Alginate composites for bone tissue engineering: a review.

Bone is a complex and hierarchical tissue consisting of nano hydroxyapatite and collagen as major portion. Several attempts have been made to prepare the artificial bone so as to replace the autograft and allograft treatment. Tissue engineering is a promising approach to solve the several issues and is also useful in the construction of artificial bone with materials including polymer, ceramics, metals, cells and growth factors. Composites consisting of polymer-ceramics, best mimic the natural functions of bone. Alginate, an anionic polymer owing enormous biomedical applications, is gaining importance particularly in bone tissue engineering due to its biocompatibility and gel forming properties. Several composites such as alginate-polymer (PLGA, PEG and chitosan), alginate-protein (collagen and gelatin), alginate-ceramic, alginate-bioglass, alginate-biosilica, alginate-bone morphogenetic protein-2 and RGD peptides composite have been investigated till date. These alginate composites show enhanced biochemical significance in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, alkaline phosphatase increase, excellent mineralization and osteogenic differentiation. Hence, alginate based composite biomaterials will be promising for bone tissue regeneration. This review will provide a broad overview of alginate preparation and its applications towards bone tissue engineering.

[1]  K. Chennazhi,et al.  Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration. , 2012, Carbohydrate polymers.

[2]  Ira Bhatnagar,et al.  Chitosan-amylopectin/hydroxyapatite and chitosan-chondroitin sulphate/hydroxyapatite composite scaffolds for bone tissue engineering. , 2012, International journal of biological macromolecules.

[3]  David J Mooney,et al.  An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. , 2011, Biomaterials.

[4]  E D Pellegrino,et al.  The chemical anatomy of bone. I. A comparative study of bone composition in sixteen vertebrates. , 1969, The Journal of bone and joint surgery. American volume.

[5]  Karim Senni,et al.  Marine Polysaccharides: A Source of Bioactive Molecules for Cell Therapy and Tissue Engineering , 2011, Marine drugs.

[6]  Hong-Ru Lin,et al.  Porous alginate/hydroxyapatite composite scaffolds for bone tissue engineering: preparation, characterization, and in vitro studies. , 2004, Journal of biomedical materials research. Part B, Applied biomaterials.

[7]  Christian Hellmich,et al.  Bone fibrillogenesis and mineralization: quantitative analysis and implications for tissue elasticity. , 2011, Journal of theoretical biology.

[8]  Seung Jin Lee,et al.  Electrospinning of polysaccharides for regenerative medicine. , 2009, Advanced drug delivery reviews.

[9]  T. Uemura,et al.  Synthesis and in vivo evaluation of a novel hydroxyapatite/collagen–alginate as a bone filler and a drug delivery carrier of bone morphogenetic protein , 2004 .

[10]  Yimin Qin,et al.  Alginate fibres: an overview of the production processes and applications in wound management , 2008 .

[11]  E. Brien,et al.  Bone grafting alternatives for cavitary defects in children , 2013 .

[12]  J. Venkatesan,et al.  Stimulation of minerals by carbon nanotube grafted glucosamine in mouse mesenchymal stem cells for bone tissue engineering. , 2012, Journal of biomedical nanotechnology.

[13]  C. Perka,et al.  Optimization of bone engineering by means of growth factors in a three-dimensional matrix. , 2003, Journal of biomedical materials research. Part A.

[14]  A. Lode,et al.  Synthesis and physicochemical, in vitro and in vivo evaluation of an anisotropic, nanocrystalline hydroxyapatite bisque scaffold with parallel‐aligned pores mimicking the microstructure of cortical bone , 2015, Journal of tissue engineering and regenerative medicine.

[15]  P. Ma,et al.  Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1. Structure, gelation rate and mechanical properties. , 2001, Biomaterials.

[16]  Toshihide Nakashima,et al.  Review Peripheral nerve regeneration using non-tubular alginate gel crosslinked with covalent bonds , 2005, Journal of materials science. Materials in medicine.

[17]  Wen He,et al.  Research progress on chemical modification of alginate: A review , 2011 .

[18]  C. Wiegand,et al.  Comparative in vitro study on cytotoxicity, antimicrobial activity, and binding capacity for pathophysiological factors in chronic wounds of alginate and silver‐containing alginate , 2009, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[19]  Xufeng Niu,et al.  Preparation and characterization of an injectable composite , 2009, Journal of materials science. Materials in medicine.

[20]  E. Brey,et al.  The effect of FGF-1 loaded alginate microbeads on neovascularization and adipogenesis in a vascular pedicle model of adipose tissue engineering. , 2010, Biomaterials.

