Engineered bone grafting has been considered as one of the alternative methods for bone regeneration in both fundamental research and clinical applications to address bone disorders. Bone graft materials, autologous bone, allogeneic bone and synthetic polymer scaffolds have been commonly utilized surgically as substrates for bone grafting. In this dissertation, periosteum, a thin membrane in which progenitor cells can develop into osteoblasts to regenerate bone tissue, has been applied in three different studies to determine its capability to induce new bone formation.

In the first study, human periosteum-wrapped bone allografts were implanted subcutaneously in athymic mice followed by sample harvest and gene expression analysis and histological assessment. The second study developed a tissue-engineering approach to generate a functional tendon-to-bone enthesis. In this instance, the constructs were fabricated from human periosteum-wrapped allograft bone and tenocyte- and chondrocyte-seeded biomaterials. The constructs were then implanted with and without mechanical force by either tethering them to the trapezius and gluteus maximus muscles of athymic mice or not tethering them at all. Biomechanical, histological, and histochemical properties of these tendon-to-bone enthesis models were analyzed following their implantation. The third study was designed to determine the possible effects of bromine- or silicon-functionalized poly(lactic acid) (Si-PLA) scaffolds on skeletal development. To examine initially the cytotoxicity of bromine on periosteal cells, a PrestoBlue® assay was performed on human periosteal cell-seeded brominated PLA scaffolds over a 21-day time period.

With application of histological and gene expression analysis, new bone formation and resorption were detected in human-periosteum allografts implanted for different time periods. Correlated histological and gene data showed that periosteum has the capability of inducing bone regeneration in allografts and in tendon-to-bone enthesis models. Tissue-engineered enthesis models fabricated with periosteum-allograft and chondrocyte- and tenocyte-seeded scaffolds provide a novel method for healing enthesis defects in regenerative medicine. In addition, results from bromine cytotoxicity studies of human periosteal cells imply subsequent Si-PLA experiments with minimal numbers of bromine residues on the backbone of PLA. These tissue engineering investigations suggest that both allograft bone and biosynthetic polymers have great potential in regenerative medicine applications for bone.