Bone Regeneration via a Mineral Substrate and Induced Angiogenesis

Abstract

Angiogenesis and biomineral substrates play major roles in bone development and regeneration. We hypothesized that macroporous scaffolds of biomineralized 85:15 poly(lactide-co-glycolide), which locally release vascular endothelial growth factor-165 (VEGF), would direct simultaneous regeneration of bone and vascular tissue. The presence of a bone-like biomineral substrate significantly increased regeneration of osteoid matrix (32 +/- 7% of total tissue area; mean +/- SD; p < 0.05) and mineralized tissue (14 +/- 2%; P < 0.05) within a rat cranium critical defect compared with a non-mineralized polymer scaffold (19 +/- 8% osteoid and 10 +/- 2% mineralized tissue). Further, the addition of VEGF to a mineralized substrate significantly increased the generation of mineralized tissue (19 +/- 4%; P < 0.05) compared with mineralized substrate alone. This appeared to be due to a significant increase in vascularization throughout VEGF-releasing scaffolds (52 +/- 9 vessels/mm(2); P < 0.05) compared with mineralized scaffolds without VEGF (34 +/- 4 vessels/mm(2)). Surprisingly, there was no significant difference in total osteoid between the two samples, suggesting that increased vascularization enhances mineralized tissue generation, but not necessarily osteoid formation. These results indicate that induced angiogenesis can enhance tissue regeneration, supporting the concept of therapeutic angiogenesis in tissue-engineering strategies.

Improved growth factor directed vascularization into fibrin constructs through inclusion of additional extracellular molecules

“…Prior studies have reported vascularizaton of tissue engineered constructs using both synthetic and naturally-derived constructs containing growth factors and/or cells (for examples see (Borges et al, 2003a;Borges et al, 2003b;Elcin and Elcin, 2006;Ganta et al, 2003;Kaigler et al, 2006;Murphy et al, 2004;Tanihara et al, 2001;Yao et al, 2004;Zisch et al, 2003)). However, the primary focus of these studies did not address the manner of directed vascular invasion into the matrix, but only upon the end extent of vacularization.…”

Regenerative medicine in orthopaedic surgery

“…For example, these materials can be designed to simultaneously provide osteoconductive surfaces to promote bone regeneration, while releasing angiogenic factors to drive neovascularization in the regenerating tissue. 65,66 In this context, it is important to recognize that an interplay between these material cues and other environmental signals will regulate the net cell and tissue response. The mechanical properties of synthetic ECM, for example, will regulate the ability of cells to rearrange adhesion peptides presented from the material, 52 and through their control of cell proliferation will regulate transfection of adherent cell populations.…”

Intérêt de l’utilisation de l’oxygénothérapie hyperbare en prévention de l’échec implantaire chez le patient irradié

“…Ils ont mis en évidence une diminution de la synthèse du facteur de croissance VEGF (vascular endothelial growth factor). Cette diminution pourrait être prévenue par l'utilisation de l'OHB [50], hypothèse qui a été corroborée par les travaux de Nussenbaum et al [51] et de Murphy et al [52]. La diminution de la synthèse du VEGF serait induite par un messager, l'HIF-1 (hypoxic inducing factor-1), activé par l'irradiation.…”