. Part B, Reviews.

[109]  A. Dogan,et al.  A Silver Ion-doped Calcium Phosphate-based Ceramic Nanopowder-coated Prosthesis Increased Infection Resistance , 2013, Clinical orthopaedics and related research.

[110]  Jing Zhao,et al.  Highly stable amorphous calcium phosphate porous nanospheres: microwave-assisted rapid synthesis using ATP as phosphorus source and stabilizer, and their application in anticancer drug delivery. , 2013, Chemistry.

[111]  J. Ferreira,et al.  Brushite-Forming Mg-, Zn- and Sr-Substituted Bone Cements for Clinical Applications , 2010, Materials.

[112]  R L Reis,et al.  Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic, part I (basic concepts) , 2008, Journal of tissue engineering and regenerative medicine.

[113]  J. Mano,et al.  Free-standing multilayer films made of chitosan and alginate for biomedical applications , 2012 .

[114]  Fergal J O'Brien,et al.  Cell-scaffold interactions in the bone tissue engineering triad. , 2013, European cells & materials.

[115]  Swee Hin Teoh,et al.  A biaxial rotating bioreactor for the culture of fetal mesenchymal stem cells for bone tissue engineering. , 2009, Biomaterials.

[116]  Jun Yang,et al.  Hybrid sponge comprised of galactosylated chitosan and hyaluronic acid mediates the co-culture of hepatocytes and endothelial cells. , 2014, Journal of bioscience and bioengineering.

[117]  Xuanhe Zhao,et al.  Design considerations for an integrated microphysiological muscle tissue for drug and tissue toxicity testing , 2013, Stem Cell Research & Therapy.

[118]  J. Bumgardner,et al.  Balancing mechanical strength with bioactivity in chitosan–calcium phosphate 3D microsphere scaffolds for bone tissue engineering: air- vs. freeze-drying processes , 2013, Journal of biomaterials science. Polymer edition.

[119]  R. Reis,et al.  Biocompatibility Evaluation of Ionic‐ and Photo‐Crosslinked Methacrylated Gellan Gum Hydrogels: In Vitro and In Vivo Study , 2013, Advanced healthcare materials.

[120]  Claudio Migliaresi,et al.  Silk fibroin/hyaluronic acid 3D matrices for cartilage tissue engineering. , 2013, Biomacromolecules.

[121]  M. Taya,et al.  Production of endothelial cell-enclosing alginate-based hydrogel fibers with a cell adhesive surface through simultaneous cross-linking by horseradish peroxidase-catalyzed reaction in a hydrodynamic spinning process. , 2012, Journal of bioscience and bioengineering.

[122]  R. Cameron,et al.  Chitosan/apatite composite beads prepared by in situ generation of apatite or Si-apatite nanocrystals. , 2010, Acta biomaterialia.

[123]  Wenxin Wang,et al.  Encapsulation and 3D culture of human adipose-derived stem cells in an in-situ crosslinked hybrid hydrogel composed of PEG-based hyperbranched copolymer and hyaluronic acid , 2013, Stem Cell Research & Therapy.

[124]  Hongzhen Xu,et al.  Dual Delivery of BMP-2 and bFGF from a New Nano-Composite Scaffold, Loaded with Vascular Stents for Large-Size Mandibular Defect Regeneration , 2013, International journal of molecular sciences.

[125]  Rui L. Reis,et al.  Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering. , 2009, Biomaterials.

[126]  S. Ramakrishna,et al.  Osteoblast mineralization with composite nanofibrous substrate for bone tissue regeneration , 2010, Cell biology international.

[127]  Sergio Alexandre Gehrke,et al.  Biomechanical evaluation of dental implants with three different designs: Removal torque and resonance frequency analysis in rabbits. , 2015, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[128]  Daniela F. Coutinho,et al.  Microfabricated photocrosslinkable polyelectrolyte-complex of chitosan and methacrylated gellan gum. , 2012, Journal of materials chemistry.

[129]  Q. Ping,et al.  PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy. , 2014, Biomaterials.