[21]  Shantikumar V. Nair,et al.  Biomedical applications of chitin and chitosan based nanomaterials—A short review , 2010 .

[22]  D. Kohane,et al.  Engineering vascularized skeletal muscle tissue , 2005, Nature Biotechnology.

[23]  Geunhyung Kim,et al.  Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration , 2013, Bioprocess and Biosystems Engineering.

[24]  R. Shelton,et al.  Comparison of bone marrow cell growth on 2D and 3D alginate hydrogels , 2005, Journal of materials science. Materials in medicine.

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

[26]  Richard M. Shelton,et al.  Evaluation of sodium alginate for bone marrow cell tissue engineering. , 2003, Biomaterials.

[27]  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.

[28]  Miqin Zhang,et al.  Chitosan-alginate hybrid scaffolds for bone tissue engineering. , 2005, Biomaterials.

[29]  Anthony P. Hollander,et al.  Biopolymer methods in tissue engineering , 2003 .

[30]  Chaenyung Cha,et al.  Integrative design of a poly(ethylene glycol)-poly(propylene glycol)-alginate hydrogel to control three dimensional biomineralization. , 2011, Biomaterials.

[31]  Jayachandran Venkatesan,et al.  Preparation and characterization of carbon nanotube-grafted-chitosan – Natural hydroxyapatite composite for bone tissue engineering , 2011 .

[32]  P Zioupos,et al.  Mechanical properties and the hierarchical structure of bone. , 1998, Medical engineering & physics.

[33]  G. Turco,et al.  Nano-composite scaffolds for bone tissue engineering containing silver nanoparticles: preparation, characterization and biological properties , 2013, Journal of Materials Science: Materials in Medicine.

[34]  Z. Xiong,et al.  Bone tissue engineering using bone marrow stromal cells and an injectable sodium alginate/gelatin scaffold. , 2012, Journal of biomedical materials research. Part A.

[35]  Horia Iovu,et al.  Sodium alginate/graphene oxide composite films with enhanced thermal and mechanical properties. , 2013, Carbohydrate polymers.

[36]  Seog-Young Yoon,et al.  In vivo evaluation of porous hydroxyapatite/chitosan-alginate composite scaffolds for bone tissue engineering. , 2012, International journal of biological macromolecules.

[37]  Y. Suzuki,et al.  Reconstruction of rat peripheral nerve gap without sutures using freeze-dried alginate gel. , 2000, Journal of biomedical materials research.

[38]  R. Bareille,et al.  The effect of the co-immobilization of human osteoprogenitors and endothelial cells within alginate microspheres on mineralization in a bone defect. , 2009, Biomaterials.

[39]  Carl G Simon,et al.  Strong calcium phosphate cement-chitosan-mesh construct containing cell-encapsulating hydrogel beads for bone tissue engineering. , 2006, Journal of biomedical materials research. Part A.

[40]  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.

[41]  U. Bogdahn,et al.  The promotion of oriented axonal regrowth in the injured spinal cord by alginate-based anisotropic capillary hydrogels. , 2006, Biomaterials.

[42]  S. Chang,et al.  Cranial repair using BMP-2 gene engineered bone marrow stromal cells. , 2004, The Journal of surgical research.

[43]  S. Sarvanan,et al.  Biocomposite scaffolds containing chitosan/alginate/nano-silica for bone tissue engineering. , 2013, Colloids and surfaces. B, Biointerfaces.

[44]  Scott J Hollister,et al.  Controlled nucleation of hydroxyapatite on alginate scaffolds for stem cell-based bone tissue engineering. , 2010, Journal of biomedical materials research. Part A.

[45]  Tommasina Coviello,et al.  Polysaccharide hydrogels for modified release formulations. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[46]  M. Farina,et al.  Hydroxyapatite-alginate biocomposite promotes bone mineralization in different length scales in vivo , 2009 .

[47]  Hongzhi Zhou,et al.  Gas-foaming calcium phosphate cement scaffold encapsulating human umbilical cord stem cells. , 2012, Tissue engineering. Part A.

[48]  J. L. López-Lacomba,et al.  In vivo comparison of the effects of rhBMP-2 and rhBMP-4 in osteochondral tissue regeneration. , 2010, European cells & materials.

[49]  D. Irvine,et al.  Modular injectable matrices based on alginate solution/microsphere mixtures that gel in situ and co-deliver immunomodulatory factors. , 2008, Acta biomaterialia.

