Scaffolds for Bone Regeneration

Melba Navarro, Josep A Planell
TouchMusculoskeletal.com; november 2011 - Online only
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Abstract

Regenerative medicine, and particularly tissue engineering, has emerged in recent years as a potential alternative solution to tissue transplantation and grafting. Tissue engineering covers the repair and regeneration of organs and tissues using the triad of cells, biochemical signals and scaffolds. in this area, the design of 3D temporary supports that carefully consider the most influential factors in the regeneration process is required. This article provides a complete overview of the most common currently used biomaterials and techniques for the fabrication of 3D porous structures, and also considers the different approaches used to enhance bone regeneration.
Keywords
scaffolds, tissue engineering, bone, biomaterials, 3D porous structures
Disclosure The authors have no conflicts of interest to declare.
Received: October 12, 2011 Accepted November 04, 2011
Correspondence: Melba navarro, c/Baldiri reixac 10-12, 08028 Barcelona. e: mnavarro@ibecbarcelona.eu

Tissue regeneration and regenerative medicine in general have appeared in recent years as the best solution to a large number of organic malfunctions, diseases or trauma. Tissue engineering has emerged as a potential alternative solution to tissue transplantation and grafting. Allografts, autografts and xenografts present several known limitations, such as donor-site scarcity, rejection, disease transfer, harvesting costs and post-operative morbidity.1–3 Both tissue engineering and regenerative medicine look at the repair and regeneration of organs and tissues using natural signalling pathways and components such as stem cells, growth factors and peptide sequences, among others, in combination with synthetic scaffolds, which usually consist of degradable biomaterials.4 Probably the key issue when trying to engineer the regeneration process is comprehension of the dialogue between cells and their microenvironment. The basis for this comprehension is that environmental biochemical and biophysical cues and signals are translated by cells into intracellular commands that activate specific events in response to such signals and that make cells modify their behaviour to react with appropriate responses. of the multiple elements that participate in this dialogue and affect the regenerative process, it is necessary to consider the following:

  • transport of oxygen, electrolytes, nutrients and molecules to the cells;
  • cell migration and mobility towards the regeneration site and within it;
  • the metabolic environment that will be responsible for the degradation of the implanted devices;
  • cell–material interactions, where material surface properties have a direct and strong effect on cell behaviour;
  • biochemical and biophysical stimuli from the microenvironment, such as chemical cues or mechanical stimuli that can regulate cell behaviour;
  • angiogenesis control, which is essential for the regeneration of the tissue in vivo;
  • immunological and inflammatory response; and
  • cell behaviour, including attachment, proliferation and differentiation into the right lineage.

References:
  1. Banwart Jc, Asher MA, hassanein rs, iliac crest bone graft harvest donor site morbidity. A statistical evaluation, Spine, 1995;20:1055–60.
  2. fernyhough Jc, schimandle JJ, Weigel Mc, et al., chronic donor site pain complicating bone graft harvest from the posterior iliac crest for spinal fusion, Spine, 1992;17:1474–80.
  3. goulet JA, senunas Le, Desilva gL, greengield ML, Autogenous iliac crest bone graft. complications and functional assessment, Clin Orthop, 1997;339:76–81.
  4. hardouin P, Anselme k, flautre B, et al., Tissue engineering and skeletal diseases, Joint Bone Spine, 2000;67:419–24.
  5. navarro M, Michiardi A, The challenge of combining cells, synthetic materials and growth factors to engineer bone tissue. in: Barnes sJ, harris LP (eds), Tissue Engineering: Roles, Materials and Applications, nY: nova science Publisher inc, 2008;19–66.
  6. Boccaccini Ar, roether JA, hench LL, et al., A composite approach to tissue engineering, Ceram Eng Sci Proc, 2002;23:805–16.
  7. spaans cJ, Belgraver VW, rienstra o, et al., solvent-free fabrication of micro-porous polyurethane amide and polyurethane-urea scaffolds for repair and replacement of the knee-joint meniscus, Biomaterials, 2000;21:2453–60.
