A cellular perspective to bioceramic scaffolds for bone tissue engineering: the state of the art.

A vast number of manufacturing techniques have been employed in the last five years to manufacture three dimensional (3D) calcium phosphate (CaP) scaffolds, with the intention to replicate the architecture of native bone as well as to repair and restore bone function. Design features such as architectural control and sintering temperature and their impact on scaffold performance is presented in this review. In vitro cell responses to bioceramic scaffolds and their in vivo performances have been enhanced. Current frontiers of active research on HA scaffolds have included the relationship between fluid flow and mechanotransduction as well as cell signaling pathways that induce endothelial cell recruitment and angiogenesis. Additionally, current research has focused on a better understanding of cell signaling and its environmental cues. The availability of non-invasive and non-destructive quantitative imaging modalities has also become critical in aiding the characterization of scaffolds and predicting scaffold performance. It is thus anticipated that further knowledge gained from this research will allow the overall advancement of scaffolds that can be clinically used to restore large bone defects.

[1]  Eduardo Saiz,et al.  Preparation of porous hydroxyapatite scaffolds , 2007 .

[2]  T. Ikoma,et al.  Control of pore structure and mechanical property in hydroxyapatite/collagen composite using unidirectional ice growth , 2006 .

[3]  C James Kirkpatrick,et al.  Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials. , 2007, Biomaterials.

[4]  S Prohaska,et al.  Stereological measures of trabecular bone structure: comparison of 3D micro computed tomography with 2D histological sections in human proximal tibial bone biopsies , 2005, Journal of microscopy.

[5]  J. Frangos,et al.  Alkaline phosphatase in osteoblasts is down-regulated by pulsatile fluid flow , 2009, Calcified Tissue International.

[6]  G. Daculsi,et al.  A comparative study of biphasic calcium phosphate ceramics for human mesenchymal stem-cell-induced bone formation. , 2005, Biomaterials.

[7]  Cato T Laurencin,et al.  Bioreactor-based bone tissue engineering: the influence of dynamic flow on osteoblast phenotypic expression and matrix mineralization. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Qiong Wu,et al.  Evaluation of three-dimensional scaffolds made of blends of hydroxyapatite and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) for bone reconstruction. , 2004, Biomaterials.

[9]  J. Ong,et al.  Effects of trabecular calcium phosphate scaffolds on stress signaling in osteoblast precursor cells. , 2007, Biomaterials.

[10]  Yan Li,et al.  In vitro aging of mineralized collagen-based composite as guided tissue regeneration membrane , 2006 .

[11]  Fuzhai Cui,et al.  In vitro degradation of porous nano-hydroxyapatite/collagen/PLLA scaffold reinforced by chitin fibres , 2006 .

[12]  N. Mostafa.  Characterization, thermal stability and sintering of hydroxyapatite powders prepared by different routes , 2005 .

[13]  P. Zysset,et al.  Hydroxyapatite cement scaffolds with controlled macroporosity: fabrication protocol and mechanical properties. , 2003, Biomaterials.

[14]  Jiang Chang,et al.  pH-compensation effect of bioactive inorganic fillers on the degradation of PLGA , 2005 .

[15]  R Borojevic,et al.  Characterization of a bovine collagen-hydroxyapatite composite scaffold for bone tissue engineering. , 2003, Biomaterials.

[16]  Carl G Simon,et al.  Self‐hardening calcium phosphate composite scaffold for bone tissue engineering , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[17]  Millie Hughes-Fulford,et al.  Signal Transduction and Mechanical Stress , 2004, Science's STKE.

[18]  Eduardo Saiz,et al.  Freeze casting of hydroxyapatite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[19]  G. Daculsi,et al.  Macroporous biphasic calcium phosphate ceramics: influence of macropore diameter and macroporosity percentage on bone ingrowth. , 1998, Biomaterials.

[20]  Moustapha Kassem,et al.  Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds. , 2007, Biomaterials.

[21]  M. Baumann,et al.  Hydroxyapatite accelerates differentiation and suppresses growth of MC3T3-E1 osteoblasts. , 2003, Journal of biomedical materials research. Part A.

[22]  K. Nishizawa,et al.  Initial anchoring and proliferation of fibroblast L-929 cells on unstable surface of calcium phosphate ceramics. , 1999, Journal of bioscience and bioengineering.

