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

SBIR一期项目旨在开发可降解两性离子水凝胶（DZH）作为可注射的软组织填充物。填充物用于补充外科手术、医学疾病、创伤或衰老留下的体积。对于一种比市场领先的透明质酸（HA）产品寿命更长，同时比现有合成产品具有更好的安全性和可逆性的填充剂的需求很大。两性离子水凝胶具有独特的生物相容性，生理稳定性，可以加工成可调的注射制剂。第一阶段项目的关键里程碑是实现DZH材料的概念验证，这种材料可以被酶选择性和安全地降解，同时保持其独特的优势：生物相容性、寿命和成本效益。DZH填充物的成功商业化将为患者提供安全、持久、经济、可逆的治疗，将这些填充物定位为所有现有产品线的通用替代品。在数十亿美元的美容填充物市场中，一个颠覆性的产品将为可持续发展的业务奠定坚实的基础，并最终使许多下一代生物医学产品的开发和商业化成为可能。该项目旨在表明，基于两性离子聚合物的DZH配方可以满足下一代可注射组织填充物的关键要求。如果达到技术目标，DZH产品将成为第一种通用的、长期的、可逆的组织填充物，用于治疗和美容应用。具体来说，它们的生物相容性、流变性、选择性降解性和美观性必须达到或超过基准HA填充剂，而它们的寿命必须比基准产品有重大改善。主要研发活动包括：(1)基于特定凝胶网络结构合成和鉴定强DZH候选物；（II）证明DZH可选择性降解，组织特异性内源性酶的分解最小；（III）评估DZH填充物的概念验证，以确保它们达到或超过HA产品的生物相容性和粘弹性基准。DZH的生物相容性和选择性降解将在体外进行研究，为II期临床前体内研究做准备。

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.