A continuing effort exists to identify methods and mechanisms that can be exploited to enhance the biocompatibility of implanted prosthetic devices. My approach is based on the concept that the foreign body response, which ultimately leads to structural, mechanical, or functional implant failure, can be controlled by modifications in implant materials surface design and properties. Critical cellular components of the foreign body reaction are adherent macrophages and foreign body giant cells (FBGCs), and several functional capacities of these cells, including inflammatory and wound healing cytokine secretions, are influenced by material surface properties. In addition, it has been demonstrated float apoptosis, or intentional cell suicide, can be induced by imposing geometric constraints on other adherent cell types. Therefore, it is hypothesized that the presentation of different surface chemistries and geometric constraints to macrophages and FBGCs can be utilized to influence cytokine production and the induction of apoptosis by these cells. Both in vitro and in vivo model systems will be employed to address two specific aims arising from the hypothesis: First, I will evaluate the effects of different micropatterned surface chemistries and geometric constraints on the activation of macrophages and FBGCs for the production of inflammatory and wound healing cytokines. And, secondly, I will investigate the effects of micropatterned surface chemistries and geometric constraints on the induction of apoptosis of adherent macrophages and FBGCs.
