Multifunctional dressing for treatment of diabetic wounds

项目摘要 慢性糖尿病伤口（CDW）是最具挑战性和最常见的2型糖尿病并发症之一 糖尿病CDW与医疗保健系统和社会的成本显著增加有关， 患者生活质量下降，合并症（如复发性感染）发生率较高， 截肢，以及整体显著更高的死亡率。2型糖尿病的广泛流行及其 不断增加的影响迫切需要有效的治疗，旨在恢复 CDW的生理愈合和预防相关的共病和死亡。皮肤不足 血管化和感染抑制CDW的有效愈合。在非糖尿病损伤中，生理愈合 依赖于新血管生成和血管化来恢复组织氧合，提供代谢支持， 再生细胞/组织，并允许免疫细胞迁移以抵抗病原体。相反，在CDW中， 血管生成受损，导致组织缺氧，缺乏组织修复所需的代谢支持， 以及对细菌感染的免疫反应不足。这些条件首先“锁定”CDW在慢性 炎症状态不能进展到组织修复，其次使患者处于脓毒症的风险中。严重 例，手术清创或截肢是挽救患者生命的唯一选择。我们的假设是 VEGF（一种血管生成因子）、氧气与抗生素按需释放的结合， 对中性粒细胞分泌体上调的反应可以防止生物膜形成， CDW发病率。这项提案的目标是设计包含微针阵列的绷带 其可以控制VEGF、氧气的释放，并且可以对细菌介导的 中性粒细胞分泌体，用于诱导愈合和避免感染。

PROJECT SUMMARY Chronic diabetic wounds (CDW) are one of the most challenging and common medical complications of type-2 diabetes. CDWs are associated with significantly increased costs for healthcare systems and society, decreased quality of life for patients, higher rates of co-morbidities such as recurrent infections and amputations, and an overall dramatically higher mortality rate. The wide prevalence of type-2 diabetes and its constantly increasing impact urgently demand the need for effective treatments aimed at restoring physiological healing of CDWs and preventing associated co-morbidities and mortality. Insufficient skin vascularization and infection inhibit effective healing of CDWs. In non-diabetic injuries, physiologic healing relies on neoangiogenesis and vascularization to restore tissue oxygenation, provide metabolic support to regenerating cells/tissues, and to allow migration of immune cells to counteract pathogens. Instead, in CDWs angiogenesis is impaired resulting in tissue hypoxia, lack of the metabolic support required for tissue repair, and an insufficient immune-response to bacterial infections. These conditions first “lock” CDWs in a chronic inflammatory state unable to progress to tissue repair and second place the patients at risk of sepsis. In severe cases, surgical debridement or limb amputation is the only option for saving patients’ lives. Our hypothesis is that the delivery of VEGF (an angiogenic factor), oxygen combined with on demand release of antibiotics in response to upregulation of neutrophil secretomes can prevent biofilm formation and in turn can reduce the CDW morbidity rate. The goal of this proposal is to engineer bandages containing microneedle arrays that can control release VEGF, oxygen, and can self respond to upregulation of bacteria mediated neutrophil secretomes for inducing healing and avoiding infection.