Morphological and mechanical characterization of chitosan-calcium phosphate composites for potential application as bone-graft substitutes
Graaf, Guilherme Maia Mulder van de; Zoppa, Andre Luis do Valle De; Moreira, Rodrigo Crispim; Maestrelli, Sylma Carvalho; Marques, Rodrigo Fernando Costa; Campos, Maria Gabriela Nogueira
http://dx.doi.org/10.1590/2446-4740.0786
Res. Biomed. Eng., vol.31, n4, p.334-342, 2015
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Views: 909
Abstract
Introduction: Bone diseases, aging and traumas can cause bone loss and lead to bone defects. Treatment of bone defects is challenging, requiring chirurgical procedures. Bone grafts are widely used for bone replacement, but they are limited and expensive. Due to bone graft limitations, natural, semi-synthetic, synthetic and composite materials have been studied as potential bone-graft substitutes. Desirable characteristics of bone-graft substitutes are high osteoinductive and angiogenic potentials, biological safety, biodegradability, bone-like mechanical properties, and reasonable cost. Herein, we prepared and characterized potential bone-graft substitutes composed of calcium phosphate (CP) - a component of natural bone, and chitosan (CS) - a biocompatible biopolymer. Methods: CP-CS composites were synthetized, molded, dried and characterized. The effect of drying temperatures (38 and 60 °C) on the morphology, porosity and chemical composition of the composites was evaluated. As well, the effects of drying temperature and period of drying (3, 24, 48 and 72 hours) on the mechanical properties - compressive strength, modulus of elasticity and relative deformation-of the demolded samples were investigated. Results: Scanning electron microscopy and gas adsorption-desorption analyses of the CS-CP composites showed interconnected pores, indicating that the drying temperature played an important role on pores size and distribution. In addition, drying temperature have altered the color (brownish at 60 °C due to Maillard reaction) and the chemical composition of the samples, confirmed by FTIR. Conclusion: Particularly, prolonged period of drying have improved mechanical properties of the CS-CP composites dried at 38 °C, which can be designed according to the mechanical needs of the replaceable bone.
Keywords
Chitosan, Calcium phosphate, Bone-grafts, Substitutes, Mechanical properties.
References
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Bonher M, Galea L, Doebelin N. Calcium phosphate bone graft substitutes: failures and hopes. Journal of the European Ceramic Society. 2012; 32(11):2663-71.
Bonjour JP. Calcium and phosphate: a duet of ions playing for bone health. Journal of the American College of Nutrition. 2011; 30(Suppl 5):438S-48S. http://dx.doi.org/10.1080/07315724.2011.10719988. PMid:22081690.
Boskley AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. BoneKEy Reports. 2013; 2:1-9.
Calori GM, Mazza E, Colombo M, Ripamonti C. The use of bone-graft substitutes in large bone defects: any specific needs? Injury. 2011; 42(Suppl 2):56-63. http://dx.doi.org/10.1016/j.injury.2011.06.011. PMid:21752369.
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Jebahi S, Oudadesse H, Faouzi FZ, Elleuch J, Rebai T, Keskes H, Mostafa A, El Feki A. Osteoinduction and antiosteoporotic performance of hybrid biomaterial chitosan-bioactive glass graft: effects on bone remodeling. Journal of Material Science & Engineering. 2013; 3(2):1-8.
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Khan Y, Yaszemski MJ, Mikos AG, Laurencin CT. Tissue engineering of bone: material and matrix considerations. Journal of Bone and Joint Surgery. 2008; 90(Suppl 1):36-42. http://dx.doi.org/10.2106/JBJS.G.01260. PMid:18292355.
Kim S, Bedigrew K, Guda T, Maloney WJ, Park S, Wenke J, Yang YP. Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects. Acta Biomaterialia. 2014; 10(12):5021-33. http://dx.doi.org/10.1016/j.actbio.2014.08.028. PMid:25174669.
Kosaraju SL, Weerakkody R, Augustin MA. Chitosan-glucose conjugates: influence of extent of Maillard reaction on antioxidant properties. Journal of Agricultural and Food Chemistry. 2010; 58(23):12449-55. http://dx.doi.org/10.1021/jf103484z. PMid:21067178.