[23]  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.

[24]  J. Ong,et al.  Characterization of biomimetic calcium phosphate on phosphorylated chitosan films. , 2007, Journal of biomedical materials research. Part A.

[25]  S. Cowin.  Bone mechanics handbook , 2001 .

[26]  J. Jansen,et al.  Ceramic composites as matrices and scaffolds for drug delivery in tissue engineering. , 2007, Advanced drug delivery reviews.

[27]  A. Mikos,et al.  Effect of convection on osteoblastic cell growth and function in biodegradable polymer foam scaffolds. , 2001, Biomaterials.

[28]  J. Chevalier,et al.  Effect of micro- and macroporosity of bone substitutes on their mechanical properties and cellular response , 2003, Journal of materials science. Materials in medicine.

[29]  Hockin H. K. Xu,et al.  Injectable and macroporous calcium phosphate cement scaffold. , 2006, Biomaterials.

[30]  M. Gelinsky,et al.  Ectopic bone formation in nude rats using human osteoblasts seeded poly(3)hydroxybutyrate embroidery and hydroxyapatite-collagen tapes constructs. , 2006, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[31]  J. Davies,et al.  Resorption of sintered synthetic hydroxyapatite by osteoclasts in vitro. , 1993, Biomaterials.

[32]  P. Ma,et al.  Polymer/Ceramic Composite Scaffolds for Bone Tissue Engineering , 2005 .

[33]  J A Frangos,et al.  Steady and Transient Fluid Shear Stress Stimulate NO Release in Osteoblasts Through Distinct Biochemical Pathways , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  T. Webster,et al.  Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics. , 2000, Journal of biomedical materials research.

[35]  Fuzhai Cui,et al.  Chemical characteristics and cytocompatibility of collagen-based scaffold reinforced by chitin fibers for bone tissue engineering. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[36]  S. Cowin.  Strength of Trabecular Bone , 2001 .

[37]  Robert E Guldberg,et al.  Effects of medium perfusion rate on cell-seeded three-dimensional bone constructs in vitro. , 2003, Tissue engineering.

[38]  Paul Roschger,et al.  Biomimetic mineral-organic composite scaffolds with controlled internal architecture , 2005, Journal of materials science. Materials in medicine.

[39]  S. Asko-Seljavaara,et al.  Compressive strength of calcium carbonate and hydroxyapatite implants after bone-marrow-induced osteogenesis. , 1998, Biomaterials.

[40]  F. Müller,et al.  Calcium phosphate nucleation on cellulose fabrics , 2006 .

[41]  J A Planell,et al.  Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an alpha-TCP paste. , 2004, Biomaterials.

[42]  T. Yamashita,et al.  Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy. , 2004, Biomaterials.

[43]  Ralph Müller,et al.  Nondestructive micro-computed tomography for biological imaging and quantification of scaffold-bone interaction in vivo. , 2007, Biomaterials.

[44]  C. Laurencin,et al.  An in-vitro evaluation of coralline porous hydroxyapatite as a scaffold for osteoblast growth. , 1994, Clinical materials.

[45]  Jos Vander Sloten,et al.  Micro-CT-based screening of biomechanical and structural properties of bone tissue engineering scaffolds , 2006, Medical and Biological Engineering and Computing.

[46]  Junzo Tanaka,et al.  Transplantation of cultured bone cells using combinations of scaffolds and culture techniques. , 2003, Biomaterials.

[47]  N. Araki,et al.  Slow release of anticancer drugs from porous calcium hydroxyapatite ceramic , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[48]  H. Kim,et al.  Initial responses of human osteoblasts to sol-gel modified titanium with hydroxyapatite and titania composition. , 2006, Acta biomaterialia.

[49]  Dietmar W Hutmacher,et al.  Assessment of bone ingrowth into porous biomaterials using MICRO-CT. , 2007, Biomaterials.

[50]  R. Reis,et al.  Hydroxyapatite reinforcement of different starch-based polymers affects osteoblast-like cells adhesion/spreading and proliferation , 2005 .

[51]  K. Hong,et al.  Osteoconduction at porous hydroxyapatite with various pore configurations. , 2000, Biomaterials.

