Semi-synthetic Biomaterials for Skin Wound Healing

项目摘要 皮肤不仅仅是一道物理屏障。它也起到了免疫器官的作用。 对有害刺激和入侵环境微生物的反应。但是，高级 伤口敷料的研究主要是通过血管形成等机制来关闭伤口， 上皮化、收缩、感染控制或它们的组合。还没有用两种调料进行过研究 促进伤口愈合和免疫动态平衡的主要功能。我们的最新研究结果(《自然》 免疫学2016)表明CCR10(+)先天淋巴样细胞对皮肤动态平衡很重要 CCL27/CCR10轴的调节，表明CCL27/CCR10轴是操纵皮肤免疫细胞的一个有前途的靶点 动态平衡。因此，本项目的目标是研究一种新型的可控半合成生物材料。 释放CCL27和血管内皮生长因子(VEGF)。CCL27将用于促进免疫 动态平衡和血管内皮生长因子将用于促进伤口闭合。为了实现这一目标，这种生物材料将 用适配子功能化。适体的使用有望解决一个具有挑战性的矛盾。 需要高渗透性才能有效地将氧气和药物输送到伤口床的情况，但 它限制了药物的持续释放。初步结果表明，高渗透材料 适体功能化可以持续释放血管内皮生长因子，加速伤口闭合。基座 基于这些令人信服的初步数据，拟议的研究旨在检验一个新的假设，即 适体介导的血管内皮生长因子和CCL27的释放将促进伤口闭合和免疫动态平衡 恢复皮肤的主要功能。具体目标包括：1)合成和表征半-羟基-4-羟基-4-羟基-4-羟基-4-羟基-4-羟基-4-羟基-4-羟基-4 合成创面敷料；2)评价敷料调节免疫细胞和 在组织、细胞和分子水平促进伤口闭合；以及3)对修复的皮肤进行评估 防止有害的刺激。皮肤创伤是一个主要的公共卫生问题，影响到超过7.7 美国每年有一百万人。该项目的成功将为创伤的发展开辟一条新的道路 敷料，提高患者的生活质量，减轻沉重的皮肤社会经济负担 伤口。

Project Summary Skin works as more than a physical barrier. It also functions as an organ mounting the immune responses against harmful stimulations and invading microorganisms of the environment. However, advanced wound dressings have been studied primarily for wound closure through mechanisms such as vascularization, epithelialization, contraction, infection control or their combinations. No dressings have been studied with two primary functions of promoting both wound closure and immune homeostasis. Our recent results (Nature Immunology 2016) have shown that CCR10 (+) innate lymphoid cells are important for cutaneous homeostatic regulation, suggesting that the CCL27/CCR10 axis is a promising target in manipulating immune cells for skin homeostasis. Thus, the objective of this project is to study a novel semi-synthetic biomaterial for controlled release of CCL27 and vascular endothelial growth factor (VEGF). CCL27 will be used to promote immune homeostasis and VEGF will be used to promote wound closure. To achieve this objective, this biomaterial will be functionalized with aptamers. The use of aptamers is promising to solve a challenging contradictory situation where high permeability is necessary for efficient transport of oxygen and drugs to the wound bed but it limits sustained drug release. The preliminary results have demonstrated that highly permeable materials functionalized with aptamers can release VEGF in a sustained manner for accelerated wound closure. Based on these compelling preliminary data, the proposed research is aimed at testing a novel hypothesis that aptamer-mediated release of VEGF and CCL27 will promote both wound closure and immune homeostasis to restore the key functions of the skin. Specific aims include 1) synthesis and characterization of the semi- synthetic wound dressing; 2) evaluation of the functions of the dressing in regulating immune cells and promoting wound closure at the tissue, cellular and molecular levels; and 3) evaluation of the repaired skin against harmful stimulations. Skin wounds constitute a major public health problem, affecting more than 7.7 million people in the U.S. every year. The success of this project will open a new avenue of developing wound dressings, improve the quality of the lives of patients and reduce the heavy socioeconomic burden of skin wounds.