Abstract
Despite several efforts to find suitable alternatives to autologous bone, no bone substitute currently available provides the same characteristics and properties. Nevertheless, among the wide range of materials proposed as bone substitutes, calcium phosphate materials represent the most promising category and the present study is aimed at improving the knowledge on non-stoichiometric magnesium-doped hydroxyapatite substitutes (Mg-HA), tested in two different formulations: Mg-HA Putty and Mg-HA Granules. These bone substitutes were implanted bilaterally into iliac crest bone defects in healthy sheep and comparative histological, histomorphometric, microhardness and ultrastructural assessments were performed 9, 12, 18 and 24 months after surgery to elucidate bone tissue apposition, mineralization and material degradation in vivo. The results confirmed that the biomimetic bone substitutes provide a histocompatible and osteoconductive structural support, during the bone formation process, and give essential information about the in vivo resorption process and biological behavior of biomimetic bone substitutes.
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Greenwald AS, Boden S, Goldberg VM, Khan Y, Laurencin CT, Rosier RN. Bone-graft substitutes: facts, fictions, and applications. J Bone Joint Surg Am. 2001;83-A(Suppl 2 Pt 2):98–103.
US Bone Grafts Industry. Global Industry Analysts Inc; 2011. http://www.reportlinker.com/p0119465-summary/World-Bone-Grafts-Market.html.
Ahlmann E, Patzakis M, Roidis N, Shepherd L, Holtom P. Comparison of anterior and posterior iliac crest bone grafts in terms of harvest-site morbidity and functional outcomes. J Bone Joint Surg Am. 2002;84-A:716–20.
Zimmermann G, Moghaddam A. Allograft bone matrix versus synthetic bone graft substitutes. Injury. 2011;42:S16–21.
Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury. 2005;36S:S20–7.
De Long W, Einhorn TA, Koval K, McKee M, Smith W, Sanders R, Watson T. Bone grafts and bone graft substitutes in orthopaedic trauma surgery. A critical analysis. J Bone Joint Surg Am. 2007;89:649–58.
Cornell CN. Osteobiologics. Bull Hosp Jt Dis. 2004;62:13–7.
Oliveira AL, Mano JF, Reis RL. Nature-inspired calcium phosphate coatings: present status and novel advances in the science of mimicry. Curr Opin Sol St M. 2003;7:309–18.
Tampieri A, Sprio S, Sandri M, Valentini F. Mimicking natural bio-mineralization processes: a new tool for osteochondral scaffold development. Trends Biotechnol. 2011;29:526–35.
Panzavolta S, Torricelli P, Bracci B, Fini M, Bigi A. Functionalization of biomimetic calcium phosphate bone cements with alendronate. J Inorg Biochem. 2010;104:1099–106.
Palmer LC, Newcomb CJ, Kaltz SR, Spoerke ED, Stupp SI. Biomimetic systems for hydroxyapatite mineralization inspired by bone and enamel. Chem Rev. 2008;108:4754–83.
Larsson S. Calcium phosphates: what is the evidence? J Orthop Trauma. 2010;24:S41–5.
Martini L, Staffa G, Giavaresi G, Salamanna F, Parrilli A, Serchi E, Pressato D, Arcangeli E, Fini M. Long-term results following a cranial hydroxyapatite prosthesis implantation in a large skull defect model. Plast Reconstr Surg. 2012;129:625e–35e.
Verron E, Khairoun I, Guicheux J, Bouler JM. Calcium phosphate biomaterials as bone drug delivery systems: a review. Drug Discov Today. 2010;15:547–52.
Landi E, Logroscino G, Proietti L, Tampieri A, Sandri M, Sprio S. Biomimetic Mg-substitute hydroxyapatite: from synthesis o in vivo behaviour. J Mater Sci Mater Med. 2008;19:239–47.
Ren F, Leng Y, Xin R, Ge X. Synthesis, characterization and ab initio simulation of magnesium-substituted hydroxyapatite. Acta Biomater. 2010;6:2787–96.
Yamasakia Y, Yoshidab Y, Okazaki M, Shimazuc A. Action of FGMgCO3Ap-collagen composite in promoting bone formation. Biomaterials. 2003;24:4913–20.
Caneva M, Botticelli D, Stellini E, Sousa SL, Salata LA, Lang NP. Magnesium-enriched hydroxyapatite at immediate implants: a histomorphometric study in dogs. Clin Oral Impl Res. 2011;22:512–7.
Crespi R, Capparè P, Gherlone E. Magnesium- enriched hydroxyapatite compared to calcium sulfate in the healing of human extraction sockets: radiographic and histomorphometric evaluation at 3 months. J Periodontol. 2009;80:210–8.
