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.

该创新-技术转化伙伴关系（PFI-TT）项目的更广泛影响/商业潜力在于，它可能导致开发可注射的植物基材料，以替代因疾病而丧失的人类软组织（即，癌症）、创伤或遗传性出生缺陷。 几种天然和合成材料已在临床上用于长期组织替代，但都有局限性，包括成本、安全性、作用持续时间以及在发生并发症时缺乏可逆性。在美国，每年进行超过430，000次组织置换手术，涉及市售的半永久性填充物和脂肪移植物，成本超过3.95亿美元，通常结果不令人满意。 本申请旨在从植物中发现的天然糖中设计稳定但可逆的可注射软组织填充材料。该项目的成功完成将产生有价值的概念验证数据，证明这些植物源生物材料在人体试验之前在小动物模型中的安全性和有效性。 因此，拟议的研究有可能改善患有各种需要安全稳定的组织填充材料的疾病的个人的生活质量。拟议的项目重点是将一种源自植物多糖纤维素的新型可注射生物材料用于人类长期软组织重建。老化、创伤和疾病通常会导致真皮胶原蛋白和脂肪的损失，从而在软组织中产生缺陷。 因此，需要开发安全有效地恢复枯竭地区的材料。甲基纤维素（MC）是FDA批准的水溶性纤维素衍生物，具有生物相容性且价格低廉。与易受酶活性影响的其他天然生物材料填料相比，人体中不存在纤维素消化酶纤维素酶可改善MC在体内的保留和机械稳定性。该提案将研究在原位凝胶MC水凝胶的长期稳定性，在小动物软组织缺损模型中通过双重热凝胶化和氧化还原引发的交联机制来稳定。研究设计还将探索使用纤维素酶给药安全且容易地降解MC凝胶以纠正不良结局。无需手术切除即可取出可注射的长期植入物将非常有利于临床转化;此外，可逆性的证明将在这一市场空间提供明显的竞争优势。该奖项反映了NSF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。