Kuboki Y, Takita H, Kobayashi D, Tsuruga E, Inoue E, Murata M, Nagai N, Dohi Y, Ohgushi H. BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: topology of osteogenesis. Journal of Biomedical Materials Research. 1998; 39(2):190-9. http://dx.doi.org/10.1002/(SICI)1097-4636(199802)39:2<190::AID-JBM4>3.0.CO;2-K. PMid:9457547.
Kung S, Devlin H, Fu E, Ho K-Y, Liang S-Y, Hsieh Y-D. The osteoinductive effect of chitosan-collagen composites around pure titanium implant surfaces in rats. Journal of Periodontal Research. 2011; 46(1):126-33. http://dx.doi.org/10.1111/j.1600-0765.2010.01322.x. PMid:21108645.
Li J, Baker BA, Mou X, Ren N, Qiu J, Boughton RI, Liu H. Biopolymer/calcium phosphate scaffolds for bone tissue engineering. Advanced Healthcare Materials. 2014; 3(4):469-84. http://dx.doi.org/10.1002/adhm.201300562. PMid:24339420.
Liu H, Li H, Cheng W, Yang Y, Zhu M, Zhou C. Novel injectable calcium phosphate/chitosan composites for bone substitute materials. Acta Biomaterialia. 2006; 2(5):557-65. http://dx.doi.org/10.1016/j.actbio.2006.03.007. PMid:16774852.
Madihally SV, Matthew HWT. Porous chitosan scaffolds for tissue engineering. Biomaterials. 1999; 20(12):1133-42. http://dx.doi.org/10.1016/S0142-9612(99)00011-3. PMid:10382829.
Martino AD, Sittinger M, Risbud MV. Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials. 2005; 26(30):5983-90. http://dx.doi.org/10.1016/j.biomaterials.2005.03.016. PMid:15894370.
Moshiri A, Oryan A. Role of tissue engineering in tendon reconstructive surgery and regenerative medicine: current concepts, approaches and concerns. Hard Tissue. 2012; 1(2):1-11. http://dx.doi.org/10.13172/2050-2303-1-2-291.
New N, Furuike T, Tamura H. The mechanical and biological properties of chitosan scaffolds for tissue regeneration templates are significantly enhanced by chitosan from gongronella butleri. Materials (Basel). 2009; (2):374-98.
Oryan A, Alidadi S, Moshiri A. Current concerns regarding healing of bone defects. Hard Tissue. 2013; 26(2):1-12.
Penk A, Förster Y, Scheidt HA, Nimptsch A, Hacker MC, Schulz-Siegmund M, Ahnert P, Schiller J, Rammelt S, Huster D. The pore size of PLGA bone implants determines the de novo formation of bone tissue in tibial head defects in rats. Magnetic Resonance in Medicine. 2013; 70(4):925-35. http://dx.doi.org/10.1002/mrm.24541. PMid:23165861.
Perren, SM. Evolution of the internal fixation of long bone fractures: the scientific basis of biological internal fixation: choosing a new balance between stability and biology. The Bone & Joint Journal. 2002; 84(B):1093-110.
Pillai CKS, Paul W, Sharma CP. Chitin and chitosan polymers: chemistry, solubility and fiber formation. Progress in Polymer Science. 2009; 34(7):641-78. http://dx.doi.org/10.1016/j.progpolymsci.2009.04.001.
Rinaudo M. Chitin and chitosan: properties and applications. Progress in Polymer Science. 2006; 31(7):603-32. http://dx.doi.org/10.1016/j.progpolymsci.2006.06.001.
Romani WA, Gieck JH, Perrin DH, Saliba EN, Kahler DM. Mechanisms and management of stress fractures in physically active persons. Journal of Athletic Training. 2002; 37(3):306-14. PMid:16558676.
Scaglione S, Giannoni P, Bianchini P, Sandri M, Marotta R, Firpo G, Valbusa U, Tampieri A, Diaspro A, Bianco P, Quarto R. Order versus disorder: in vivo bone formation within osteoconductive scaffolds. Scientific Reports. 2012; 2(274):1-6. PMid:22355786.
Smulders E, van Lankveld W, Laan R, Duysens J, Weerdesteyn V. Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopedic surgery. BMC Musculoskeletal Disorders. 2011; 12(34):1-14. PMid:21199576.