[50]  Francesco Brun,et al.  Alginate/Hydroxyapatite biocomposite for bone ingrowth: a trabecular structure with high and isotropic connectivity. , 2009, Biomacromolecules.

[51]  Jayachandran Venkatesan,et al.  Preparation and characterization of chitosan-carbon nanotube scaffolds for bone tissue engineering. , 2012, International journal of biological macromolecules.

[52]  Naotoshi Nakashima,et al.  Preparation of carbon nanotube-alginate nanocomposite gel for tissue engineering. , 2006, Dental materials journal.

[53]  K. Edgar,et al.  Alginate esters via chemoselective carboxyl group modification. , 2013, Carbohydrate polymers.

[54]  W. Saltzman,et al.  Controlled delivery of VEGF via modulation of alginate microparticle ionic crosslinking. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[55]  Eben Alsberg,et al.  Engineering growing tissues , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Stephen J. Florczyk,et al.  Enhanced bone tissue formation by alginate gel-assisted cell seeding in porous ceramic scaffolds and sustained release of growth factor. , 2012, Journal of biomedical materials research. Part A.

[57]  M. Tanihara,et al.  Sustained release of basic fibroblast growth factor and angiogenesis in a novel covalently crosslinked gel of heparin and alginate. , 2001, Journal of biomedical materials research.

[58]  Y. Lee,et al.  Electrospun scaffolds composing of alginate, chitosan, collagen and hydroxyapatite for applying in bone tissue engineering , 2013 .

[59]  H. Kim,et al.  Core-shell designed scaffolds of alginate/alpha-tricalcium phosphate for the loading and delivery of biological proteins. , 2013, Journal of biomedical materials research. Part A.

[60]  G. Pelled,et al.  Polymer‐encapsulated engineered adult mesenchymal stem cells secrete exogenously regulated rhBMP‐2, and induce osteogenic and angiogenic tissue formation , 2002 .

[61]  Mario Malinconico,et al.  Marine Derived Polysaccharides for Biomedical Applications: Chemical Modification Approaches , 2008, Molecules.

[62]  T. Anada,et al.  Octacalcium phosphate-precipitated alginate scaffold for bone regeneration. , 2009, Tissue engineering. Part A.

[63]  M. Rinaudo,et al.  Main properties and current applications of some polysaccharides as biomaterials , 2008 .

[64]  Yongxiang Luo,et al.  Hierarchical mesoporous bioactive glass/alginate composite scaffolds fabricated by three-dimensional plotting for bone tissue engineering , 2012, Biofabrication.

[65]  M. H. Nazarpak.  Preparation and evaluation of porous alginate/ hydroxyapatite composite scaffold coated with a biodegradable triblock copolymer , 2013 .

[66]  Stephen J. Florczyk,et al.  Evaluation of three-dimensional porous chitosan-alginate scaffolds in rat calvarial defects for bone regeneration applications. , 2013, Journal of biomedical materials research. Part A.

[67]  K. Edgar,et al.  Chemical modification of alginates in organic solvent systems. , 2011, Biomacromolecules.

[68]  Jiang Chang,et al.  The calcium silicate/alginate composite: preparation and evaluation of its behavior as bioactive injectable hydrogels. , 2013, Acta biomaterialia.

[69]  Eben Alsberg,et al.  Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells. , 2004, Bone.

[70]  Malcolm L Snead,et al.  Co-encapsulation of anti-BMP2 monoclonal antibody and mesenchymal stem cells in alginate microspheres for bone tissue engineering. , 2013, Biomaterials.

[71]  Jiandong Ye,et al.  Alginate/poly (lactic-co-glycolic acid)/calcium phosphate cement scaffold with oriented pore structure for bone tissue engineering. , 2009, Journal of biomedical materials research. Part A.

[72]  M. Abdouss,et al.  A hydrophobically-modified alginate gel system: utility in the repair of articular cartilage defects , 2011, Journal of materials science. Materials in medicine.

[73]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[74]  Wei Tang,et al.  Bone regeneration by BMP-2 enhanced adipose stem cells loading on alginate gel , 2008, Histochemistry and Cell Biology.

[75]  Shingo Nakamura,et al.  Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings. , 2010, Biomaterials.

[76]  J. Leong,et al.  In vitro evaluation of alginate encapsulated adipose-tissue stromal cells for use as injectable bone graft substitute. , 2006, Biochemical and biophysical research communications.

[77]  Ferdous Khan,et al.  Polysaccharides and their derivatives for versatile tissue engineering application. , 2013, Macromolecular bioscience.