[130]  J. Dancis,et al.  Reproduction, fertility and developmentPapers from a Symposium on the Placenta and Fetal Membranes, 3–4 November 1990, Monash Medical Centre, Melbourne, Australia , 1992 .

[131]  Michael Jarcho,et al.  Calcium phosphate ceramics as hard tissue prosthetics. , 1981, Clinical orthopaedics and related research.

[132]  S. Catros,et al.  A nano-hydroxyapatite--pullulan/dextran polysaccharide composite macroporous material for bone tissue engineering. , 2013, Biomaterials.

[133]  David L. Kaplan,et al.  A new route for silk , 2008 .

[134]  A. Gaharwar,et al.  Highly extensible, tough, and elastomeric nanocomposite hydrogels from poly(ethylene glycol) and hydroxyapatite nanoparticles. , 2011, Biomacromolecules.

[135]  David L Kaplan,et al.  Antibiotic‐Releasing Silk Biomaterials for Infection Prevention and Treatment , 2013, Advanced functional materials.

[136]  Xingcan Shen,et al.  Silk fibroin-based scaffolds for tissue engineering , 2013, Frontiers of Materials Science.

[137]  O. Sorițău,et al.  Silicon effect on the composition and structure of nanocalcium phosphates: In vitro biocompatibility to human osteoblasts. , 2014, Materials science & engineering. C, Materials for biological applications.

[138]  Seeram Ramakrishna,et al.  Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan. , 2010, Tissue engineering. Part A.

[139]  Y. Koyama,et al.  Osteogenic activity of MG63 cells on bone-like hydroxyapatite/collagen nanocomposite sponges , 2010, Journal of materials science. Materials in medicine.

[140]  F. O'Brien,et al.  Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering , 2010, Journal of materials science. Materials in medicine.

[141]  R. Reis,et al.  Silk hydrogels from non-mulberry and mulberry silkworm cocoons processed with ionic liquids. , 2013, Acta biomaterialia.

[142]  J. Ferreira,et al.  Synthesis and thermal stability of sodium, magnesium co-substituted hydroxyapatites , 2006 .

[143]  Rui L Reis,et al.  Tissue engineering strategies applied in the regeneration of the human intervertebral disk. , 2013, Biotechnology advances.

[144]  M Busacca,et al.  A novel nano-composite multi-layered biomaterial for treatment of osteochondral lesions: technique note and an early stability pilot clinical trial. , 2010, Injury.

[145]  W. Bonfield,et al.  Hydroxyapatite reinforced polyethylene--a mechanically compatible implant material for bone replacement. , 1981, Biomaterials.

[146]  J. Fisher,et al.  In vivo bone regeneration using tubular perfusion system bioreactor cultured nanofibrous scaffolds. , 2014, Tissue engineering. Part A.

[147]  C. Finkemeier,et al.  Bone-grafting and bone-graft substitutes. , 2002, The Journal of bone and joint surgery. American volume.

[148]  K. Katti,et al.  Bone nodules on chitosan-polygalacturonic acid-hydroxyapatite nanocomposite films mimic hierarchy of natural bone. , 2011, Acta biomaterialia.

[149]  C. Migliaresi,et al.  The optimization of a scaffold for cartilage regeneration , 2013, Organogenesis.

[150]  M Bohner,et al.  Calcium orthophosphates in medicine: from ceramics to calcium phosphate cements. , 2000, Injury.

[151]  Jianliu Wang,et al.  Tissue-engineered mesh for pelvic floor reconstruction fabricated from silk fibroin scaffold with adipose-derived mesenchymal stem cells , 2013, Cell and Tissue Research.

[152]  T. Park,et al.  A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive. , 2000, Journal of biomedical materials research.

[153]  A. Sionkowska,et al.  Characterization of collagen/hydroxyapatite composite sponges as a potential bone substitute. , 2010, International journal of biological macromolecules.

[154]  William R. Wagner,et al.  Hybrid nanofibrous scaffolds from electrospinning of a synthetic biodegradable elastomer and urinary bladder matrix , 2008, Journal of biomaterials science. Polymer edition.