Spin-Neto R, Pavone C, Freitas RM, Marcantonio RAC, Marcantonio-Júnior E. Biomateriais à base de quitosana com aplicação médica e odontológica: revisão de literatura. Revista de Odontologia da UNESP. 2008; 37(2):155-61.
Sumner-Smith G. Bone in clinical orthopedics. 2nd ed. Dübendorf: AO Publishing; 2002.
Umemura K, Kawai S. Modification of chitosan by the Maillard reaction using cellulose model compounds. Carbohydrate Polymers. 2007; 68(2):242-8. http://dx.doi.org/10.1016/j.carbpol.2006.12.014.
Venkatesan J, Vinodhini PA, Sudha PN, Kim S-K. Chitin and chitosan composites for bone tissue regeneration. Advances in Food and Nutrition Research. 2014; 73:59-81. http://dx.doi.org/10.1016/B978-0-12-800268-1.00005-6. PMid:25300543.
Wennerberg A, Ektessabi A, Albrektsson T, Johansson C, Andersson B. A 1-year follow-up of implants of differing surface roughness placed in rabbit bone. The International Journal of Oral & Maxillofacial Implants. 1997; 12(4):486-94. PMid:9274077.
Yamada S, Heymann D, Bouler J-M, Daculsi G. Osteoclastic resorption of calcium phosphate ceramics with different hydroxyapatite/β-tricalcium phosphate ratios. Biomaterials. 1997; 18(15):1037-41. http://dx.doi.org/10.1016/S0142-9612(97)00036-7. PMid:9239465.
Zhang Y, Zhang M. Three-dimensional macroporous calcium phosphate bioceramics with nested chitosan sponges for load-bearing bone implants. Journal of Biomedical Materials Research. Part A. 2002; 61(1):1-8. http://dx.doi.org/10.1002/jbm.10176. PMid:12001239.
Armentano I, Dottori M, Fortunati E, Mattioli S, Kenny JM. Biodegradable polymer matrix nanocomposites for tissue engineering: a review. Polymer Degradation & Stability. 2010; 95(11):2126-46. http://dx.doi.org/10.1016/j.polymdegradstab.2010.06.007.
Associação Brasileira de Normas Técnicas. NBR ISO 5833: implantes para cirurgia - cimentos de resina acrílica. Rio de Janeiro: ABNT; 2004.
Bongio M, van den Beucken JJJP, Leeuwenburgh SCG, Jansen JA. Development of bone substitute materials: from ‘biocompatible’ to ‘instructive’. Journal of Materials Chemistry. 2010; 20(40):8747-59. http://dx.doi.org/10.1039/c0jm00795a.
Bonher M, Galea L, Doebelin N. Calcium phosphate bone graft substitutes: failures and hopes. Journal of the European Ceramic Society. 2012; 32(11):2663-71.
Bonjour JP. Calcium and phosphate: a duet of ions playing for bone health. Journal of the American College of Nutrition. 2011; 30(Suppl 5):438S-48S. http://dx.doi.org/10.1080/07315724.2011.10719988. PMid:22081690.
Boskley AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. BoneKEy Reports. 2013; 2:1-9.
Calori GM, Mazza E, Colombo M, Ripamonti C. The use of bone-graft substitutes in large bone defects: any specific needs? Injury. 2011; 42(Suppl 2):56-63. http://dx.doi.org/10.1016/j.injury.2011.06.011. PMid:21752369.
Chung Y-C, Luo C-L, Chen C-C. Preparation and important functional properties of water-soluble chitosan produced through Maillard reaction. Bioresource Technology. 2005; 96(13):1473-82. http://dx.doi.org/10.1016/j.biortech.2004.12.001. PMid:15939275.
Dabrowski B, Swieszkowski W, Godlinski D, Kurzydlowski KJ. Highly porous titanium scaffolds for orthopaedic applications. Journal of Biomedical Materials Research. Part B, Applied Biomaterials. 2010; 95(1):53-61. http://dx.doi.org/10.1002/jbm.b.31682. PMid:20690174.
Deligianni DD, Katsala ND, Koutsoukos PG, Missirlis YF. Effect of surface roughness of hydroxyapatite on human bone marrow cell adhesion, proliferation, differentiation and detachment strength. Biomaterials. 2001; 22(1):87-96. http://dx.doi.org/10.1016/S0142-9612(00)00174-5. PMid:11085388.