[78]  Bikramjit Basu,et al.  Physical and cytocompatibility properties of bioactive glass–polyvinyl alcohol–sodium alginate biocomposite foams prepared via sol–gel processing for trabecular bone regeneration , 2009, Journal of materials science. Materials in medicine.

[79]  Qingling Feng,et al.  Thermo-sensitive alginate-based injectable hydrogel for tissue engineering , 2012 .

[80]  Zhibing Zhang,et al.  Viscoelastic properties of mineralized alginate hydrogel beads , 2012, Journal of Materials Science: Materials in Medicine.

[81]  Q. Feng,et al.  In vitro and in vivo degradation of an injectable bone repair composite , 2010 .

[82]  J. Weng,et al.  Synthesis of an RGD-grafted oxidized sodium alginate-N-succinyl chitosan hydrogel and an in vitro study of endothelial and osteogenic differentiation. , 2013, Journal of materials chemistry. B.

[83]  Mário A. Barbosa,et al.  Polysaccharides as scaffolds for bone regeneration , 2005 .

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

[85]  Andrés J. García,et al.  Effects of protein dose and delivery system on BMP-mediated bone regeneration. , 2011, Biomaterials.

[86]  Christian Hellmich,et al.  Ductile sliding between mineral crystals followed by rupture of collagen crosslinks: experimentally supported micromechanical explanation of bone strength. , 2009, Journal of theoretical biology.

[87]  A. Boccaccini,et al.  Electrophoretic deposition of chitosan/45S5 Bioglass® composite coatings for orthopaedic applications , 2011 .

[88]  Masayoshi Ohta,et al.  Alginate enhances elongation of early regenerating axons in spinal cord of young rats. , 2004, Tissue engineering.

[89]  K. Chennazhi,et al.  Development of a phytochemical scaffold for bone tissue engineering using Cissus quadrangularis extract , 2012 .

[90]  D J Mooney,et al.  Alginate hydrogels as synthetic extracellular matrix materials. , 1999, Biomaterials.

[91]  Ki Suk Park,et al.  Chondrogenic differentiation of bone marrow stromal cells in transforming growth factor-β1 loaded alginate bead , 2005 .

[92]  J. Brinchmann,et al.  Phenotype and gene expression of human mesenchymal stem cells in alginate scaffolds. , 2009, Tissue engineering. Part A.

[93]  R. Pallela,et al.  Biophysicochemical evaluation of chitosan-hydroxyapatite-marine sponge collagen composite for bone tissue engineering. , 2012, Journal of biomedical materials research. Part A.

[94]  V. Lozinsky,et al.  Coupling of gelatin to inner surfaces of pore walls in spongy alginate-based scaffolds facilitates the adhesion, growth and differentiation of human bone marrow mesenchymal stromal cells , 2011, Journal of materials science. Materials in medicine.

[95]  Huaping Tan,et al.  Alginate-Based Biomaterials for Regenerative Medicine Applications , 2013, Materials.

[96]  Juan Wang,et al.  Injectable calcium phosphate-alginate-chitosan microencapsulated MC3T3-E1 cell paste for bone tissue engineering in vivo. , 2013, Materials science & engineering. C, Materials for biological applications.

[97]  B. Diehl-seifert,et al.  Alginate/silica composite hydrogel as a potential morphogenetically active scaffold for three-dimensional tissue engineering , 2013 .

[98]  H. Fan,et al.  Biomimetic interpenetrating polymer network hydrogels based on methacrylated alginate and collagen for 3D pre-osteoblast spreading and osteogenic differentiation , 2012 .

[99]  L. Yao,et al.  Culture of Neural Stem Cells in Calcium Alginate Beads , 2006, Biotechnology progress.

[100]  Christian Hellmich,et al.  'Universal' microstructural patterns in cortical and trabecular, extracellular and extravascular bone materials: micromechanics-based prediction of anisotropic elasticity. , 2007, Journal of theoretical biology.

[101]  Sidney Lees,et al.  Mineralization of type I collagen. , 2003, Biophysical journal.

[102]  Athanasios Mantalaris,et al.  The use of murine embryonic stem cells, alginate encapsulation, and rotary microgravity bioreactor in bone tissue engineering. , 2009, Biomaterials.

[103]  C. Werner.  Polymers for Regenerative Medicine , 2010 .

[104]  M. Gelinsky,et al.  Scaffolds for Hard Tissue Engineering by Ionotropic Gelation of Alginate-Influence of Selected Preparation Parameters , 2007 .

[105]  Aixi Yu,et al.  Bone marrow mesenchymal stem cells combined with calcium alginate gel modified by hTGF-β1 for the construction of tissue-engineered cartilage in three-dimensional conditions , 2012, Experimental and therapeutic medicine.

