Injectable High Viscosity Liquid Carriers for Bone Tissue Engineering

Abstract

The clinical management of critical sized defects and traumatic bone injuries continues to challenge the orthopaedic field. The gold standard of treatment uses autologous bone grafting to promote repair. While effective in many cases, donor site morbidity is a common complication. The field of bone tissue engineering aims to develop viable alternatives to autologous bone graft. The bone graft substitute INFUSE® (bone morphogenetic protein-2 [BMP-2] in acellular collagen sponge) is currently in clinical use, however we and others have hypothesized that the collagen delivery system is suboptimal. This thesis aims to develop high viscosity sugar-based carriers as alternative delivery systems for BMP-2. Initial studies utilise sucrose acetate isobutyrate (SAIB), already in clinical trials for drug delivery. Rodent implantation and fracture models were used to compare SAIB for BMP-2 delivery as well as other adjunctive agents. SAIB/BMP-2 was also trialled in a pig model of hip osteonecrosis. Novel sugar-based carriers were developed using polycondensation and esterification and tested for biocompatibility and in vivo BMP-2 delivery. These studies represent an innovative approach to bone tissue engineering with multiple clinical applications.