Influence of Lysine-Based Biomaterials on Fibroblast to Myofibroblast Differentiation

Fibrous encapsulation occurs as a result of implantation of devices such as pacemakers, artificial breast implants, and microencapsulated islet cells used in type 1 diabetes treatment. The foreign body response (FBR) is responsible for the development of a fibrous capsule, which is often detrimental to the function of the implanted device and therefore affected patients. One event leading to fibrous capsule formation is contraction of collagen by myofibroblasts. The objective of this project was to significantly reduce the thickness of the fibrous capsule by limiting fibroblast to myofibroblast differentiation. It was hypothesized that using lysine-based biomaterials with amidine-like functional group modifications would inhibit matrix metalloproteinase (MMP) activity, a precursor to myofibroblast formation. MMP Inhibition would impede cleavage of latent transforming growth factor beta (L-TGF-β) to transforming growth factor beta (TGF-β), a cytokine that stimulates fibroblast to myofibroblast differentiation. Cell staining was performed on NIH 3T3 fibroblasts cultured on each biomaterial and stimulated by L-TGF-β and TGF-β to evaluate material performance. Fibroblast viability was found to be >70% on each material. These biomaterials have potential for use as a coating of microencapsulated islet cells for diabetes therapy. This study is also important for furthering understanding of the biology involved in fibrous capsule formation.