  8. hench L, Polak J, Third generation biomedical materials, Science, 2002;295:1014–17.
  9. seal BL, oteroTc, Panitch A, Polymeric biomaterials for tissue and organ regeneration, Mater Sci Eng: R: Rep, 2001;34:147–230.
  10. chen gQ, Wu Q, Polyhydroxyalkanoates as tissue engineering materials, Biomaterials, 2005;26:6565–78.
  11. Middleton Jc, Tipton AJ, synthetic biodegradable polymers as orthopedic devices, Biomaterials, 2000;21:2335–46.
  12. Zhang Xh, reagan Mr, kaplan DL, electrospun silk biomaterial scaffolds for regenerative medicine, Adv Drug Deliv Rev, 2009;61:988–1006
  13. Zhang Yf, Wu cT, fris T, Xiao Y, The osteogenic properties of caP/silk composite scaffolds, Biomaterials, 2010;31:2848–56.
  14. Duarte Arc, Mano Jf, reis rL, novel 3D scaffolds of chitosan-PLLA blends for tissue engineering applications: Preparation and characterization, J Supercrit Fluids, 2010;54:282–9.
  15. Li Lh, kommareddy kP, Pilz c, et al., in vitro bioactivity of bioresorbable porous polymeric scaffolds incorporating hydroxyapatite microspheres, Acta Biomaterialia, 2010;6:2525–31.
  16. caplanis n, Lee MB, Zimmerman gJ, et al., effect of allogeneic freezedried demineralized bone matrix on regeneration of alveolar bone and periodontal attachment in dogs, J Clin Periodontol, 1998;25:801–6.
  17. groeneveld ehJ, van den Bergh JPA, holzmann P, et al., Mineralization processes in demineralized bone matrix grafts in human maxillary sinus floor elevations, J Biomed Mater Res, 1999;48:393–402.
  18. russell JL, Block Je, clinical utility of demineralized bone matrix for osseous defects, arthrodesis, and reconstruction:impact of processing techniques and study methodology, Orthopedics, 1999;22:524–31.
  19. Wang Jc, Alanay A, Mark D, kanim Le, et al., A comparison of commercially available demineralised bone matrix for spinal fusion, Eur Spine J, 2007;16:1233–40.
  20. canter hi, Vargel i, Mavili Me, reconstruction of mandibular defects using autografts combined with demineralized bonematrix and cancellous allograft, J Craniofac Surg, 2007;18:95–100.
  21. Peel sAf, hu ZM, clokie cML, in search of the ideal bone morphogenetic protein delivery system: in vitro studies on demineralized bone matrix, purified, and recombinant bone morphogenetic protein, J Craniofac Surg, 2003;14:284–91.
  22. ferraz MP, Monteiro fJ, Manuel cM, hydroxyapatite nanoparticles: a review of preparation methodologies, J ApplBiomater Biomec, 2004;2:74–80.
  23. Tampieri A, celotti g, sprio s, et al., Porosity-graded hydroxyapatiteceramics to replace natural bone, Biomaterials,2001;22:1365–70.
  24. furuichi k, oaki Y, ichimiya h, et al., Preparation of hierarchically organized calcium phosphate-organic polymer composites by calcification of hydrogel, Sci Technol Adv Mater, 2006;7:219–25.
  25. Aizawa M, Porter Ae, Best sM, Bonfield W, ultrastructural observation of single-crystal apatite fibers, Biomaterials, 20095;26:3427–33.
  26. he X, ge X, Liu h, Wang M, Zhang Z, cagelike polymer microspheres with hollow core/porous shell structures,J Polym Sci A: Polym Chem, 2007;45:933–41.
  27. shi XT, ren L, Tian M, et al., in vivo and in vitro osteogenesis of ítem cells induced by controlled release of drugs frommicrospherical scaffolds, J Mater Chem, 2010;20:9140–8.
  28. Weir MD, Xu hhk, human bone marrow stem cellencapsulating calcium phosphate scaffolds for bone repair, Acta Biomaterialia, 2010;6:4118–26.
