Tissue engineering is a multidisciplinary field characterized by the application of engineering principles to the development, repair, and study of biological tissues. The manufacture of large-scale tissue engineered bone substitutes that are mechanically competent, easily vascularized, and support new bone formation requires an understanding of the effects of chemical and mechanical stimuli on osteoblast mineralization as well as factors which affect integration of the graft as a whole. Thus, the goal of this dissertation was to investigate the effects of basic fibroblast growth factor (bFGF) and flow-induced shear stresses on bone cell mineralization, and the permeability of various graft materials.

Basic fibroblast growth factor stimulates osteoblast proliferation and differentiation. Treatment with 5 ng/ml of bFGF for the first 7 days of culture accelerated the mineralization of osteoprogenitor cells and the resulting mineral was chemically similar to intact bone. These data indicate that bFGF has potential for generating large amounts of mineral in vitro which can then be used to form a biological composite or, hybrid, bone substitute.

The anabolic response of osteoblasts to pulsatile shear stress was examined using a parallel plate flow chamber. After 7 days of exposure to 0.6 dynes/cm² or 6.0 dynes/cm² there was no change in proliferation or mineralization compared to static controls. Thus, the effects of pulsatile fluid flow are negligible when compared to those of the chemical environment.

The successful integration of bone grafts depends largely on their permeability. In trabecular bone it ranges over three orders of magnitude and depends on anatomic site and flow direction. Over the range of porosities reported here and in the literature, the Kozeny model was the best predictor of permeability and, consequently, the most useful from a design perspective.

These data can be combined with analytical models to design a large-scale bone substitute consisting of a biocompatible frame seeded with mineralizing bone marrow stromal cells. Based on the initial geometry and thickness of the mineral layer, the permeability and mechanical properties can be predicted via Kozeny and cellular solid models, respectively. While there are still many unanswered questions these studies support the feasibility of hybrid bone substitutes.