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

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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.