[52]  Miqin Zhang,et al.  Preparation of porous hydroxyapatite scaffolds by combination of the gel-casting and polymer sponge methods. , 2003, Biomaterials.

[53]  S. Ramakrishna,et al.  Nanoporous hydroxy-carbonate apatite scaffold made of natural bone , 2006 .

[54]  Ikuho Yonezawa,et al.  The effect of the microstructure of beta-tricalcium phosphate on the metabolism of subsequently formed bone tissue. , 2007, Biomaterials.

[55]  F. E. Wiria,et al.  Poly-ε-caprolactone/hydroxyapatite for tissue engineering scaffold fabrication via selective laser sintering , 2007 .

[56]  C T Laurencin,et al.  Poly(lactide-co-glycolide)/hydroxyapatite delivery of BMP-2-producing cells: a regional gene therapy approach to bone regeneration. , 2001, Biomaterials.

[57]  A. Boccaccini,et al.  Bioactive coatings by vaterite deposition on polymer substrates of different composition and morphology , 2007 .

[58]  John M. Powers,et al.  Hydroxyapatite fiber reinforced poly(α-hydroxy ester) foams for bone regeneration , 1998 .

[59]  H. Ohgushi,et al.  Bonding osteogenesis in coralline hydroxyapatite combined with bone marrow cells. , 1991, Biomaterials.

[60]  Samuel I Stupp,et al.  Colonization of organoapatite-titanium mesh by preosteoblastic cells. , 2003, Journal of biomedical materials research. Part A.

[61]  C. Wen,et al.  Sol-gel derived HA/TiO2 double coatings on Ti scaffolds for orthopaedic applications , 2006 .

[62]  Emilija Fidancevska,et al.  Fabrication and characterization of porous bioceramic composites based on hydroxyapatite and titania , 2007 .

[63]  N. Araki,et al.  Calcium hydroxyapatite ceramic used as a delivery system for antibiotics. , 1992, The Journal of bone and joint surgery. British volume.

[64]  Xing‐dong Zhang,et al.  Proliferation and bone-related gene expression of osteoblasts grown on hydroxyapatite ceramics sintered at different temperature. , 2004, Biomaterials.

[65]  J. P. LeGeros,et al.  Biphasic calcium phosphate bioceramics: preparation, properties and applications , 2003, Journal of materials science. Materials in medicine.

[66]  C. Laurencin,et al.  17 Polymer/Calcium Phosphate Scaffolds for Bone Tissue Engineering , 2006 .

[67]  A. Salgado,et al.  Multichannel mould processing of 3D structures from microporous coralline hydroxyapatite granules and chitosan support materials for guided tissue regeneration/engineering , 2004, Journal of materials science. Materials in medicine.

[68]  M. Shaw,et al.  Biodegradable HA-PLA 3-D porous scaffolds: effect of nano-sized filler content on scaffold properties. , 2005, Acta biomaterialia.

[69]  Wei Dong,et al.  Collagen-based implants reinforced by chitin fibres in a goat shank bone defect model. , 2006, Biomaterials.

[70]  Scott P. Bruder,et al.  CHAPTER 48 – BONE REGENERATION THROUGH CELLULAR ENGINEERING , 2000 .

[71]  X. Miao,et al.  Porous calcium phosphate ceramics prepared by coating polyurethane foams with calcium phosphate cements , 2004 .

[72]  Melissa L. Knothe Tate,et al.  Interstitial Fluid Flow , 2001 .

[73]  D. Puleo,et al.  Osteoblasts on hydroxyapatite, alumina and bone surfaces in vitro: morphology during the first 2 h of attachment. , 1992, Biomaterials.

[74]  Y. Gong,et al.  A study on the bioactivity of chitosan/nano-hydroxyapatite composite scaffolds for bone tissue engineering , 2006 .

[75]  D. B. Burr,et al.  Shear Strength and Fatigue Properties of Human Cortical Bone Determined from Pure Shear Tests , 2001, Calcified Tissue International.

[76]  L. Brinson,et al.  A bioactive titanium foam scaffold for bone repair. , 2005, Acta biomaterialia.

[77]  A Tampieri,et al.  Porosity-graded hydroxyapatite ceramics to replace natural bone. , 2001, Biomaterials.