[155]  J. Schneider,et al.  Self-assembling peptides and proteins for nanotechnological applications. , 2004, Current opinion in structural biology.

[156]  Bo Mi Moon,et al.  A novel approach to fabricate silk nanofibers containing hydroxyapatite nanoparticles using a three-way stopcock connector , 2013, Nanoscale Research Letters.

[157]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[158]  Qing Peng,et al.  A general strategy for nanocrystal synthesis , 2005, Nature.

[159]  J.C. Elliott,et al.  Rietveld refinement of the crystallographic structure of human dental enamel apatites , 1999 .

[160]  M. Yashima,et al.  Crystal structure analysis of β-tricalcium phosphate Ca3(PO4)2 by neutron powder diffraction , 2003 .

[161]  J. Ferreira,et al.  Synthesis and Structure Refinement of Zinc-Doped β-Tricalcium Phosphate Powders , 2009 .

[162]  P. Schlesinger,et al.  Characterization of the Osteoclast Ruffled Border Chloride Channel and Its Role in Bone Resorption* , 1997, The Journal of Biological Chemistry.

[163]  Zhixiang Tong,et al.  Hyaluronic acid-based hydrogels containing covalently integrated drug depots: implication for controlling inflammation in mechanically stressed tissues. , 2013, Biomacromolecules.

[164]  Na Ren,et al.  Graphene oxide-reinforced biodegradable genipin-cross-linked chitosan fluorescent biocomposite film and its cytocompatibility , 2013, International journal of nanomedicine.

[165]  Robert Langer,et al.  Advances in tissue engineering. , 2004, Current topics in developmental biology.

[166]  R. Reis,et al.  Bioactive macro/micro porous silk fibroin/nano-sized calcium phosphate scaffolds with potential for bone-tissue-engineering applications. , 2013, Nanomedicine.

[167]  G. Vunjak‐Novakovic,et al.  Nucleation and growth of mineralized bone matrix on silk-hydroxyapatite composite scaffolds. , 2011, Biomaterials.

[168]  David L Kaplan,et al.  Silk–hyaluronan-based composite hydrogels: A novel, securable vehicle for drug delivery , 2013, Journal of biomaterials applications.

[169]  C. Cristallini,et al.  Hydroxyapatite/gelatin/gellan sponges as nanocomposite scaffolds for bone reconstruction , 2011, Journal of Materials Science: Materials in Medicine.

[170]  Deng-long Chen,et al.  Cytocompatibility of electrospun nanofiber tubular scaffolds for small diameter tissue engineering blood vessels. , 2011, International journal of biological macromolecules.

[171]  Rui L Reis,et al.  Macro/microporous silk fibroin scaffolds with potential for articular cartilage and meniscus tissue engineering applications. , 2012, Acta biomaterialia.

[172]  A. Lode,et al.  Fabrication and characterization of regenerated silk scaffolds reinforced with natural silk fibers for bone tissue engineering. , 2013, Journal of biomedical materials research. Part A.

[173]  Bruce P. Lee,et al.  Biomimetic adhesive containing nanocomposite hydrogel with enhanced materials properties , 2013 .

[174]  G. Goss,et al.  Trials to Overcome Drug Resistance to EGFR and ALK Targeted Therapies – Past, Present, and Future , 2014, Front. Oncol..

[175]  R. Eikelboom,et al.  Utilising silk fibroin membranes as scaffolds for the growth of tympanic membrane keratinocytes, and application to myringoplasty surgery , 2012, The Journal of Laryngology & Otology.

[176]  S. Dorozhkin Calcium Orthophosphates in Nature, Biology and Medicine , 2009, Materials.

[177]  C. Laurencin,et al.  Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors. , 2009, Journal of biomedical materials research. Part A.

[178]  W. R. Moore,et al.  Synthetic bone graft substitutes , 2001, ANZ journal of surgery.

[179]  K. Zierold,et al.  Potassium is Involved in Apatite Biomineralization , 1998, Journal of dental research.

[180]  R. Reis,et al.  Rheological and mechanical properties of acellular and cell-laden methacrylated gellan gum hydrogels. , 2013, Journal of biomedical materials research. Part A.

