The advantages of synthetic bone graft substitutes over autogenous bone grafts include abundant graft volume, lack of complications related to the graft harvesting, and shorter operation and recovery times for the patient. We studied a new synthetic supercritical CO2 –processed porous composite scaffold of β-tricalcium phosphate and poly(L-lactide-co-caprolactone) copolymer as a bone graft substitute in a rabbit calvarial defect. Bilateral 12 mm diameter critical size calvarial defects were successfully created in 18 rabbits. The right defect was filled with a scaffold moistened with bone marrow aspirate, and the other was an empty control. The material was assessed for applicability during surgery. The follow-up times were 4, 12, and 24 weeks. Radiographic and micro-CT studies and histopathological analysis were used to evaluate new bone formation, tissue ingrowth, and biocompatibility. The scaffold was easy to shape and handle during the surgery, and the bone-scaffold contact was tight when visually evaluated after the implantation. The material showed good biocompatibility and its porosity enabled rapid invasion of vasculature and full thickness mesenchymal tissue ingrowth already at four weeks. By 24 weeks, full thickness bone ingrowth within the scaffold and along the dura was generally seen. In contrast, the empty defect had only a thin layer of new bone at 24 weeks. The radiodensity of the material was similar to the density of the intact bone. In conclusion, the new porous scaffold material, composed of microgranular β-TCP bound into the polymer matrix, proved to be a promising osteoconductive bone graft substitute with excellent handling properties.
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Calori GM, Mazza E, Colombo M, Ripamonti C. The use of bone-graft substitutes in large bone defects: any specific needs? Injury. 2011;42:56–63.
Moore WR, Graves SE, Bain GI. Synthetic bone graft substitutes. Anz J Surg. 2001;71:354–61.
Myeroff C, Archdeacon M. Autogenous bone graft: donor sites and techniques. J Bone Jt Surg. 2011;93:2227–36.
Fillingham Y, Jacobs J. Bone grafts and their substitutes. Bone Join J. 2016;98(1 Suppl A):6–9.
Schnee CL, Freese A, Weil RJ, Marcotte PJ. Analysis of harvest morbidity and radiographic outcome using autograft for anterior cervical fusion. Spine. 1997;22:2222–7.
Sawin PD, Traynelis VC, Menezes AH. A comparative analysis of fusion rates and donor-site morbidity for autogeneic rib and iliac crest bone grafts in posterior cervical fusions. J Neurosurg. 1998;88:255–65.
Ebraheim NA, Elgafy H, Xu R. Bone-graft harvesting from iliac and fibular donor sites: techniques and complications. J Am Acad Orthop Surg. 2001;9:210–8.
Dimitriou R, Mataliotakis GI, Angoules AG, Kanakaris NK, Giannoudis PV. Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review. Injury. 2011;42:3–15.
Bizenjima T, Takeuchi T, Seshima F, Saito A. Effect of poly(lactide‐co‐glycolide) (PLGA)‐coated beta‐tricalcium phosphate on the healing of rat calvarial bone defects: a comparative study with pure‐phase beta‐tricalcium phosphate. Clin Oral Implants Res. 2016;27:1360–7.
Hak DJ. The use of osteoconductive bone graft substitutes in orthopaedic trauma. J Am Acad Orthop Surg. 2007;15:525–36.
Thaler M, Lechner R, Gstöttner M, Kobel C, Bach C. The use of beta-tricalcium phosphate and bone marrow aspirate as a bone graft substitute in posterior lumbar interbody fusion. Eur Spine J. 2013;22:1173–82.
Albee FH. Studies in bone growth: triple calcium phosphate as a stimulus to osteogenesis. Ann Surg. 1920;71:32–9.
Zerbo IR, Zijderveld SA, de Boer A, Bronckers AL, de Lange G, ten Bruggenkate CM, et al. Histomorphometry of human sinus floor augmentation using a porous beta-tricalcium phosphate: a prospective study. Clin Oral Implants Res. 2004;15:724–32.