Crespi R, Capparè P, Gherlone E. Dental implants placed in extraction sites grafted with different bone substitutes: radiographic evaluation at 24 months. J Periodontol. 2009;80:1616–21.
Checchi V, Savarino L, Montevecchi M, Felice P, Checchi L. Clinical-radiographic and histological evaluation of two hydroxyapatites in human extraction sockets: a pilot study. Int J Oral Maxillofac Surg. 2011;40:526–32.
Landi E, Tampieri A, Mattioli-Belmonte M, Celotti G, Sandri M, Gigante A, Fava P, Biagini G. Biomimetic Mg- and MgCO3-substituted hydroxyapatites: synthesis characterization and in vitro behaviour. J Eur Ceram Soc. 2006;26:2593–601.
Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res. 1987;2:595–610.
Bohner M, Galea L, Doebelin N. Calcium phosphate bone graft substitutes: failure and hopes. J Europ Cer Soc. 2012;32:2663–71.
Oonishi H, Hench LL, Wilson J, Sugihara F, Tsuji E, Kushitani S, Iwaki H. Comparative bone growth behavior in granules of bioceramic materials of various sizes. J Biomed Mater Res. 1999;44:31–43.
Tampieri A, Celotti G, Landi E. From biomimetic apatites to biologically inspired composites. Anal Bioanal Chem. 2005;381:568–76.
Bertinetti L, Tampieri A, Landi E, Martra G, Coluccia S. Punctual investigation of surface sites of HA and magnesium-HA. J Europ Cer Soc. 2006;26:987–91.
LeGeros RZ. Calcium phosphate-based osteoinductive materials. Chem Rev. 2008;108:4742–53.
Figueiredo M, Henriques J, Martins G, Guerra F, Judas F, Figueiredo H. Physicochemical characterization of biomaterials commonly used in dentistry as bone substitutes-comparison with human bone. J Biomed Mater Res Part B Appl Biomater. 2010;92B:409–19.
Matè-Sanchez de Val JE, Calvo Guirado JL, Delgado-Ruiz RA, Ramírez-Fernández MP, Negri B, Abboud M, Martínez IM, de Aza PN. Physical properties, mechanical behavior, and electron microscopy study of a new α-TCP block graft with silicon in an animal model. J Biomed Mater Res A. 2012;100:3446–54.
Ramírez-Fernández MP, Calvo-Guirado JL, Maté-Sánchez Del Val JE, Delgado-Ruiz RA, Negri B, Barona-Dorado C. Ultrastructural study by backscattered electron imaging and elemental microanalysis of bone-to-biomaterial interface and mineral degradation of porcine xenografts used in maxillary sinus floor elevation. Clin Oral Implants Res. 2013;24:523–30.
Ramírez-Fernández MP, Calvo-Guirado JL, Delgado-Ruiz RA, Maté-Sánchez del Val JE, Negri B, Diago MP. Ultrastructural study by backscattered electron imaging and elemental microanalysis of biomaterial-to-bone interface and mineral degradation of bovine xenografts in maxillary sinus floor elevation. Clin Oral Implants Res. 2013;24:645–51.
Schouten C, Meijer GJ, van den Beucken JJ, Spauwen PH, Jansen JA. A novel implantation model for evaluation of bone healing response to dental implants: the goat iliac crest. Clin Oral Implants Res. 2010;21:414–23.
Biemond JE, Eufrásio TS, Hannink G, Verdonschot N, Buma P. Assessment of bone ingrowth potential of biomimetic hydroxyapatite and brushite coated porous E-beam structures. J Mater Sci Mater Med. 2011;22:917–25.
Gogolewski S, Gorna K. Biodegradable polyurethane cancellous bone graft substitutes in the treatment of iliac crest defects. J Biomed Mater Res. 2007;80A:94–101.
Acknowledgments
The authors are grateful to Dr. M. C. Maltarello for his excellent assistance in EDS investigation and also to Mr. Keith Smith for his assistance in language supervision. This paper was partially supported by Rizzoli Orthopaedic Institute, “5 PER MILLE Project-Year 2010”.
Conflict of interest
This study was supported by a grant from Fin-Ceramica Faenza S.p.A., Faenza (RA), Italy (for providing biomaterial, costs of animals, animal housing and analyses). Dolcini L. and Pressato D. are employees of this company and declare the existence of a potential conflict of interest. The other authors declare no conflict of interest with the materials used in the present evaluation.
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Sartori, M., Giavaresi, G., Tschon, M. et al. Long-term in vivo experimental investigations on magnesium doped hydroxyapatite bone substitutes. J Mater Sci: Mater Med 25, 1495–1504 (2014). https://doi.org/10.1007/s10856-014-5177-5
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DOI: https://doi.org/10.1007/s10856-014-5177-5