  29. Almirall A, Larrecq g, Delgado JA, et al., fabrication of low temperature macroporous hydroxypapatite scaffolds byfoaming and hydrolysis of an alpha-TcP paste, Biomaterials, 2004;25:3671–80.
  30. ginebra MP, Delgado JA, harr i, et al., factors affecting the structure and properties of an injectable self-setting calcium phosphate foam, J Biomed Mater Res A, 2007;80:351–61.
  31. gong WL, Abdelouas A, Lutze W, Porous bioactive glass and glass–ceramics made by reaction sintering under pressure, J Biomed Mater Res, 2001;54:320–7.
  32. navarro M, Del Valle s, Martínez s, et al., new macroporous calcium phosphate glass ceramic for guided bone regeneration, Biomaterials, 2004;25:4233–41.
  33. Yuan hP, de Bruijn JD, Zhang XD, et al., Bone induction by porous glass ceramic made from bioglass (45s5), J Biomed Mater Res, 2001;58:270–6.
  34. navarro M, ginebra MP, Planell JA, et al., in vitro degradation behavior of a novel bioresorbable composite material based on PLA and a soluble caP glass, Acta Biomater, 2005;1:411–9.
  35. navarro M, Aparicio c, charles-harris M, et al., Development of a biodegradable composite scaffold for bone tissue engineering: Physicochemical, topographical, mechanical , degradation, and biological properties, Adv Polym Sci, 2006;200:209–31.
  36. Liao ss, Wang W, uo M, et al., A three-layered nano-carbonated hydroxyapatite/collagen/PLgA composite membrane for guided tissue regeneration, Biomaterials, 2005;26:7564–71.
  37. Li Z, Yubao L, Aiping Y, et al., Preparation and in vitro investigation of chitosan/nano-hydroxyapatite composite used as bone substitute materials, J Mater Sci Mater Med,2005;16:213–9.
  38. Taito T, Myoui A, Takaoka k, et al., Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-Peg/hydroxyapatite composite, Biomaterials, 2005;26:73–9.
  39. McManus AJ, Doremus rh, siegel rW, Bizios r, evaluation of cytocompatibility and bending modulus of nanoceramic/polymer composites, J Biomed Mater Res A, 2005;72:98–106.
  40. rezwan k, chen QZ, Blaker JJ, Boccaccini Ar, Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering, Biomaterials, 2006;27:3413–31.
  41. hutmacher D, schantz JT, Lam cXf, et al., state of the art and future directions of scaffold-based bone engineering from a biomaterials perpective, J Tissue Eng Regen Med, 2007;1:245–60.
  42. Liao ss, cui fZ, Zhang W, feng QL, hierarchically biomimetic bone scaffold materials: nano-hA/collagen/PLA composite, J Biomed Mater Res Part B: Appl Biomater, 2004;69B:158–65.
  43. sepulveda P, Jones Jr, hench LL, bioactive sol-gel foams for tissue repair, J Biomed Mat Res, 2002;59:340–8.
  44. Wei g, Ma PX, structure and properties of nanohydroxyapatite/ polymer composite scaffolds for bone tissue engineering, Biomaterials, 2004;25:4749–57.
  45. Tsuru k, ohtsuki c, osaka A, et al., Bioactivity of sol-gel derived organically modified silicates: Part i: in vitro examination, J Mater Sci: Mater Med, 1997;8:157–61.
  46. uchino T, ohtsuki c, kamitakahara M, et al., hydroxyapatiteforming ability and mechanical properties of organic-inorganic hybrids reinforced by calcium phosphates, Journal of the Ceramic Society of Japan, 2006;114:692–6.
  47. rubin JP, Yaremchuk MJ, complications and toxicities of implantable biomaterials used in facial reconstructive and aesthetic surgery: a comprehensive review of the literature, Plast Reconstr Surg, 1997;100:1336–53.
  48. Wang XJ, Li Yc, hodgson PD, Wen c, Biomimetic modification of porous TinbZr alloy scaffold for bone tissue engineering, Tissue Engineering Part A, 2010;16:309–16.
