Recent advances in bone tissue engineering scaffolds.

Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, made of biodegradable materials that harbor different growth factors, drugs, genes, or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved.

[1]  Vamsi Krishna Balla,et al.  Porous tantalum structures for bone implants: fabrication, mechanical and in vitro biological properties. , 2010, Acta biomaterialia.

[2]  J. Coleman,et al.  Structure and mechanism of alkaline phosphatase. , 1992, Annual review of biophysics and biomolecular structure.

[3]  Matthew C. Phipps,et al.  Increasing the pore sizes of bone-mimetic electrospun scaffolds comprised of polycaprolactone, collagen I and hydroxyapatite to enhance cell infiltration. , 2012, Biomaterials.

[4]  K. Woo,et al.  Insulin-like growth factor 2 promotes osteogenic cell differentiation in the parthenogenetic murine embryonic stem cells. , 2012, Tissue engineering. Part A.

[5]  David F. Williams On the mechanisms of biocompatibility. , 2008, Biomaterials.

[6]  Gadi Pelled,et al.  Targeted gene-and-host progenitor cell therapy for nonunion bone fracture repair. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[7]  Richard O. Hynes,et al.  The Extracellular Matrix: Not Just Pretty Fibrils , 2009, Science.

[8]  Wei Fan,et al.  Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering. , 2012, Biomaterials.

[9]  M. Mohammadi,et al.  The FGF family: biology, pathophysiology and therapy , 2009, Nature Reviews Drug Discovery.

[10]  Alberto Diaspro,et al.  Order versus Disorder: in vivo bone formation within osteoconductive scaffolds , 2012, Scientific Reports.

[11]  W. Thein-Han,et al.  Collagen-calcium phosphate cement scaffolds seeded with umbilical cord stem cells for bone tissue engineering. , 2011, Tissue engineering. Part A.

[12]  Elliot P. Douglas,et al.  Bone structure and formation: A new perspective , 2007 .

[13]  R. Emery,et al.  Evaluation of VEGF‐mediated signaling in primary human cells reveals a paracrine action for VEGF in osteoblast‐mediated crosstalk to endothelial cells , 2008, Journal of cellular physiology.

[14]  Günter Finkenzeller,et al.  Bone formation and neovascularization mediated by mesenchymal stem cells and endothelial cells in critical-sized calvarial defects. , 2011, Tissue engineering. Part A.

[15]  M. Menger,et al.  In vitro and in vivo evaluation of a novel nanosize hydroxyapatite particles/poly(ester-urethane) composite scaffold for bone tissue engineering. , 2010, Acta biomaterialia.

[16]  Michael J Yaszemski,et al.  Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. , 2009, Biomaterials.

[17]  Richard Appleyard,et al.  The influence hydroxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coated with hydroxyapatite-PCL composites. , 2010, Biomaterials.

[18]  N. Kuboyama,et al.  A biodegradable porous composite scaffold of PGA/beta-TCP for bone tissue engineering. , 2010, Bone.

[19]  William R. Heineman,et al.  Revolutionizing biodegradable metals , 2009 .

[20]  J. Bouler,et al.  Calcium phosphate biomaterials as bone drug delivery systems: a review. , 2010, Drug discovery today.

[21]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[22]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

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

[24]  B Vamsi Krishna,et al.  Processing and biocompatibility evaluation of laser processed porous titanium. , 2007, Acta biomaterialia.

[25]  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.

[26]  M. Shie,et al.  The role of silicon in osteoblast-like cell proliferation and apoptosis. , 2011, Acta biomaterialia.

[27]  D. Stewart,et al.  Effect of cell‐based VEGF gene therapy on healing of a segmental bone defect , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  Antonios G Mikos,et al.  Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. , 2008, Bone.

[29]  A. J. Putnam,et al.  Mesenchymal stem cells from adipose and bone marrow promote angiogenesis via distinct cytokine and protease expression mechanisms , 2011, Angiogenesis.

