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

该第一阶段SBIR提案的目标是证明可流动的抗微生物细胞的可行性 清洁和病原体污染的糖尿病患者促进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，因为它们至少占33% 在美国每年1160亿美元的直接糖尿病医疗费用中。这一负担预计将 在不久的将来会增加，因为据估计，美国的糖尿病患病率目前为 9.3%，到2050年可能达到三分之一的成年人。合并感染的糖尿病伤口延迟愈合是 非创伤性下肢截肢的主要原因，每年约有100,000例。 拟议的产品将把治疗细胞输送到糖尿病创面，这些创面有感染的风险(I) 允许简单的护理点细胞封装并应用于伤口床(Ii)提供细胞外 促进移植细胞保留和存活的细胞支架基质(III)防止致病 通过固有的广谱抗菌活性造成的污染。建议的产品的目标是 医疗保健专业人员在手术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：评估凝胶制剂有效包裹治疗细胞和 支持细胞在体内的存活。 里程碑：在体外和体内，治疗细胞在凝胶中包裹后显示出高活性。 具体目标2：展示凝胶输送治疗细胞促进改善的体内效果 糖尿病小鼠全层清洁和病原体污染伤口的愈合。 里程碑：在第14天和第28天显示创面加速愈合和再生组织质量改善。 在第二阶段的SBIR研究中，我们将在糖尿病猪的伤口愈合模型中验证该产品，建立 GMP生产，并执行GLP研究，为FDA提交前的讨论做准备。

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.