The goal of this Phase I SBIR proposal is to demonstrate feasibility of a flowable, antimicrobial cell delivery vehicle for improving tissue regeneration in clean and pathogen-contaminated diabetic wounds. Diabetic ulcers are a major burden on public health and the economy, as they represent least 33 % of the annual $116 billion in direct diabetic health care cost in the United States. This burden is projected to increase in the near future, since it is estimated that the prevalence of diabetes in the US, which is currently at 9.3%, could reach up to 1 in 3 adults by 2050. Delayed diabetic wound healing complicated by infection is the primary cause of non-traumatic lower-limb amputations, representing ~100,000 cases annually. The proposed product will deliver therapeutic cells into diabetic wounds that are at risk for infection by (i) allowing simple, point-of-care cell encapsulation and application to wound beds (ii) providing an extracellular cell scaffolding matrix that promotes retention and viability of transplanted cells (iii) preventing pathogenic contamination through intrinsic, broad-spectrum antimicrobial activity. The proposed product is intended for use by healthcare professionals following surgical wound debridement procedures. To establish feasibility for this product, we propose the following two specific aims:
Specific Aim 1 : Evaluate gel formulations for their ability to effectively encapsulate therapeutic cells and support cell viability in vivo. Milestones: Show high viability of therapeutic cells following encapsulation in gels both in vitro and in vivo.
Specific Aim 2 : Demonstrate in vivo efficacy of gels delivering therapeutic cells for promoting improved healing of full-thickness clean and pathogen-contaminated wounds in diabetic mice. Milestones: Show accelerated wound healing and improved quality of regenerated tissue at days 14 and 28. In Phase II SBIR studies, we will validate the product in a diabetic swine model of wound healing, establish GMP manufacturing, and execute GLP studies in preparation for an FDA pre-submission discussion.
The proposed product is a flowable antimicrobial cell scaffolding matrix that will deliver therapeutic cells into chronic diabetic wounds, which are challenging to treat and prone to infections, in order to promote regrowth of patient tissue and wound closure. The product is designed to incorporate three beneficial features in one material: simple point of care cell encapsulation and wound application, support for transplanted cells, and resistance to pathogenic colonization. This product is intended for intra-operative use following surgical wound debridement procedures, and it has the potential to mitigate the 100,000 amputations, 1.7 million infections, and 99,000 deaths associated with poor wound closure and antibiotic resistance annually.
