UCSF

This dissertation focuses on two aspects that present challenges for a broad range of implantable devices and transplants - blood compatibility and wound healing properties of biomaterials. In the first chapter, we examined the hemocompatibility of surface modified silicon substrates used in renal replacement devices. Our reports showed that the polymer conjugated silicon samples reduced platelet attachment and activation to levels comparable to that on Teflon, a material commonly used in medical implant devices. Our findings suggest that surface modified silicon substrates could be used to develop miniaturized implants for renal replacement therapies.

In the second chapter, we investigated how collagen nanotopography affects wound healing in the cornea. The presence of nanopatterned collagen fibrils was shown to promote the appearance of the healthy keratocyte phenotype and attenuate the fibrotic myofibroblast phenotype. In addition, collagen nanotopography also had an effect on matrix synthesis. These results have significant implications for the design of tissue engineered corneal substitutes and for promoting regenerative wound healing in the cornea.

In the third chapter, we focused on wound healing in the skin, particularly in the case of keloid scars. Keloids are locally aggressive dermal scars formed as a result of abnormal wound healing. They are characterized by excessive fibroblast proliferation and matrix production. An effective treatment for keloids is yet to be established due to a high rate of recurrence. Our results showed that collagen fibril alignment reduced cell proliferation and matrix synthesis in fibroblasts derived from keloid, scar and healthy dermal tissue. This data suggests that aligned collagen fibrils could be used to develop dermal patches that reduce the recurrence of keloids and aid in the design of an effective therapy for keloid management. The recurring theme in both the cornea and keloid studies is that matrix architecture could be used to effectively manipulate cell response to direct regenerative wound healing. Collectively our findings show that physical cues such as matrix topography could be used to improve the anti-fibrotic properties of biomaterials and aid in the design of tissue engineered implants for various clinical applications.