AbstractsBiology & Animal Science

Skeletal reconstruction is a common challenge faced by orthopedic, dental, and maxillofacial surgeons. Although autogenous bone graft, which is the gold standard of grafting material, has excellent mechanical and biological properties, its scarcity and associated donor site morbidities limit its application in clinical settings. Allogeneic and xenogeneic bone grafts are advantageous due to their availability, but their use is complicated by their inferior osteogenic capacity and risk of transmitting infections. Synthetic bone grafts consisting of scaffold(s), cells, and/or growth factor(s) have emerged as a promising substitute for natural bone grafts for skeletal reconstruction. Consistent with the notion that osteogenesis and angiogenesis are coupled processes during embryogenic bone formation and postnatal bone healing, this thesis suggests that the transplantation of bone marrow derived osteoprogenitor cells (mesenchymal stromal/stem cells [MSC]) in combination with the delivery of angiogenic growth factor (vascular endothelial growth factor [VEGF]) can be utilized to improve bone regeneration. MSC were isolated from the bone marrow of 4-month-old C3H WT mice and expanded in vitro before being transplanted into recipient mice. The MSC transplantation alone was able to improve peri-implant bone regeneration and fixation of an implant in poor quality bone as shown in a mouse model of femoral implant osseointegration simulating human hip prostheses (Chapter III). A novel murine model was developed to investigate the reconstruction of large-sized defects, such as those left after tumor resection or arising from major traumatic injuries. The MSC that were seeded in a biomimetic collagen scaffold in vitro and transplanted into the large defect were unable to promote sufficient bone regeneration to restore skeletal integrity. When supplemented with a bolus dose of VEGF treatment, the MSC-seeded dense collagen scaffold exhibited a higher degree of vascularization and integration with the recipient bone, which accounted for the significantly greater bone formation in the defect and the promotion of defect healing (Chapter IV). In addition to the bolus injection, VEGF covalently tethered with a collagen sponge was able to increase angiogenesis and bone healing of a critical-sized rat mandibular defect as a model of reconstruction of a critical-sized bone defect in the maxillofacial area (Chapter V). MSC transplantation is a promising approach to improve the osseointegration of implants used in bone reconstruction. A tissue engineering approach (combining a collagen biomimetic scaffold, MSC and VEGF) is able to promote the repair of large-sized bone defects. Thus, preclinical studies using large animal models and clinical trials are warranted. La reconstruction squelettique représente un défi majeur auquel sont confrontés les chirurgiens orthopédiques, dentaires et maxillo-faciaux. L'autogreffe osseuse est la méthode standard en or en raison de ses hautes propriétés mécaniques et biologiques. Cependant, son utilisation…