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

SBIR 第一阶段：开发可注射、酶可降解的聚（羧基甜菜碱）水凝胶制剂作为美容和手术组织填充剂

• 批准号: 1747283
• 负责人: Andrew Sinclair
• 金额: $ 22.5万
• 依托单位: Taproot Medical Technologies
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1747283&HistoricalAwards=false
• 关键词: SBIR; Phase; Development; Injectable; Enzyme

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.

该SBIR第一阶段项目旨在开发可降解的两性离子水凝胶(DZH)作为可注射软组织填充物。填充物用于补充外科手术、医疗疾病、创伤或衰老留下的体积。市场上非常需要一种具有比市场领先的透明质酸(HA)产品更长寿命的填充物，同时也比现有的合成产品表现出更好的安全性和可逆性。两性离子水凝胶具有独特的生物相容性、生理稳定性，可加工成可调谐的注射制剂。这个第一阶段项目的关键里程碑是实现概念验证DZH材料，这种材料可以用酶选择性和安全地降解，同时保持它们的差异化优势：生物兼容性、寿命和成本效益生产。DZH填充剂的成功商业化将为患者提供安全、持久、成本效益高和可逆的治疗方法，使这些填充物成为目前所有可用产品线的通用替代品。在价值数十亿美元的美容填充物市场上，一种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。该项目旨在展示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产品将成为治疗和美容应用的第一个通用、长期和可逆的组织填充物。具体地说，它们的生物兼容性、流变性、选择性降解性和美观效果必须达到或超过基准HA填充物，而它们的寿命必须比基准产品有重大改进。主要的研发活动是：(I)基于特定的凝胶网络结构合成和鉴定强效DZH候选物；(Ii)展示选择性DZH的降解性，并最大限度地减少组织特定的内源性酶的分解；以及(Iii)评估概念验证DZH填充物，以确保它们达到或超过HA产品的生物兼容性和粘弹性基准。DZH的生物相容性和选择性降解将在体外进行研究，为第二阶段的临床前体内研究做准备。