[181]  H. Chen,et al.  Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen , 2003 .

[182]  K. Min,et al.  Physical properties and biological/odontogenic effects of an experimentally developed fast-setting α-tricalcium phosphate-based pulp capping material , 2014, BMC oral health.

[183]  K. Cashman,et al.  The effect of dietary sodium intake on biochemical markers of bone metabolism in young women , 1998, British Journal of Nutrition.

[184]  J. M. Ferreira,et al.  Synthesis and Thermal Stability of Hydroxyapatite−β-Tricalcium Phosphate Composites with Cosubstituted Sodium, Magnesium, and Fluorine , 2006 .

[185]  P. Thorn,et al.  Effects of cell density and biomacromolecule addition on the flow behavior of concentrated mesenchymal cell suspensions. , 2013, Biomacromolecules.

[186]  Jayachandran Venkatesan,et al.  Chitosan Composites for Bone Tissue Engineering—An Overview , 2010, Marine drugs.

[187]  Jason A. Burdick,et al.  Hyaluronic Acid Hydrogels for Biomedical Applications , 2011, Advanced materials.

[188]  A. Salgado,et al.  De novo bone formation on macro/microporous silk and silk/nano-sized calcium phosphate scaffolds , 2013 .

[189]  K. Moriyama,et al.  Hydroxyapatite/collagen nanocomposite-coated titanium rod for achieving rapid osseointegration onto bone surface. , 2013, Journal of biomedical materials research. Part B, Applied biomaterials.

[190]  R. Reis,et al.  Macroporous hydroxyapatite scaffolds for bone tissue engineering applications: physicochemical characterization and assessment of rat bone marrow stromal cell viability. , 2009, Journal of biomedical materials research. Part A.

[191]  Allan S Hoffman,et al.  Hydrogels for biomedical applications. , 2002, Advanced drug delivery reviews.

[192]  T. Basu,et al.  Calcium phosphate nanoparticles: a study of their synthesis, characterization and mode of interaction with salmon testis DNA. , 2014, Dalton transactions.

[193]  J. Aizenberg,et al.  Skeleton of Euplectella sp.: Structural Hierarchy from the Nanoscale to the Macroscale , 2005, Science.

[194]  Lu Weiwei,et al.  RETRACTED: A novel technique to synthesize hydroxyapatite whiskers , 2008 .

[195]  Jan Feijen,et al.  Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. , 2003, Biomaterials.

[196]  J. Osborne,et al.  Collagen–PCL Sheath–Core Bicomponent Electrospun Scaffolds Increase Osteogenic Differentiation and Calcium Accretion of Human Adipose-Derived Stem Cells , 2011, Journal of biomaterials science. Polymer edition.

[197]  T. Arinzeh,et al.  Electrospun Nanofibrous Materials for Neural Tissue Engineering , 2011 .

[198]  M. Shokrgozar,et al.  Bio-hybrid silk fibroin/calcium phosphate/PLGA nanocomposite scaffold to control the delivery of vascular endothelial growth factor. , 2014, Materials science & engineering. C, Materials for biological applications.

[199]  S. Grant,et al.  Electrospinning collagen and hyaluronic acid nanofiber meshes , 2012, Journal of Materials Science: Materials in Medicine.

[200]  R. Reis,et al.  Silk Fibroin/Nano-CaP Bilayered Scaffolds for Osteochondral Tissue Engineering , 2013 .

[201]  Rekha S. Singhal,et al.  Gellan Gum: Fermentative Production, Downstream Processing and Applications , 2007 .

[202]  David L Kaplan,et al.  Bioengineered silk proteins to control cell and tissue functions. , 2013, Methods in molecular biology.

[203]  Yu-Chen Hu,et al.  Recent progresses in gene delivery-based bone tissue engineering. , 2013, Biotechnology advances.

[204]  M. H. Fernandes,et al.  Preparation and characterization of collagen-nanohydroxyapatite biocomposite scaffolds by cryogelation method for bone tissue engineering applications. , 2013, Journal of biomedical materials research. Part A.

