Controlled In Vivo Mechanical Stimulation of Bone Repair Constructs

Bone grafts are used to treat more than 300,000 fracture patients yearly, as well as patients with congenital defects, bone tumors, and those undergoing spinal fusion. Given the established limitations of autograft and allograft bone, there is a substantial need for bone graft substitutes. Tissue engineering strategies employing the addition of osteogenic cells and/or osteoinductive factors to porous scaffolds represent a promising alternative to traditional bone grafts. While many bone defects are in load-bearing sites, very little is known about the response of bone grafts and their substitutes to mechanical loading, despite vast documentation on the ability of normal bone to adapt to its mechanical environment. The goal of this research was to quantify the effects of controlled in vivo mechanical stimulation on bone graft repair and bone graft substitutes and identify the local stress/strain environment associated with load-induced changes in bone formation. The global hypothesis that cyclic in vivo mechanical loading improves mineralized matrix formation within bone grafts and bone graft substitutes was addressed in this work using orthotopic and ectopic models specifically designed to facilitate modeling of local stresses and strains. In the first study, a bone defect repair model utilizing an orthotopic implant capable of supplying a controlled mechanical stimulus to a trabecular allograft showed a significant reduction in new bone formation with controlled in vivo mechanical loading. Although the reason remains unclear, loading conditions may not have been ideal for increased bone formation or potential micromotion may have influenced the results. A second study demonstrated for the first time that controlled in vivo mechanical stimulation enhances mineralized matrix production on a mesenchymal stem cell-seeded polymeric construct using a novel subcutaneous implant system. In addition, the local stresses and strains associated with this adaptive response were predicted. The novel subcutaneous implant represents technology which may be adapted for the preparation of tissue-engineered bone constructs, capitalizing on the benefits of mechanical loading and a vascularized in vivo environment. Such an approach may produce larger, stronger, and more homogeneous constructs than could be developed in a static culture system subject to diffusional limitations.Ph.D