Zijderveld S, Zerbo I, van den Bergh J, Schulten E, ten Bruggenkate C. Maxillary sinus floor augmentation using a β-tricalcium phosphate (Cerasorb) alone compared to autogenous bone grafts. Int J Oral Maxillofac Implants. 2005;20:432–40.
Ghanaati S, Barbeck M, Orth C, Willershausen I, Thimm BW, Hoffmann C, et al. Influence of β-tricalcium phosphate granule size and morphology on tissue reaction in vivo. Acta Biomater. 2010;6:4476–87.
Zerbo IR, Bronckers AL, de Lange G, Burger EH. Localisation of osteogenic and osteoclastic cells in porous β-tricalcium phosphate particles used for human maxillary sinus floor elevation. Biomaterials . 2005;26:1445–51.
Honda M, Yada T, Ueda M, Kimata K. Cartilage formation by cultured chondrocytes in a new scaffold made of poly(L-lactide-ϵ-caprolactone) sponge. J Oral Maxillofac Surg. 2000;58:767–75.
Honda M, Morikawa N, Hata K, Yada T, Morita S, Ueda M, et al. Rat costochondral cell characteristics on poly (l-lactide-co- ε-caprolactone) scaffolds. Biomaterials . 2003;24:3511–9.
Jeong SI, Kim SH, Kim YH, Kim B, Kang SW, Kwon JH, et al. In vivo biocompatibilty and degradation behavior of elastic poly(l-lactide- co- ε-caprolactone) scaffolds. Biomaterials . 2004;25:5939–46.
Nandi SK, Roy S, Mukherjee P, Kundu B, De DK, Basu D. Orthopaedic applications of bone graft & graft substitutes: a review. Indian J Med Res. 2010;132:15–30.
Hernigou P, Desroches A, Queinnec S, Flouzat Lachaniette C, Poignard A, Allain J, et al. Morbidity of graft harvesting versus bone marrow aspiration in cell regenerative therapy. Int Orthop. 2014;38:1855–60.
Luvizuto ER, Queiroz TP, Margonar R, Panzarini SR, Hochuli-Vieira E, Okamoto T, et al. Osteoconductive properties of β-tricalcium phosphate matrix, polylactic and polyglycolic acid gel, and calcium phosphate cement in bone defects. J Craniofac Surg. 2012;23:e430–3.
Tanuma Y, Matsui K, Kawai T, Matsui A, Suzuki O, Kamakura S. et al.Comparison of bone regeneration between octacalcium phosphate/collagen composite and β-tricalcium phosphate in canine calvarial defect.Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;115:9–17.
Lappalainen O, Karhula S, Haapea M, Kyllönen L, Haimi S, Miettinen S, et al. Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds. Childs Nerv Syst. 2016;32:681–8.
Hernandes C. J. Cancellous bone. In: Murphy W, Black J, Hastings G, editors. Handbook of biomaterial properties. New York: Springer-Verlag; 2016. pp 15–21.
Tsuruga E, Takita H, Itoh H, Wakisaka Y, Kuboki Y. Pore size of porous hydroxyapatite as the cell-substratum controls BMP-induced osteogenesis. J Biochem. 1997;121:317–24.
Karageorgiou V, Kaplan D. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials . 2005;26:5474–91.
Gosain AK, Santoro TD, Song L, Capel CC, Sudhakar PV, Matloub HS. Osteogenesis in calvarial defects: contribution of the dura, the pericranium, and the surrounding bone in adult versus infant animals. Plast Reconstr Surg. 2003;112:515–27.
Lappalainen O, Karhula SS, Haapea M, Kauppinen S, Finnilä M, Saarakkala S, et al. Micro-CT analysis of bone healing in rabbit calvarial critical-sized defects with solid bioactive glass, tricalcium phosphate granules or autogenous bone. J Oral Macillofac Res. 2016;7:e4.