[205]  Alan Wells,et al.  Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC , 2010, Journal of biomedicine & biotechnology.

[206]  J. Freeland-Graves,et al.  Manganese balance and clinical observations in young men fed a manganese-deficient diet. , 1987, The Journal of nutrition.

[207]  Per-Erik Jansson,et al.  Structural studies of gellan gum, an extracellular polysaccharide elaborated by Pseudomonas elodea , 1983 .

[208]  Jong Kyu Hong,et al.  Next generation of electrosprayed fibers for tissue regeneration. , 2011, Tissue engineering. Part B, Reviews.

[209]  G. Robb,et al.  Repair and Reconstruction of a Resected Tumor Defect Using a Composite of Tissue Flap–Nanotherapeutic–Silk Fibroin and Chitosan Scaffold , 2011, Annals of Biomedical Engineering.

[210]  H. Vandenburgh,et al.  Growth, differentiation, transplantation and survival of human skeletal myofibers on biodegradable scaffolds. , 2008, Biomaterials.

[211]  Leo Q Wan,et al.  A hydrogel-mineral composite scaffold for osteochondral interface tissue engineering. , 2012, Tissue engineering. Part A.

[212]  K. Ohgo,et al.  Comparative study of silk fibroin porous scaffolds derived from salt/water and sucrose/hexafluoroisopropanol in cartilage formation. , 2009, Journal of bioscience and bioengineering.

[213]  F. Sbrana,et al.  Oriented collagen nanocoatings for tissue engineering. , 2014, Colloids and surfaces. B, Biointerfaces.

[214]  Julien Andrieu,et al.  A Direct Characterization Method of the Ice Morphology. Relationship Between Mean Crystals Size and Primary Drying Times of Freeze-Drying Processes , 2004 .

[215]  P. Fabbri,et al.  Porous scaffolds of polycaprolactone reinforced with in situ generated hydroxyapatite for bone tissue engineering , 2010, Journal of materials science. Materials in medicine.

[216]  Shangtian Yang,et al.  Three-dimensional fibrous scaffolds with microstructures and nanotextures for tissue engineering , 2012 .

[217]  Andrew G Alleyne,et al.  Micro-robotic deposition guidelines by a design of experiments approach to maximize fabrication reliability for the bone scaffold application. , 2008, Acta biomaterialia.

[218]  Patrick Soon-Shiong,et al.  Induction of Cytokine Production from Human Monocytes Stimulated with Alginate , 1991, Journal of immunotherapy : official journal of the Society for Biological Therapy.

[219]  Xin Chen,et al.  Conformation transition kinetics of Bombyx mori silk protein , 2007, Proteins.

[220]  Yingjun Wang,et al.  Preparation and characterization of a novel tobramycin-containing antibacterial collagen film for corneal tissue engineering. , 2014, Acta biomaterialia.

[221]  T. Ma,et al.  In vitro evaluation of hydroxyapatite-chitosan-gelatin composite membrane in guided tissue regeneration. , 2013, Journal of biomedical materials research. Part A.

[222]  C. Rey,et al.  Mechanisms of Action and Therapeutic Potential of Strontium in Bone , 2001, Calcified Tissue International.

[223]  R L Reis,et al.  Micro-computed tomography (μ -CT) as a potential tool to assess the effect of dynamic coating routes on the formation of biomimetic apatite layers on 3D-plotted biodegradable polymeric scaffolds , 2007, Journal of materials science. Materials in medicine.

[224]  Ying-Jie Zhu,et al.  Amorphous calcium phosphate/poly(D,L-lactic acid) composite nanofibers: electrospinning preparation and biomineralization. , 2011, Journal of colloid and interface science.

[225]  Christian Jungreuthmayer,et al.  Development of a biomimetic collagen-hydroxyapatite scaffold for bone tissue engineering using a SBF immersion technique. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[226]  Jie Zhao,et al.  Amorphous calcium phosphate and its application in dentistry , 2011, Chemistry Central journal.

[227]  B. Ding,et al.  Biomimetic electrospun nanofibrous structures for tissue engineering. , 2013, Materials today.

