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

这个小企业创新研究（SBIR）二期项目的更广泛的影响/商业潜力是实现下一代软组织填充物。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。在这个价值60亿美元的全球市场中，迫切需要一种比领先的透明质酸产品寿命更长，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。该项目旨在商业化可降解两性离子水凝胶（DZH）填充剂配方，以满足这些市场需求，改善患者的治疗效果。在第一阶段，确定了创新产品所需的关键特性，并成功开发了达到这些基准的DZH原型配方。II期的目标是完成初始产品的设计和表征，在临床前研究中评估其体内性能，并确定生产可行性。该项目的成功将为可持续发展的业务奠定基础，并进一步推动许多下一代生物医学产品和技术的开发和商业化。该项目将制备DZH配方作为可逆真皮填充剂用于商业翻译。目前，皮肤再生市场上所有可逆性填充剂都是基于类似的透明质酸水凝胶结构，这让患者失望，因为它们的寿命不长。DZH结构展示了一组独特的特性，这些特性结合起来代表了真正的创新：这些特性包括显着延长的寿命，高生物相容性，广泛可调的流变特性，如粘度和黏性，以及完全可逆性。拟议的研发活动旨在弥合概念验证和有吸引力的初始产品之间的差距。这些包括(1)确定制剂和开发体内测试和生产的先决条件的分析方法和质量基准；(2)确定可行的GMP生产的设计和方案；(3)在小鼠身上进行初步的生物分布和排泄实验；(4)根据ISO 10993指南进行GLP临床前毒理学研究。预计这些努力将建立最安全，最持久的可逆填料。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.