Jan A, Sándor G, Brkovic B, Peel S, Kim YD, Xiao W, et al. Effect of hyperbaric oxygen on demineralized bone matrix and biphasic calcium phosphate bone substitutes. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109:59–66.
Ghanaati S, Barbeck M, Willershausen I, Thimm B, Stuebinger S, Korzinskas T, et al. Nanocrystalline hydroxyapatite bone substitute leads to sufficient bone tissue formation already after 3 months: histological and histomorphometrical analysis 3 and 6 months following human sinus cavity augmentation. Clin Implant Dent Relat Res. 2013;15:883–92.
Miron RJ, Zohdi H, Fujioka-Kobayashi M, Bosshardt DD. Giant cells around bone biomaterials: osteoclasts or multi-nucleated giant cells? Acta Biomater. 2016;46:15–28.
Barbeck M, Booms P, Unger R, Hoffmann V, Sader R, Kirkpatrick CJ, et al. Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells—new insights into the material‐mediated healing process. J Biomed Mater Res A. 2017;105:1105–11.
Peltola M, Kinnunen I, Aitasalo K. Reconstruction of orbital wall defects with bioactive glass plates. J Oral Macillofac Surg. 2008;66:639–46.
van Haaren EH, Smit TH, Phipps K, Wuisman PI, Blunn G, Heyligers IC. Tricalcium-phosphate and hydroxyapatite bone-graft extender for use in impaction grafting revision surgery. J Bone Jt Surg Br. 2005;87:267–71.
Oakley J, Kuiper JH. Factors affecting the cohesion of impaction bone graft. J Bone Jt Surg [Br]. 2006;88:828–31.
Schroeder C, Grupp T, Fritz B, Schilling C, Chevalier Y, Utzschneider S, et al. The influence of third-body particles on wear rate in unicondylar knee arthroplasty: a wear simulator study with bone and cement debris. J Mater Sci Mater Med. 2013;24:1319–25.
Sanda M, Shiota M, Fujii M, Kon K, Fujimori T, Kasugai S. Capability of new bone formation with a mixture of hydroxyapatite and beta‐tricalcium phosphate granules. Clin Oral Implants Res. 2015;26:1369–74.
Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res. 1986;205:299–308.
Fok T, Jan A, Peel S, Evans AW, Clokie C, Sándor G. Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical-sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105:417–22.
Jan A, Sándor G, Iera D, Mhawi A, Peel S, Evans AW, et al. Hyperbaric oxygen results in an increase in rabbit calvarial critical sized defects. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:144–9.
Cooper GM, Mooney MP, Gosain AK, Campbell PG, Losee JE, Huard J. Testing the critical size in calvarial bone defects: revisiting the concept of a critical-size defect. Plast Reconstr Surg. 2010;125:1685–92.
Borie E, Fuentes R, del Sol M, Oporto G, Engelke W. The influence of FDBA and autogenous bone particles on regeneration of calvaria defects in the rabbit: a pilot study. Ann Anat. 2011;193:412–7.
Pelegrine AA, Aloise AC, Zimmermann A, Mello e Oliveira R, Ferreira LM. Repair of critical‐size bone defects using bone marrow stromal cells: a histomorphometric study in rabbit calvaria. Part I: Use of fresh bone marrow or bone marrow mononuclear fraction. Clin Oral Implants Res. 2014;25:567–72.
This study was financially supported by the Finnish Funding Agency for Technology and Innovation (40326/13) and by grants from the Finnish Foundation of Veterinary Research and The Finnish Veterinary Foundation. The authors kindly acknowledge DVM Mikael Morelius for the help with surgical procedures.
Conflict of interest
The authors declare that they have no conflict of interest.
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Pihlman, H., Keränen, P., Paakinaho, K. et al. Novel osteoconductive β-tricalcium phosphate/poly(L-lactide-co-e-caprolactone) scaffold for bone regeneration: a study in a rabbit calvarial defect. J Mater Sci: Mater Med 29, 156 (2018). https://doi.org/10.1007/s10856-018-6159-9