Hing KA, Wilson LF, Buckland T. Comparative performance of three ceramic bone graft substitutes. The Spine Journal. 2007; 7(4):475-90. http://dx.doi.org/10.1016/j.spinee.2006.07.017. PMid:17630146.
Hu MH, Lee PY, Chen WC, Hu JJ. Comparison of three calcium phosphate bone graft substitutes from biomechanical, histological, and crystallographic perspectives using a rat posterolateral lumbar fusion model. Materials Science and Engineering C. 2014; 45:82-8. http://dx.doi.org/10.1016/j.msec.2014.08.065. PMid:25491804.
Hutmacher DW. Scaffolds in tissue engineering bone and cartilage. Biomaterials. 2000; 21(24):2529-43. http://dx.doi.org/10.1016/S0142-9612(00)00121-6. PMid:11071603.
Jebahi S, Oudadesse H, Faouzi FZ, Elleuch J, Rebai T, Keskes H, Mostafa A, El Feki A. Osteoinduction and antiosteoporotic performance of hybrid biomaterial chitosan-bioactive glass graft: effects on bone remodeling. Journal of Material Science & Engineering. 2013; 3(2):1-8.
Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials. 2005; 26(27):5474-91. http://dx.doi.org/10.1016/j.biomaterials.2005.02.002. PMid:15860204.
Khan Y, Yaszemski MJ, Mikos AG, Laurencin CT. Tissue engineering of bone: material and matrix considerations. Journal of Bone and Joint Surgery. 2008; 90(Suppl 1):36-42. http://dx.doi.org/10.2106/JBJS.G.01260. PMid:18292355.
Kim S, Bedigrew K, Guda T, Maloney WJ, Park S, Wenke J, Yang YP. Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects. Acta Biomaterialia. 2014; 10(12):5021-33. http://dx.doi.org/10.1016/j.actbio.2014.08.028. PMid:25174669.
Kosaraju SL, Weerakkody R, Augustin MA. Chitosan-glucose conjugates: influence of extent of Maillard reaction on antioxidant properties. Journal of Agricultural and Food Chemistry. 2010; 58(23):12449-55. http://dx.doi.org/10.1021/jf103484z. PMid:21067178.
Kuboki Y, Takita H, Kobayashi D, Tsuruga E, Inoue E, Murata M, Nagai N, Dohi Y, Ohgushi H. BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: topology of osteogenesis. Journal of Biomedical Materials Research. 1998; 39(2):190-9. http://dx.doi.org/10.1002/(SICI)1097-4636(199802)39:2<190::AID-JBM4>3.0.CO;2-K. PMid:9457547.
Kung S, Devlin H, Fu E, Ho K-Y, Liang S-Y, Hsieh Y-D. The osteoinductive effect of chitosan-collagen composites around pure titanium implant surfaces in rats. Journal of Periodontal Research. 2011; 46(1):126-33. http://dx.doi.org/10.1111/j.1600-0765.2010.01322.x. PMid:21108645.
Li J, Baker BA, Mou X, Ren N, Qiu J, Boughton RI, Liu H. Biopolymer/calcium phosphate scaffolds for bone tissue engineering. Advanced Healthcare Materials. 2014; 3(4):469-84. http://dx.doi.org/10.1002/adhm.201300562. PMid:24339420.
Liu H, Li H, Cheng W, Yang Y, Zhu M, Zhou C. Novel injectable calcium phosphate/chitosan composites for bone substitute materials. Acta Biomaterialia. 2006; 2(5):557-65. http://dx.doi.org/10.1016/j.actbio.2006.03.007. PMid:16774852.
Madihally SV, Matthew HWT. Porous chitosan scaffolds for tissue engineering. Biomaterials. 1999; 20(12):1133-42. http://dx.doi.org/10.1016/S0142-9612(99)00011-3. PMid:10382829.
Martino AD, Sittinger M, Risbud MV. Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials. 2005; 26(30):5983-90. http://dx.doi.org/10.1016/j.biomaterials.2005.03.016. PMid:15894370.