[78]  Ralph Müller,et al.  Architecture and properties of anisotropic polymer composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[79]  Byung-Soo Kim,et al.  Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[80]  T. Tanabe,et al.  Preparation of collagen/calcium phosphate multilayer sheet using enzymatic mineralization. , 2004, Biomaterials.

[81]  K. Peng,et al.  Electrophoretic deposition of porous hydroxyapatite scaffold. , 2003, Biomaterials.

[82]  R. Legeros,et al.  Properties of osteoconductive biomaterials: calcium phosphates. , 2002, Clinical orthopaedics and related research.

[83]  I. Ono,et al.  A study on bone induction in hydroxyapatite combined with bone morphogenetic protein. , 1992, Plastic and reconstructive surgery.

[84]  Liang Hong,et al.  Synthesis and characterization of hydroxyapatite–bacterial cellulose nanocomposites , 2006 .

[85]  Wei Cheng,et al.  Fabrication and characterization of β-dicalcium silicate/poly(d,l-lactic acid) composite scaffolds , 2005 .

[86]  Amy J Wagoner Johnson,et al.  The mechanical properties and osteoconductivity of hydroxyapatite bone scaffolds with multi-scale porosity. , 2007, Biomaterials.

[87]  P. A. Revell,et al.  Microporosity enhances bioactivity of synthetic bone graft substitutes , 2005, Journal of materials science. Materials in medicine.

[88]  R L Reis,et al.  Cytocompatibility and response of osteoblastic-like cells to starch-based polymers: effect of several additives and processing conditions. , 2001, Biomaterials.

[89]  S. Bhaduri,et al.  Osteoblast proliferation on neat and apatite-like calcium phosphate-coated titanium foam scaffolds , 2007 .

[90]  S. Cowin,et al.  Bone Mechanics Handbook, 2nd Edition. - , 2003 .

[91]  Roger Zauel,et al.  3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. , 2005, Journal of biomechanics.

[92]  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.

[93]  Hideki Yoshikawa,et al.  A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2). , 2005, Osteoarthritis and cartilage.

[94]  R. Ewers,et al.  Exogenous recombinant human BMP-2 has little initial effects on human osteoblastic cells cultured on collagen type I coated/noncoated hydroxyapatite ceramic granules. , 2007, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[95]  Hideki Yoshikawa,et al.  Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite. , 2005, Biomaterials.

[96]  P. Chu,et al.  Bioactive titanium-particle-containing dicalcium silicate coating , 2005 .

[97]  S. Teoh,et al.  In vitro degradation of novel bioactive polycaprolactone—20% tricalcium phosphate composite scaffolds for bone engineering , 2007 .

[98]  Young-Hag Koh,et al.  Fabrication of poly(ε-caprolactone)/hydroxyapatite scaffold using rapid direct deposition , 2006 .

[99]  N. Sharkey,et al.  Bone ingrowth and mechanical properties of coralline hydroxyapatite 1 yr after implantation. , 1993, Biomaterials.

[100]  C. Simon,et al.  Fast setting calcium phosphate-chitosan scaffold: mechanical properties and biocompatibility. , 2005, Biomaterials.

[101]  H. Tsutsumi,et al.  Preparation of photo-patterned polymer–hydroxyapatite composites , 2003 .

[102]  T. Keaveny,et al.  Effects of in vitro bone formation on the mechanical properties of a trabeculated hydroxyapatite bone substitute. , 2006, Journal of biomedical materials research. Part A.

[103]  L. Grover,et al.  Preparation of macroporous calcium phosphate cement tissue engineering scaffold. , 2002, Biomaterials.

[104]  Anna Tampieri,et al.  Nucleation of biomimetic apatite in synthetic body fluids: dense and porous scaffold development. , 2005, Biomaterials.

[105]  Antonios G. Mikos,et al.  Mineralized matrix deposition by marrow stromal osteoblasts in 3D perfusion culture increases with increasing fluid shear forces , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[106]  Joo L. Ong,et al.  Bioceramics for Tissue Engineering Applications-A Review , 2006 .

[107]  Huipin Yuan,et al.  3D microenvironment as essential element for osteoinduction by biomaterials. , 2005, Biomaterials.