  49. Li JP, habibovic P, van den Doel M, et al., Bone ingrowth in porous titanium implants produced by 3D fiber deposition, Biomaterials, 2007;28:2810–20.
  50. gu YW, Li h, Tay BY, et al., in vitro bioactivity and osteoblast response of porous niTi synthesized by shs using nanocrystalline ni-Ti reaction agent, J Biomed Mater Res, 2006;78:316–23.
  51. unger re, Peters k, Assad M, et al., endothelial cell compatibility of porous nitinol, Transactions – 7th World Biomaterials Congress, 2004;1538.
  52. Levine Br, spore s, Poggie rA, et al., experimental and clinical performance of porous tantalum in orthopedic surgery, Biomaterials, 2006;27:4671–81.
  53. Arciniegas M, Aparicio c, Manero JM, gil fJ, Low elastic modulus metals for joint prosthesis: Tantalum and nickeltitanium foams, J Eur Ceram Soc, 2007;27:3391–8.
  54. Miyazaki T, kim hM, kokubo T, et al., effect of thermal treatment on apatite forming ability of naoh-treated tantalum metal, J Mater Sci: Mater Med, 2001;12:683–7.
  55. Wen ce, Mabuchi M, Yamada Y, et al., Processing of biocompatible porous Ti and Mg, Scr Mater, 2001;45:1147–53.
  56. Witte f, ulrico h, rudert M, Willbold e, Biodegradable magnesium scaffolds: Part 1: appropriate inflammatory response, J Biomed Mater res A, 2007;81:748–56.
  57. coombes AgA, heckman JD, gel casting of resorbable polymers: 1. Processing and applications, Biomaterials , 1992;13:217–24.
  58. Mikos Ag, sarakinos g, Leite sM, et al., Laminated threedimensional biodegradable foams for use in tissueengineering, Biomaterials, 1993;14:323–30.
  59. Mooney DJ, Baldwin Df, suh nP, et al., novel approach to fabricate porous sponges of poly (D,L-lactic-co-glycolic acid) without the use of organic solvents, Biomaterials, 1996;17:1417–22.
  60. Wake Mc, gupta Pk, Mikos Ag, fabrication of pliable biodegradable polymer foams to engineer soft tissues, Cell Transplant, 1996;5:465–73.
  61. ge Z, Jin Z, cao T, Manufacture of degradable polymeric scaffolds for bone regeneration, Biomed Mater, 2008;3:1–11.
  62. hollister s, Porous scaffold design for tissue engineering, Nat Materials, 2005;4:518–24.
  63. Yang s, Leong k, Du Z, chua c, The design of scaffolds for use in tissue engineering. Part i. Traditional factors, TissueEng, 2001;7:679–89.
  64. Peltola sM, Melchels fPW, grijpma DW, kellomäki M, A review of rapid prototyping techniques for tissue engineering purposes, Ann Med, 2008;40:268–80.
  65. Teixeira s, fernandes Mh, ferraz MP, Monteiro fJ, Proliferation and mineralization of bone marrow cells cultured on macroporous hydroxyapatite scaffolds functionalized with collagen type i for bone tissue regeneration, J Biome Mater Res A, 2010;95:1–8.
  66. navarro M, Del Valle s, Martínez s, et al., new macroporous calcium phosphate glass ceramic for guided bone regeneration, Biomaterials, 2004;25:4233–41.
  67. español M, Perez rA, Montufar eB, et al., intrinsic porosity of calcium phosphate cements and its significance for drug delivery and tissue engineering applications, Acta Biomaterialia, 2009;5:2752–62.
  68. guo Dg, Xu kW, structure and properties of sr-containing BcP scaffolds modulated by rP porous negative mould, Rare Metal Materials and Engineering, 2010;39:530–4.
  69. klawitter JJ, hulbert sf, Application of porous ceramics for the attachment of load-bearing internal orthopaedic applications, Cell Transplant, 1971;3:339.
  70. Zeltinger J, sherwood Jk, graham DA, et al., effect of pore size and void fraction on cellular adhesion, proliferation, and matrix deposition, Tissue Eng, 2001;7:557–72.