[30]  S. Bose,et al.  Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: a review. , 2012, Acta biomaterialia.

[31]  Amit Bandyopadhyay,et al.  Processing of controlled porosity ceramic structures via fused deposition , 1999 .

[32]  Larry L. Hench,et al.  Bioceramics: From Concept to Clinic , 1991 .

[33]  Gang Liu,et al.  A highly homozygous and parthenogenetic human embryonic stem cell line derived from a one-pronuclear oocyte following in vitro fertilization procedure , 2007, Cell Research.

[34]  M. Casal,et al.  Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery) , 2008, Journal of tissue engineering and regenerative medicine.

[35]  Vamsi Krishna Balla,et al.  Microwave‐sintered 3D printed tricalcium phosphate scaffolds for bone tissue engineering , 2013, Journal of tissue engineering and regenerative medicine.

[36]  Heungsoo Shin,et al.  Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. , 2007, Advanced drug delivery reviews.

[37]  Wojciech Swieszkowski,et al.  Highly porous titanium scaffolds for orthopaedic applications. , 2010, Journal of biomedical materials research. Part B, Applied biomaterials.

[38]  S. Cartmell,et al.  Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded) allograft. , 2007, European cells & materials.

[39]  Amit Bandyopadhyay,et al.  Effects of silica and zinc oxide doping on mechanical and biological properties of 3D printed tricalcium phosphate tissue engineering scaffolds. , 2012, Dental materials : official publication of the Academy of Dental Materials.

[40]  C. Plank,et al.  Future of local bone regeneration - Protein versus gene therapy. , 2011, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[41]  A. Bandyopadhyay,et al.  Understanding the influence of MgO and SrO binary doping on the mechanical and biological properties of beta-TCP ceramics. , 2010, Acta biomaterialia.

[42]  Cato T Laurencin,et al.  Tissue engineering of bone: material and matrix considerations. , 2008, The Journal of bone and joint surgery. American volume.

[43]  D. Prockop,et al.  Concise Review: Mesenchymal Stem/Multipotent Stromal Cells: The State of Transdifferentiation and Modes of Tissue Repair—Current Views , 2007, Stem cells.

[44]  Marcus Textor,et al.  Enhanced osteoblastic activity and bone regeneration using surface-modified porous bioactive glass scaffolds. , 2010, Journal of biomedical materials research. Part A.

[45]  Antonios G. Mikos,et al.  In Vitro and In Vivo Release of Vascular Endothelial Growth Factor from Gelatin Microparticles and Biodegradable Composite Scaffolds , 2008, Pharmaceutical Research.

[46]  Vamsi Krishna Balla,et al.  Surface modification of laser-processed porous titanium for load-bearing implants , 2008 .

[47]  H. Fischer,et al.  Scaffolds for bone healing: concepts, materials and evidence. , 2011, Injury.

[48]  A. Bandyopadhyay,et al.  From CT Scan to Ceramic Bone Graft , 2003 .

[49]  Jeroen Rouwkema,et al.  Vascularization in tissue engineering. , 2008, Trends in biotechnology.

[50]  M. Pollak The insulin and insulin-like growth factor receptor family in neoplasia: an update , 2012, Nature Reviews Cancer.

[51]  S. Takasawa,et al.  The effect of mesenchymal stem cell osteoblastic differentiation on the mechanical properties of engineered bone-like tissue. , 2011, Tissue engineering. Part A.

[52]  F Peyrin,et al.  Kinetics of in vivo bone deposition by bone marrow stromal cells within a resorbable porous calcium phosphate scaffold: An X‐ray computed microtomography study , 2007, Biotechnology and bioengineering.

[53]  Elizabeth L. Hedberg-Dirk,et al.  Synthesis and electrospun fiber mats of low Tg poly(propylene fumerate‐co‐propylene maleate) , 2010 .

