Controlled growth factor delivery from biodegradable hydrogel scaffolds for articular cartilage repair
Holland, Theresa A.
Mikos, Antonios G.
Doctor of Philosophy
The use of oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels as carriers of growth factors for articular cartilage repair has been investigated. In vitro release studies examined release of transforming growth factor-beta1 (TGF-beta1) directly from OPF hydrogels and also from gelatin microparticles encapsulated within these OPF networks. These studies showed that hydrogel mesh size and microparticle content can be altered to control growth factor release rates. In particular, sustained delivery of TGF-beta1 was achieved by utilizing microparticles as a secondary drug carrier within OPF hydrogels. An in vitro degradation study demonstrated that these microparticles also serve as digestible porogens to enhance material degradation in the presence of collagenase. Furthermore, in this environment, microparticle loading and crosslinking extent were shown to influence the rates of TGF-beta1 release and composite degradation. When utilized in the repair of rabbit osteochondral defects, OPF scaffolds were shown to undergo biocompatible degradation and to support healthy tissue in-growth. However, the incorporated TGF-beta1 was not shown to greatly influence tissue repair. Accordingly, further investigations examined these hydrogel systems as carriers of TGF-beta1 and/or insulin-like growth factor (IGF-1) since these growth factors have been shown to synergistically promote chondrocyte proliferation and cartilage extracellular matrix synthesis in vitro. Surprisingly, individual delivery of IGF-1 appeared to enhance cartilage repair in rabbit osteochondral defects when compared to untreated defects, but delivery of TGF-beta1 with or without IGF-1 had no effect. These findings illustrate that the in vitro effects of growth factors, including the synergistic actions of multiple factors, may not directly translate to the wound healing environment. Furthermore, this research demonstrates the utility of these hydrogel systems in studying the effectiveness of various growth factor delivery regimes in soft tissue repair.