PFI-TT: Injectable Cellulose-Based Hydrogels for Soft Tissue Bulking

PFI-TT：用于软组织膨胀的可注射纤维素水凝胶

• 批准号: 2214012
• 负责人: Steven Nicoll
• 金额: $ 25万
• 依托单位: CUNY City College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2214012&HistoricalAwards=false
• 关键词: PFI; TT; Injectable; Cellulose; Based

The broader impact/commercial potential of this Partnerships for Innovation - Technology Translation (PFI-TT) project is that it may lead to the development of injectable, plant-based materials to replace human soft tissues lost due to disease (i.e., cancer), trauma, or inherited birth defects. Several natural and synthetic materials have been used clinically for long-term tissue replacement, but all have limitations, which include cost, safety, duration of effect, and lack of reversibility in the event of complications. Over 430,000 tissue replacement procedures are performed in the United States annually involving commercially available semi-permanent fillers and fat grafts at a cost of over $395 million, often with unsatisfactory results. The present application aims to engineer a stable, yet reversible, injectable, soft tissue filler material from the natural sugars found in plants. Successful completion of the project will result in valuable proof-of-concept data demonstrating the safety and efficacy of these plant-derived biomaterials in a small animal model, in advance of human trials. As such, the proposed studies have the potential to improve the quality of life for individuals suffering from a variety of conditions requiring safe and stable tissue bulking materials.The proposed project focuses on translating a novel injectable biomaterial derived from the plant polysaccharide, cellulose, for long-term soft tissue reconstruction in humans. Aging, trauma, and disease often result in the loss of dermal collagen and fat, producing a deficit in the soft tissue. As a result, there is the need to develop materials that safely and effectively restore areas of depletion. Methylcellulose (MC) is an FDA-approved, water-soluble, cellulose derivative that is biocompatible and inexpensive. The absence of the cellulose-digesting enzyme, cellulase, in humans affords improved retention and mechanical stability of MC in vivo, in comparison to other natural biomaterial fillers that are susceptible to enzymatic activity. This proposal will examine the long-term stability of in situ gelling MC hydrogels stabilized by dual thermal gelation and redox-initiated crosslinking mechanisms in a small animal soft tissue deficit model. The study design will also explore the use of cellulase administration to safely and easily degrade the MC gels to correct for adverse outcomes. Removal of injectable long-term implants without the need for surgical excision would be highly beneficial for clinical translation; Moreover, demonstration of reversibility will provide a distinct advantage over competitors in this market space.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.

这种创新合作伙伴关系的更广泛的影响/商业潜力 - 技术翻译（PFI-TT）项目可能导致开发可注射植物性的材料，以取代因疾病（即癌症），癌症而失去的人类软组织创伤或继承的先天缺陷。 几种天然和合成的材料已在临床上用于长期置换，但都有局限性，其中包括成本，安全性，效果持续时间以及在并发症时缺乏可逆性。每年在美国进行超过430,000个组织置换程序，涉及市售的半永久性填充剂和脂肪移植物，成本超过3.95亿美元，通常会产生不令人满意的结果。 目前的应用旨在设计一种植物中天然糖的稳定，可逆的，可逆的，可注射的软组织填充物的材料。该项目的成功完成将导致有价值的概念验证数据，证明在人类试验之前，在小型动物模型中这些植物衍生的生物材料的安全性和功效。 因此，拟议的研究有可能改善患有各种条件的人的生活质量，需要安全，稳定的组织散装材料。拟议的项目着重于翻译源自植物多糖，纤维素的新型可注入的生物材料，用于用于，用于人类的长期软组织重建。衰老，创伤和疾病通常会导致皮肤胶原蛋白和脂肪的损失，从而导致软组织缺乏。 结果，有必要开发安全有效地恢复耗竭区域的材料。甲基纤维素（MC）是一种由FDA批准的，水溶性的纤维素衍生物，具有生物相容性且廉价的。与易受酶促活性的其他天然生物材料填充剂相比，人类中纤维素消化酶的缺乏可改善MC在体内的保留率和机械稳定性。该提案将研究通过小动物软组织不足模型中双重热胶凝和氧化还原引发的交联机制稳定的原位胶凝MC水凝胶的长期稳定性。研究设计还将探索使用纤维素酶给药以安全，轻松降解MC凝胶以纠正不良结果。消除无需手术切除的无需手术切除的可注射长期植入物将对临床翻译非常有益；此外，可逆性的演示将为这个市场领域中的竞争对手提供明显的优势。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来获得支持。