[228]  J. A. Cooper,et al.  Hybrid hyaluronic acid hydrogel/poly(ɛ-caprolactone) scaffold provides mechanically favorable platform for cartilage tissue engineering studies. , 2014, Journal of biomedical materials research. Part A.

[229]  W. Ryu,et al.  Mechanically-reinforced electrospun composite silk fibroin nanofibers containing hydroxyapatite nanoparticles. , 2014, Materials science & engineering. C, Materials for biological applications.

[230]  G. Song,et al.  Fabrication of nano-fibrous poly(L-lactic acid) scaffold reinforced by surface modified chitosan micro-fiber. , 2013, International journal of biological macromolecules.

[231]  A. Youzbashi,et al.  Sol-Gel Synthesis of FHA Nanoparticles and CDHA Agglomerates from a Mixture with a Nonstochiometric Ca/P Ratio , 2008 .

[232]  Joseph Stokes,et al.  Electrospun composites of PHBV, silk fibroin and nano-hydroxyapatite for bone tissue engineering. , 2013, Materials science & engineering. C, Materials for biological applications.

[233]  C. Schauer,et al.  Electrospun hydroxyapatite-containing chitosan nanofibers crosslinked with genipin for bone tissue engineering. , 2012, Biomaterials.

[234]  Masanori Kikuchi,et al.  Hydroxyapatite/collagen bone-like nanocomposite. , 2013, Biological & pharmaceutical bulletin.

[235]  J. Fraser,et al.  Hyaluronan: its nature, distribution, functions and turnover , 1997, Journal of internal medicine.

[236]  John B. Matson,et al.  Peptide Self-Assembly for Crafting Functional Biological Materials. , 2011, Current opinion in solid state & materials science.

[237]  Anja Lode,et al.  Direct Plotting of Three‐Dimensional Hollow Fiber Scaffolds Based on Concentrated Alginate Pastes for Tissue Engineering , 2013, Advanced healthcare materials.

[238]  R L Reis,et al.  Nucleation and growth of biomimetic apatite layers on 3D plotted biodegradable polymeric scaffolds: effect of static and dynamic coating conditions. , 2009, Acta biomaterialia.

[239]  J. Ai,et al.  In vitro evaluation of biomimetic nanocomposite scaffold using endometrial stem cell derived osteoblast-like cells. , 2013, Tissue & cell.

[240]  M. Vallet‐Regí,et al.  Structural study and stability of hydroxyapatite and beta-tricalcium phosphate: two important bioceramics. , 2000, Journal of biomedical materials research.

[241]  Wen‐Cheng Chen,et al.  Characterization of controlled highly porous hyaluronan/gelatin cross-linking sponges for tissue engineering. , 2012, Journal of the mechanical behavior of biomedical materials.

[242]  J. G. Martínez,et al.  Fabrication of conductive electrospun silk fibroin scaffolds by coating with polypyrrole for biomedical applications. , 2012, Bioelectrochemistry.

[243]  Song Li,et al.  The use of hyaluronan to regulate protein adsorption and cell infiltration in nanofibrous scaffolds. , 2012, Biomaterials.

[244]  R. Reis,et al.  Novel hydroxyapatite/carboxymethylchitosan composite scaffolds prepared through an innovative "autocatalytic" electroless coprecipitation route. , 2009, Journal of biomedical materials research. Part A.

[245]  S. Ichinose,et al.  The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagen composite biomaterial, and its function as a carrier of rhBMP-2. , 2001, Journal of Biomedical Materials Research.

[246]  J. Gómez-Morales,et al.  Nanosized Hydroxyapatite Precipitation from Homogeneous Calcium/Citrate/Phosphate Solutions Using Microwave and Conventional Heating , 1998 .

[247]  K. Murase,et al.  Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route , 2013, International journal of molecular sciences.

[248]  Tzu-Wei Wang,et al.  Regulation of adult human mesenchymal stem cells into osteogenic and chondrogenic lineages by different bioreactor systems. , 2009, Journal of biomedical materials research. Part A.

