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

This SBIR Phase I project aims to develop degradable zwitterionic hydrogels (DZH) as injectable soft tissue fillers. Fillers are used to replenish volumes left by surgical procedures, medical disorders, trauma, or aging. There is great need for a filler featuring superior longevity to the market-leading hyaluronic acid (HA) products, while also exhibiting better safety and reversibility than existing synthetic products. Zwitterionic hydrogels are uniquely biocompatible, physiologically stable, and can be processed into tunable injectable formulations. The key milestone targeted in this Phase I project is the achievement of proof-of-concept DZH materials that can be selectively and safely degraded with enzymes while maintaining their differentiating strengths: biocompatibility, longevity, and cost-effective production. Successful commercialization of DZH fillers will provide patients with a safe, long-lasting, cost-effective, and reversible treatment, positioning these fillers as a universal replacement for all currently available product lines. A disruptive product in the multibillion-dollar aesthetic filler market would form a solid basis for a sustainable business and ultimately enable the development and commercialization of many next-generation biomedical products. This project intends to show that DZH formulations based on zwitterionic polymers can meet key requirements of a next-generation injectable tissue filler. If technical targets are met, DZH products will be transformative as the first universal, long-term, and reversible tissue fillers for therapeutic and aesthetic applications. Specifically, their biocompatibility, rheological properties, selective degradability and aesthetic outcomes must meet or exceed the benchmark HA fillers, while their longevity must show key improvement over benchmark products. The main R&D activities are: (I) synthesizing and identifying strong DZH candidates based on particular gel network architectures; (II) demonstrating selective DZH degradability with minimal breakdown by tissue-specific endogenous enzymes; and (III) evaluating proof-of-concept DZH fillers to ensure they meet or exceed the biocompatibility and viscoelasticity benchmarks of HA products. DZH biocompatibility and selective degradation will be studied in vitro to prepare for preclinical in vivo studies in Phase II.