[106]  K. Chennazhi,et al.  Fabrication of alginate/nanoTiO2 needle composite scaffolds for tissue engineering applications , 2011 .

[107]  B. Nies,et al.  RGD-peptides for tissue engineering of articular cartilage. , 2002, Biomaterials.

[108]  D. Mooney,et al.  Study on the potential of RGD- and PHSRN-modified alginates as artificial extracellular matrices for engineering bone , 2013, Journal of Artificial Organs.

[109]  C. Hellmich,et al.  Average hydroxyapatite concentration is uniform in the extracollagenous ultrastructure of mineralized tissues: evidence at the 1–10-μm scale , 2003, Biomechanics and modeling in mechanobiology.

[110]  Rui L. Reis,et al.  Wettability Influences Cell Behavior on Superhydrophobic Surfaces with Different Topographies , 2012, Biointerphases.

[111]  Miqin Zhang,et al.  Influence of processing parameters on pore structure of 3D porous chitosan-alginate polyelectrolyte complex scaffolds. , 2011, Journal of biomedical materials research. Part A.

[112]  K W Anderson,et al.  Cell-interactive Alginate Hydrogels for Bone Tissue Engineering , 2001, Journal of dental research.

[113]  David J Mooney,et al.  Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix. , 2007, Biomaterials.

[114]  B. Fuller,et al.  Cryopreservation of alginate encapsulated mesenchymal stromal cells. , 2013, Cryobiology.

[115]  S. Shi,et al.  Alginate hydrogel as a promising scaffold for dental-derived stem cells: an in vitro study , 2012, Journal of Materials Science: Materials in Medicine.

[116]  R. Soares,et al.  Immobilization of human mesenchymal stem cells within RGD-grafted alginate microspheres and assessment of their angiogenic potential. , 2010, Biomacromolecules.

[117]  K. Fröberg,et al.  A structural approach to bone adhering of bioactive glasses , 1989 .

[118]  Kevin J Edgar,et al.  Alginate derivatization: a review of chemistry, properties and applications. , 2012, Biomaterials.

[119]  E. Alsberg,et al.  The effect of oxidation on the degradation of photocrosslinkable alginate hydrogels. , 2012, Biomaterials.

[120]  Miqin Zhang,et al.  Alginate‐Based Nanofibrous Scaffolds: Structural, Mechanical, and Biological Properties , 2006 .

[121]  F. Gu,et al.  Sustained delivery of vascular endothelial growth factor with alginate beads. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[122]  M. Alonso-Sande,et al.  Evaluation of Alginate and Hyaluronic Acid for Their Use in Bone Tissue Engineering , 2012 .

[123]  H. Kim,et al.  Alginate combined calcium phosphate cements: mechanical properties and in vitro rat bone marrow stromal cell responses , 2011, Journal of materials science. Materials in medicine.

[124]  A. Jayakrishnan,et al.  Evaluation of the effect of incorporation of dibutyryl cyclic adenosine monophosphate in an in situ-forming hydrogel wound dressing based on oxidized alginate and gelatin. , 2006, Biomaterials.

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

[126]  Eben Alsberg,et al.  Photocrosslinked alginate hydrogels with tunable biodegradation rates and mechanical properties. , 2009, Biomaterials.

[127]  K. Chennazhi,et al.  Sodium alginate/poly(vinyl alcohol)/nano ZnO composite nanofibers for antibacterial wound dressings. , 2011, International journal of biological macromolecules.

[128]  Seeram Ramakrishna,et al.  Nanofibrous structured biomimetic strategies for skin tissue regeneration , 2013, Wound Repair and Regeneration.

[129]  Stephanie Lucas,et al.  Fibroblast growth factor-1 (FGF-1) loaded microbeads enhance local capillary neovascularization. , 2010, The Journal of surgical research.

[130]  Tim Miller,et al.  Continuous Delivery of Stromal Cell-Derived Factor-1 from Alginate Scaffolds Accelerates Wound Healing , 2010, Cell transplantation.

[131]  David J Mooney,et al.  Alginate hydrogels as biomaterials. , 2006, Macromolecular bioscience.

[132]  K. Chennazhi,et al.  Biocompatible conducting chitosan/polypyrrole-alginate composite scaffold for bone tissue engineering. , 2013, International journal of biological macromolecules.

[133]  K. Nakanishi,et al.  Apatite Formation Induced by Silica Gel in a Simulated Body Fluid , 1992 .