[249]  A. Yamazaki,et al.  Control of gene transfer on a DNA-fibronectin-apatite composite layer by the incorporation of carbonate and fluoride ions. , 2011, Biomaterials.

[250]  K. Br,et al.  Current status of DNA vaccines in veterinary medicine. , 2000 .

[251]  Silvia Farè,et al.  Preparation and Characterization of Shape Memory Polymer Scaffolds via Solvent Casting/Particulate Leaching , 2012, Journal of applied biomaterials & functional materials.

[252]  S. Mittler,et al.  Orientation distribution of highly oriented type I collagen deposited on flat samples with different geometries. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[253]  R. Cameron,et al.  Osteoinduction by combining bone morphogenetic protein (BMP)-2 with a bioactive novel nanocomposite , 2012, Bone & joint research.

[254]  K. Marra,et al.  Synthesis and characterization of collagen/hyaluronan/chitosan composite sponges for potential biomedical applications. , 2009, Acta biomaterialia.

[255]  Liang Zhao,et al.  An injectable calcium phosphate-alginate hydrogel-umbilical cord mesenchymal stem cell paste for bone tissue engineering. , 2010, Biomaterials.

[256]  W. Świȩszkowski,et al.  Electrospun bio-composite P(LLA-CL)/collagen I/collagen III scaffolds for nerve tissue engineering. , 2012, Journal of biomedical materials research. Part B, Applied biomaterials.

[257]  A. Secord,et al.  The search for biomarkers to direct antiangiogenic treatment in epithelial ovarian cancer. , 2014, Gynecologic oncology.

[258]  L. Mongeau,et al.  Characterization of a hierarchical network of hyaluronic acid/gelatin composite for use as a smart injectable biomaterial. , 2012, Macromolecular bioscience.

[259]  N. Drozdova,et al.  Nanocrystalline hydroxyapatite ceramics produced by low-temperature sintering after high-pressure treatment , 2008 .

[260]  David L Kaplan,et al.  Silk as a Biomaterial. , 2007, Progress in polymer science.

[261]  Seeram Ramakrishna,et al.  Artificial neural network for modeling the elastic modulus of electrospun polycaprolactone/gelatin scaffolds. , 2014, Acta biomaterialia.

[262]  R. Reis,et al.  Gellan Gum-Based Hydrogel Bilayered Scaffolds for Osteochondral Tissue Engineering , 2013 .

[263]  Makarand V Risbud,et al.  Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. , 2005, Biomaterials.

[264]  D. Hutmacher,et al.  Development of a pre-vascularized 3D scaffold-hydrogel composite graft using an arterio-venous loop for tissue engineering applications , 2012, Journal of biomaterials applications.

[265]  Jan Feijen,et al.  Phase-Separation Processes in Polymer-Solutions in Relation to Membrane Formation , 1996 .

[266]  Rumiko Matsuoka,et al.  Micro and nano-scale in vitro 3D culture system for cardiac stem cells. , 2010, Journal of biomedical materials research. Part A.

[267]  J. Jansen,et al.  The ability of a collagen/calcium phosphate scaffold to act as its own vector for gene delivery and to promote bone formation via transfection with VEGF(165). , 2010, Biomaterials.

[268]  J. Hilborn,et al.  Minimally invasive mandibular bone augmentation using injectable hydrogels , 2012, Journal of tissue engineering and regenerative medicine.

[269]  K. S. Ng,et al.  In vitro ligament-bone interface regeneration using a trilineage coculture system on a hybrid silk scaffold. , 2012, Biomacromolecules.

[270]  K. Kusumoto,et al.  Bone regeneration with BMP-2 and hydroxyapatite in critical-size calvarial defects in rats. , 2012, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[271]  Yanzhi Xia,et al.  Antifungal Activity and Cytotoxicity of Zinc, Calcium, or Copper Alginate Fibers , 2012, Biological Trace Element Research.

[272]  Kazutoshi Haraguchi,et al.  Nanocomposite gels : new advanced functional soft materials , 2007 .

