Therapeutic cells encapsulation and delivery for improved healing of chronic diabetic wounds

第一阶段SBIR提案的目标是证明可流动的抗菌细胞的可行性 用于改善清洁和病原体污染的糖尿病患者的组织再生的递送载体 伤口糖尿病溃疡是公共卫生和经济的主要负担，因为它们占至少33%， 在美国每年1160亿美元的直接糖尿病医疗费用中。预计这一负担将 在不久的将来增加，因为据估计，糖尿病在美国的患病率，目前在 9.3%，到2050年可能达到三分之一的成年人。糖尿病伤口愈合延迟并发感染是糖尿病的主要并发症。 非创伤性下肢截肢的主要原因，每年约有10万例。 申报产品将通过以下方式将治疗性细胞输送到有感染风险的糖尿病伤口中：（i） 允许简单的即时细胞包封和应用于伤口床（ii）提供细胞外 （iii）促进移植细胞的保留和存活力的细胞支架基质， 通过固有的广谱抗菌活性来防止污染。申报产品预期用于 由医疗保健专业人员在外科伤口清创手术后使用。 为了确定该产品的可行性，我们提出了以下两个具体目标： 具体目标1：评价凝胶制剂有效包封治疗性细胞的能力， 支持体内细胞活力。 Milcobacterium：在体外和体内在凝胶中包封后显示治疗性细胞的高活力。 具体目标2：证明递送治疗性细胞的凝胶用于促进改善的细胞毒性的体内功效。 糖尿病小鼠中全层清洁和病原体污染伤口的愈合。 Mildrone：在第14天和第28天显示加速的伤口愈合和改善的再生组织质量。 在II期SBIR研究中，我们将在糖尿病猪伤口愈合模型中验证产品， GMP生产，并执行GLP研究，为FDA提交前讨论做准备。

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.