[54]  Antonios G Mikos,et al.  Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model. , 2009, Tissue engineering. Part A.

[55]  Sanjay Kumar,et al.  Therapeutic potential of adult bone marrow‐derived mesenchymal stem cells in diseases of the skeleton , 2010, Journal of cellular biochemistry.

[56]  A. Bandyopadhyay,et al.  Understanding in vivo response and mechanical property variation in MgO, SrO and SiO₂ doped β-TCP. , 2011, Bone.

[57]  F. Guillemot,et al.  Role of vascular endothelial growth factor in the communication between human osteoprogenitors and endothelial cells , 2009, Journal of cellular biochemistry.

[58]  Samantha J. Polak,et al.  The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity. , 2010, Acta biomaterialia.

[59]  J. Jansen,et al.  An electrospun degradable scaffold based on a novel hydrophilic polyester for tissue-engineering applications. , 2011, Macromolecular bioscience.

[60]  Dai Fukumura,et al.  Engineering vascularized tissue , 2005, Nature Biotechnology.

[61]  David Hui,et al.  A critical review on polymer-based bio-engineered materials for scaffold development , 2007 .

[62]  Julian R Jones,et al.  Optimising bioactive glass scaffolds for bone tissue engineering. , 2006, Biomaterials.

[63]  Fergal J O'Brien,et al.  The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. , 2010, Biomaterials.

[64]  Qingshan Chen,et al.  Cross-linking Characteristics and Mechanical Properties of an Injectable Biomaterial Composed of Polypropylene Fumarate and Polycaprolactone Co-polymer , 2011, Journal of biomaterials science. Polymer edition.

[65]  T. Guise,et al.  The role of TGF-β in bone metastasis: novel therapeutic perspectives. , 2012, BoneKEy reports.

[66]  J. Tramper,et al.  Oxygen gradients in tissue‐engineered Pegt/Pbt cartilaginous constructs: Measurement and modeling , 2004, Biotechnology and bioengineering.

[67]  Fuzhai Cui,et al.  Repair of rat cranial bone defects with nHAC/PLLA and BMP‐2‐related peptide or rhBMP‐2 , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[68]  M. Edirisinghe,et al.  A novel method of selecting solvents for polymer electrospinning , 2010 .

[69]  P. Vermette,et al.  Scaffold vascularization: a challenge for three-dimensional tissue engineering. , 2010, Current medicinal chemistry.

[70]  A. Tomsia,et al.  Three-dimensional visualization of bioactive glass-bone integration in a rabbit tibia model using synchrotron X-ray microcomputed tomography. , 2011, Tissue engineering. Part A.

[71]  Peter X Ma,et al.  Biomimetic nanofibrous scaffolds for bone tissue engineering. , 2011, Biomaterials.

[72]  Di Chen,et al.  The BMP signaling and in vivo bone formation. , 2005, Gene.

[73]  Dietmar W Hutmacher,et al.  Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. , 2004, Trends in biotechnology.

[74]  M. Menger,et al.  Temporal and spatial vascularization patterns of unions and nonunions: role of vascular endothelial growth factor and bone morphogenetic proteins. , 2012, The Journal of bone and joint surgery. American volume.

[75]  A. Leusink,et al.  In vivo evaluation of highly macroporous ceramic scaffolds for bone tissue engineering. , 2009, Journal of biomedical materials research. Part A.

[76]  Anthony Atala,et al.  Principals of neovascularization for tissue engineering. , 2002, Molecular aspects of medicine.

[77]  A. Bandyopadhyay,et al.  Polycaprolactone coated porous tricalcium phosphate scaffolds for controlled release of protein for tissue engineering. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[78]  E. Willbold,et al.  Biodegradable magnesium scaffolds: Part II: peri-implant bone remodeling. , 2007, Journal of biomedical materials research. Part A.

[79]  M. Montjovent,et al.  UvA-DARE ( Digital Academic Repository ) VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo , 2010 .