  71. Burger eh, klein-nulend J, Mechanotransduction in bone-role of the lacunocanalicular network, FASEB J, 1999;13:s101–s112.
  72. D’Avis P, hessle h, cardenas J, et al., Potent, integrin selective rgD-containing peptides promote cell-specific dhesion on three dimensional collagen matrices, Trans Soc Biomater, 1998;XXi:100.
  73. Dee kc, Andersen TT, Bizios r, osteoblast population migration characteristics on substrates modified with immobilized adhesive peptides, Biomaterials, 1999;20:221–7.
  74. garcia AJ, Ducheyne P, Boettiger D, cell adhesion strength increases linearly with absorbed fibronectin surface density, Tissue Eng, 1997;3:197–206.
  75. hersel u, Dahmen c, kessler h, rgD modified polymers: biomaterials for stimulated cell adhesion and beyond, Biomaterials, 2003;24:4385–415.
  76. Palmer Lc, newcomb cJ, kaltz sr, et al., Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel, Chem Rev, 2008;108:4754–83.
  77. nathan D, sporn M, cytokines in context, J Cell Biol, 1991;113:981–6.
  78. ripamonti u, Tasker Jr, Advances in biotechnology for tissue engineering of bone, curr Phar, Biotechnol, 2000;1:47–55.
  79. rodríguez-cabello Jc, Prieto s, reguera J, et al., Biofunctional design of elastin-like polymers for advanced applications in nanobiotechnology, J Biomater Sci Polym Ed, 2007;18:269–86.
  80. sargeant TD, rao Ms, koh cY, stupp si, covalent functionalization on niTi surfaces with bioactive peptide amphiphile nanofibers, Biomaterials, 2008;29:1085–98.
  81. nukavarapu Ps, kumbar sg, Brown JL, et al., Polyphosphazene/nano-hydroxyapatite composite microsphere scaffolds for bone tissue engineering, Biomacromolecules, 2008;8:1818–25.
  82. Laurencin cT, kumbar sg, nukavaparu sP, nanotechnology and orthopedics: a personal perspective, Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2009;1:6–10.
  83. navarro M, ginebra MP, Planell JA, et al., in vitro degradation behavior of a novel bioresorbable composite material based on PLA and a soluble caP glass, Acta Biomater, 2005;1:411–9.
  84. Misra sk, nazhat sn, Valappil sP, et al., fabrication and characterization of biodegradable Poly(3-hydroxybutyrate) composite containing Bioglass, Biomacromolecules, 2007;8:2112–9.
  85. Misra sk, Mohn D, Brunner TJ, et al., comparison of nanoscale and microscale bioactive glass on the properties of P(3hB)/bioglass composites, Biomaterials, 2008;29:1750–61.
  86. haimi s, suuriniemi n, haaparanta AM, et al., growth and osteogenic differentiation of adipose stem cells on PLA/bioactive glass and PLA/β-TcP scaffolds, Tissue Eng Part A, 2009;15:1473–80.
  87. kim hW, song Jh, kim he, nanofiber generation of gelatin– hydroxyapatite biomimetics for guided tissue regeneration, Adv Funct Mater, 2005;15:1988–94.
  88. Tuslakoglu k, Bolgen n, salgado AJ, et al., nano- and microfiber combined scaffolds: a new architecture for bone tissue engineering, J Mater Sci: Mater Med, 2005;16:1099–104.
  89. cao h, kuboyama n, A biodegradable porous composite scaffold of PgA/beta-TcP for bone tissue engineering, Bone, 2010;46:368–95.
  90. Zhang Y, Wu c, friis T, Xiao Y, osteogenic properties of caP/silk composite scaffolds, Biomaterials, 2010;31:2848–56.
  91. hasegawa s, Tamura J, neo M, et al., in vivo evaluation of a porous hydroxyapatite/poly-DL-lactide composite for use as a bone substitute, J Biomed Mater Res A, 2005;75:567–79.
  92. harrison Bs, Atala A, carbon nanotube applications for tissue engineering, Biomaterials, 2007;28:344–53.
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