[273]  Esmaiel Jabbari,et al.  Quantitative analysis of interconnectivity of porous biodegradable scaffolds with micro-computed tomography. , 2004, Journal of biomedical materials research. Part A.

[274]  Hong Liu,et al.  Bone repair by periodontal ligament stem cellseeded nanohydroxyapatite-chitosan scaffold , 2012, International journal of nanomedicine.

[275]  V. Locatelli,et al.  Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis , 2014, International journal of endocrinology.

[276]  J. Bonevich,et al.  Preparation and Properties of Nanoparticles of Calcium Phosphates With Various Ca/P Ratios , 2010, Journal of research of the National Institute of Standards and Technology.

[277]  Cheng Yan,et al.  Polyurethane (PU) scaffolds prepared by solvent casting/particulate leaching (SCPL) combined with centrifugation , 2010 .

[278]  J. Islam,et al.  Fabrication and characterization of gelatin-based biocompatible porous composite scaffold for bone tissue engineering. , 2012, Journal of biomedical materials research. Part A.

[279]  Shingo Niimi,et al.  Spheroid formation and expression of liver-specific functions of human hepatocellular carcinoma-derived FLC-4 cells cultured in lactose-silk fibroin conjugate sponges. , 2011, Biomacromolecules.

[280]  A. Salgado,et al.  Angiogenic potential of gellan-gum-based hydrogels for application in nucleus pulposus regeneration: in vivo study. , 2012, Tissue engineering. Part A.

[281]  M. Marcacci,et al.  Arthroscopic collagen meniscus implant results at 6 to 8 years follow up , 2007, Knee Surgery, Sports Traumatology, Arthroscopy.

[282]  J. Rocha,et al.  Synthesis and characterization of magnesium substituted biphasic mixtures of controlled hydroxyapatite/β-tricalcium phosphate ratios , 2005 .

[283]  R. Marchant,et al.  Design properties of hydrogel tissue-engineering scaffolds , 2011, Expert review of medical devices.

[284]  C. Colombeix,et al.  The association of hydrogel and biphasic calcium phosphate in the treatment of dehiscence-type peri-implant defects: an experimental study in dogs , 2013, Journal of Materials Science: Materials in Medicine.

[285]  R. Reis,et al.  Optimized electro‐ and wet‐spinning techniques for the production of polymeric fibrous scaffolds loaded with bisphosphonate and hydroxyapatite , 2011, Journal of tissue engineering and regenerative medicine.

[286]  Shengmin Zhang,et al.  Collagen/silk fibroin bi-template induced biomimetic bone-like substitutes. , 2011, Journal of biomedical materials research. Part A.

[287]  D. Petri,et al.  Synthesis and characterization of xanthan-hydroxyapatite nanocomposites for cellular uptake. , 2014, Materials science & engineering. C, Materials for biological applications.

[288]  M. Gümüşderelioğlu,et al.  Microwave‐assisted fabrication of chitosan–hydroxyapatite superporous hydrogel composites as bone scaffolds , 2015, Journal of tissue engineering and regenerative medicine.

[289]  J. Ferreira,et al.  Formation of Strontium‐Stabilized β‐Tricalcium Phosphate from Calcium‐Deficient Apatite , 2006 .

[290]  C. Laurencin,et al.  Development of novel tissue engineering scaffolds via electrospinning , 2004, Expert opinion on biological therapy.

[291]  C. Kirkpatrick,et al.  In vitro evaluation of biomimetic chitosan–calcium phosphate scaffolds with potential application in bone tissue engineering , 2013, Biomedical materials.

[292]  J. Mano,et al.  Materials of marine origin: a review on polymers and ceramics of biomedical interest , 2012 .

[293]  A. Esmaeili,et al.  Platelet-rich plasma application in chondrogenesis , 2014, Advanced biomedical research.

[294]  J. Hilborn,et al.  Injectable cell-free template for bone-tissue formation. , 2009, Journal of biomedical materials research. Part A.

[295]  K. Kandori,et al.  Preparation and characterization of carbonated barium-calcium hydroxyapatite solid solutions. , 2005, Journal of colloid and interface science.