Moshiri A, Oryan A. Role of tissue engineering in tendon reconstructive surgery and regenerative medicine: current concepts, approaches and concerns. Hard Tissue. 2012; 1(2):1-11. http://dx.doi.org/10.13172/2050-2303-1-2-291.
New N, Furuike T, Tamura H. The mechanical and biological properties of chitosan scaffolds for tissue regeneration templates are significantly enhanced by chitosan from gongronella butleri. Materials (Basel). 2009; (2):374-98.
Oryan A, Alidadi S, Moshiri A. Current concerns regarding healing of bone defects. Hard Tissue. 2013; 26(2):1-12.
Penk A, Förster Y, Scheidt HA, Nimptsch A, Hacker MC, Schulz-Siegmund M, Ahnert P, Schiller J, Rammelt S, Huster D. The pore size of PLGA bone implants determines the de novo formation of bone tissue in tibial head defects in rats. Magnetic Resonance in Medicine. 2013; 70(4):925-35. http://dx.doi.org/10.1002/mrm.24541. PMid:23165861.
Perren, SM. Evolution of the internal fixation of long bone fractures: the scientific basis of biological internal fixation: choosing a new balance between stability and biology. The Bone & Joint Journal. 2002; 84(B):1093-110.
Pillai CKS, Paul W, Sharma CP. Chitin and chitosan polymers: chemistry, solubility and fiber formation. Progress in Polymer Science. 2009; 34(7):641-78. http://dx.doi.org/10.1016/j.progpolymsci.2009.04.001.
Rinaudo M. Chitin and chitosan: properties and applications. Progress in Polymer Science. 2006; 31(7):603-32. http://dx.doi.org/10.1016/j.progpolymsci.2006.06.001.
Romani WA, Gieck JH, Perrin DH, Saliba EN, Kahler DM. Mechanisms and management of stress fractures in physically active persons. Journal of Athletic Training. 2002; 37(3):306-14. PMid:16558676.
Scaglione S, Giannoni P, Bianchini P, Sandri M, Marotta R, Firpo G, Valbusa U, Tampieri A, Diaspro A, Bianco P, Quarto R. Order versus disorder: in vivo bone formation within osteoconductive scaffolds. Scientific Reports. 2012; 2(274):1-6. PMid:22355786.
Smulders E, van Lankveld W, Laan R, Duysens J, Weerdesteyn V. Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopedic surgery. BMC Musculoskeletal Disorders. 2011; 12(34):1-14. PMid:21199576.
Spin-Neto R, Pavone C, Freitas RM, Marcantonio RAC, Marcantonio-Júnior E. Biomateriais à base de quitosana com aplicação médica e odontológica: revisão de literatura. Revista de Odontologia da UNESP. 2008; 37(2):155-61.
Sumner-Smith G. Bone in clinical orthopedics. 2nd ed. Dübendorf: AO Publishing; 2002.
Umemura K, Kawai S. Modification of chitosan by the Maillard reaction using cellulose model compounds. Carbohydrate Polymers. 2007; 68(2):242-8. http://dx.doi.org/10.1016/j.carbpol.2006.12.014.
Venkatesan J, Vinodhini PA, Sudha PN, Kim S-K. Chitin and chitosan composites for bone tissue regeneration. Advances in Food and Nutrition Research. 2014; 73:59-81. http://dx.doi.org/10.1016/B978-0-12-800268-1.00005-6. PMid:25300543.
Wennerberg A, Ektessabi A, Albrektsson T, Johansson C, Andersson B. A 1-year follow-up of implants of differing surface roughness placed in rabbit bone. The International Journal of Oral & Maxillofacial Implants. 1997; 12(4):486-94. PMid:9274077.
Yamada S, Heymann D, Bouler J-M, Daculsi G. Osteoclastic resorption of calcium phosphate ceramics with different hydroxyapatite/β-tricalcium phosphate ratios. Biomaterials. 1997; 18(15):1037-41. http://dx.doi.org/10.1016/S0142-9612(97)00036-7. PMid:9239465.
Zhang Y, Zhang M. Three-dimensional macroporous calcium phosphate bioceramics with nested chitosan sponges for load-bearing bone implants. Journal of Biomedical Materials Research. Part A. 2002; 61(1):1-8. http://dx.doi.org/10.1002/jbm.10176. PMid:12001239.
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