Evaluation of a ß-Calcium Metaphosphate Bone Graft Containing Bone Morphogenetic Protein-7 in Rabbit Maxillary Defects

• Localización: Journal of periodontology, ISSN 0022-3492, Nº. 2, 2014, págs. 298-307
• Idioma: inglés
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• Resumen

  • Background: Calcium phosphate�based materials have been widely used as bone substitutes and more recently are being exploited together with growth factors as bone tissue engineering scaffolds regulating cell behavior. The aim of this study is to evaluate the in vitro and in vivo response to a newly developed calcium metaphosphate (CMP) bone graft, with and without bone-stimulating growth factor.

    Methods: Porous scaffolds of CMP were developed and extensively tested in vitro. Subsequently, CMP grafts with osteogenic protein-1 (OP-1) (test) and without OP-1 (control) were implanted into experimental rabbit maxillary bone defects. Animals were sacrificed at 2, 4, and 8 weeks, and samples were examined with microcomputed tomography (micro-CT) and processed for histomorphometric analysis.

    Results: At 8 weeks, the scaffolds containing OP-1 induced greater bone formation (P = 0.018) than CMP alone, based on histomorphometric evaluation (percentage bone area: test: 57.1 ± 5.6; control: 49.4 ± 7.7) and micro-CT analysis (percentage bone volume density: test: 63.46 ± 5.61; control: 51.20 ± 6.71). Thus, these data indicated that both test and control CMP grafts showed a good degree of bone formation. Furthermore, the CMP materials showed signs of resorption from 4 weeks, and no graft materials were observed at 8 weeks.

    Conclusions: In vitro, the OP-1 loaded graft demonstrated a release profile and bioactivity over a 28-day period. In vivo testing confirmed enhanced bone formation of the OP-1 loaded graft after 8 weeks of healing.

    Many techniques have been introduced to gain volume and quality of bone to accommodate implant placement. Bone substitutes are commonly used on their own or in combination with autogenous bone.1 Autografts are considered to be the �gold standard� for bone restoration because they contain living osteoprogenitor cells and provide osteoconductive surfaces that support cell migration and differentiation.2 However, autogenous bone grafts require a secondary intervention with associated morbidity at the harvest site.3 Furthermore, there are limitations as to the amount of bone that can be harvested for autogenous grafting. Hence, bone allografts, such as demineralized bone matrices, are frequently used, as well as a wide range of other natural4 and synthetic materials.5 In general, osteoinductive properties may need to be imparted by the incorporation of growth-stimulating factors. Numerous studies have been reported comparing the effectiveness of these as potential alternatives to autogenous bone grafts.6-9 Given the limitations of autogenous, allogenic, and synthetic materials, a paradigm shift is taking place in craniofacial and orthopedic medicine, with tissue engineering approaches using porous scaffolds in combination with growth factors, stem cells, or both.10 Ideally, a bioengineered bone graft should possess properties similar to natural bone and have clinically relevant dimensions to facilitate the remodeling and regeneration of the native tissue. Furthermore, induction of functional vessels and mineralization requires synchronization of cellular events, and these are controlled by spatial distribution of biologic cueing molecules at the appropriate physiologic dose and time. Several in vitro and in vivo studies show that bone morphogenetic proteins (BMPs) promote stem cell recruitment, proliferation, and differentiation and form endochondral bone in ectopic and heterotopic locations.11-13 BMP-2 and BMP-7 (osteogenic protein-1 [OP-1]) are generally accepted to be the most osteoinductive factors14 and are currently used clinically to induce new bone formation in spinal fusions§15 and long bone non-union fractures in combination with a suitable matrix, usually containing collagen.?16 Different materials have been evaluated as bone substitutes and scaffolds; among these, calcium phosphate (CaP) ceramics are considered among the most promising materials for bone tissue engineering because of their bone-like mineral composition and mechanical properties.17 The bioactivity of CaP ceramics has been linked to their ability to nucleate carbonate apatite crystals that are similar to bone mineral.18 The biodegradation properties of these materials allow for efficient bone tissue engineering because they can promote apatite formation and simultaneously deliver growth factors for osteoinduction.19 Although several studies have investigated the combination of osteoinductive factors with CaP ceramics, for example, hydroxyapatite (HA)20 or tricalcium phosphate (TCP),21 to the best of authors� knowledge, this is the first study that reports porous calcium metaphosphate (CMP) incorporating OP-1. Although CMP is slightly different in chemical structure to HA Ca10(PO4)6(OH)2 and TCP [Ca5(PO4)3], the composition of CMP [Ca(PO3)2] retains a close resemblance to the CaP component of bone. CMP is known to provoke specific responses at the interface of the materials, resulting in the formation of a strong bond between the tissue and material.22 The main purpose of this study is to evaluate and compare the in vivo osteoinductive activity of bioengineered CMP graft and CMP graft incorporating OP-1 when placed in a rabbit maxilla model.