| Description |
Silk-elastinlike protein polymers (SELP) combine the solubility of mammalian elastin and the strength of silk to create systems that self-assemble into gels in response to environmental stimuli. Exquisite control over genetic structure allows for the engineering of protein-based polymers with molecular-level control over monomer sequence and polymer length. Precision control over sequence and length enables precise tailoring of structure to function in a predictable fashion. Properties such as gelation rate, mechanical rigidity, and network density are dictated by the ratio and sequence of silk and elastin motifs, polymer length, and concentration in solution. Leveraging these properties, we explored potential applications of SELP matrices to improve drug delivery and therapeutically redirect blood flow through targeted vascular occlusion. In this dissertation, we have explored and demonstrated the utility of in situ gelling SELP formulations in four distinct disease conditions, namely, radiation-induced proctitis (RIP), interstitial cystitis/painful bladder syndrome (IC/PBS), hypervascular tumors in the head and neck, and cerebral aneurysms (CA). While each of these diseases has unique etiologies, shortcomings in current treatment paradigms can be addressed using in situ gelling agents through either local delivery, reducing the clearance of a therapeutic compound, or through selectively producing a physical obstruction to blood flow. In RIP and IC/PBS, SELP-based delivery systems demonstrated improved accumulation of a semisynthetic glycosaminoglycan ether therapeutic in epithelial tissues, significantly iv decreasing pain, and ameliorating local inflammatory responses. For hypervascular tumors and CA, we demonstrated injectability through clinical microcatheters, selective embolization, and a high degree of biocompatibility that facilitates vascular repair in CA. |
