Analysis of the osteoinductive capacity and angiogenicity of an in vitro generated extracellular matrix

In this study, the osteoinductive potential of an in vitro generated extracellular matrix (ECM) deposited by marrow stromal cells seeded onto titanium fiber mesh scaffolds and cultured in a flow perfusion bioreactor was investigated. Culture periods of 8, 12, and 16 days were selected to allow for different amounts of ECM deposition by the cells as well as ECM with varying degrees of maturity (Ti/ECM/d8, Ti/ECM/d12, and Ti/ECM/d16, respectively). These ECM-containing constructs were implanted intramuscularly in a rat animal model. After 56 days, histologic analysis of retrieved constructs revealed no bone formation in any of the implants. Surrounding many of the implants was a fibrous capsule, which was often interspersed with fat cells. Within the pore spaces, the predominant tissue response was the presence of blood vessels and young fibroblasts or fat cells. The number of blood vessels on a per area basis calculated from a histomorphometric analysis increased as a function of the amount of ECM within the implanted constructs, with a significant difference between Ti/ECM/d16 and plain Ti constructs. These results indicate that although an in vitro generated ECM alone may not induce bone formation at an ectopic site, its use may enhance the vascularization of implanted constructs.