UCSF

Understanding material-host interactions is critical to designing and characterizing biomaterials for use in medical implants. From joint replacements, to pacemakers, to artificial hearts, all surfaces that contact the body require thorough characterization and optimization to elicit an appropriate response in the body. This dissertation discusses the applications of biomaterials for two distinct clinical needs: ocular drug delivery, and vascular stenting.

The first part of this dissertation discusses the surface engineering of titanium implants by fabricating TiO¬2 nanotube coatings. First, Chapter 1 provides an overview of the uses of TiO2 nanotubes for applications in tissue engineering, smart drug release platforms, and biosensing. Then, Chapter 2 is a mechanistic study of titania nanotube topography as a surface coating for vascular stents. In this study, we investigated how nanotopographical cues on the stent surface can modulate vascular phenotype, with the goal of developing an alternative strategy to drug-eluting stents (DES) for decreasing restenosis. We demonstrated that nanotube topography can decrease SMC surface coverage without affecting endothelialization. In addition, to our knowledge, this is the first study reporting that TiO¬¬2 nanotube topography dampens the response to inflammatory cytokine stimulation in endothelial and smooth muscle cells.

The second part of this work addresses the clinical need for long-acting intraocular drug delivery implants. Chapter 3 is a survey of recent advances in long-acting, sustained-release intraocular implants, highlighting the recent developments spanning the pre-clinical, clinical, and post-FDA approval stages. Then, Chapter 4 is a report of the design, characterization, and in vivo validation of a drug delivery implant for the treatment of glaucoma. Eye drop administration is the current gold standard, but patient noncompliance is an obstacle to efficacious treatment. We designed a polymeric implant to co-deliver two hypotensive agents, achieving independently controlled zero-order release of timolol maleate and brimonidine tartrate. We also demonstrated IOP-lowering effects of the implant for three months in vivo. Taken together, these projects seek to contribute to the continued expansion and development of the biomaterials field and its applications in medicine.