SBIR Phase II: Development of Injectable, Enzyme-Degradable Poly(carboxybetaine) Hydrogel Formulations as Aesthetic and Surgical Tissue Fillers

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is the realization of a next-generation soft tissue filler. Fillers are used to replenish volumes left by surgical procedures, medical disorders, trauma, or aging. In this $6B global market, there is great need for a filler having superior longevity to the leading hyaluronic acid products, while also exhibiting better safety and reversibility than existing synthetic products. This project aims to commercialize a degradable zwitterionic hydrogel (DZH) filler formulation that meets these market demands to improve patient outcomes. In Phase I, the key features required for an innovative product were identified, and prototype DZH formulations achieving these benchmarks were successfully developed. The objectives in Phase II are to finalize the design and characterization of an initial product, evaluate its in vivo performance in preclinical studies, and establish manufacturing feasibility. The success of this project will form the basis for a sustainable business, and further enable the development and commercialization of many next-generation biomedical products and technologies. This project will prepare DZH formulations for commercial translation as a reversible dermal filler. Currently, all reversible fillers in the skin rejuvenation market are based on similar hyaluronic acid hydrogel architectures that disappoint patients with their poor longevity. The DZH architecture exhibits a unique set of properties that combine to represent a real innovation: these include significantly enhanced longevity, high biocompatibility, broadly tunable rheological properties such as viscosity and cohesivity, and complete reversibility. The proposed R&D activities are designed to bridge the gap between this proof-of-concept and an attractive initial product. These include (1) finalizing the formulation and developing analytical methods and quality benchmarks prerequisite to in vivo testing and manufacturing; (2) scaling the design and protocols for feasible GMP production, (3) performing initial biodistribution and excretion experiments in mice; and (4) conducting GLP preclinical toxicology studies based on ISO 10993 guidelines. It is anticipated these efforts will establish the safest, longest-lasting reversible filler available. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.