Semi-synthetic Biomaterials for Skin Wound Healing

用于皮肤伤口愈合的半合成生物材料

• 批准号: 9889033
• 负责人: Yong Wang
• 金额: $ 48.99万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9889033
• 关键词: Affect; Area; Biocompatible Materials; Biological; CCL27 gene; Cells; Chemicals; Clinical; Cutaneous; Data; Development; Dinitrofluorobenzene; Environment; Epithelial; Epithelium; Evaluation; Exhibits; Fibrin; Fibrinogen; GPR2 gene; Homeostasis; Hybrids; Hydrogels; Hypersensitivity; Immune; Immune response; Immune system; Immunology; Infection; Infection Control; Inflammatory Response; Intestines; Invaded; Lead; Leishmania; Lymphoid Cell; Maintenance; Measures; Mechanics; Mediating; Methods; Modeling; Molecular; Nature; Organ; Outcome; Patients; Permeability; Pharmaceutical Preparations; Procedures; Proteins; Public Health; Quality of life; Recovery; Regenerative Medicine; Regulation; Regulatory T-Lymphocyte; Research; Role; Skin; Skin repair; Skin wound healing; Sterile coverings; Testing; Tissues; United States; Vascular Endothelial Growth Factors; Vascularization; Work; aptamer; assault; base; compliance behavior; controlled release; design; enhancing factor; immune activation; immune clearance; improved; insight; mechanical properties; microorganism; novel; oxygen transport; release factor; response; restoration; skin disorder; skin wound; socioeconomics; success; wound; wound bed; wound care; wound closure; wound dressing; wound healing

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.

项目概要 皮肤不仅仅是一个物理屏障。它还充当增强免疫的器官 针对环境中有害刺激和入侵微生物的反应。然而，先进的 伤口敷料的研究主要是通过血管化等机制来闭合伤口， 上皮化、收缩、感染控制或其组合。没有研究过两种敷料 主要功能是促进伤口闭合和免疫稳态。我们最近的结果（自然 免疫学 2016）表明 CCR10 (+) 先天淋巴细胞对于皮肤稳态很重要 调节，表明 CCL27/CCR10 轴是操纵皮肤免疫细胞的一个有希望的目标 体内平衡。因此，该项目的目标是研究一种新型半合成生物材料，用于受控 CCL27 和血管内皮生长因子 (VEGF) 的释放。 CCL27将用于促进免疫 体内平衡和 VEGF 将用于促进伤口闭合。为了实现这一目标，这种生物材料将 用适体进行功能化。适体的使用有望解决具有挑战性的矛盾 需要高渗透性才能将氧气和药物有效输送到创面床的情况，但 它限制了药物的持续释放。初步结果表明，高导磁材料 用适配体功能化可以持续释放 VEGF，从而加速伤口闭合。基于 根据这些令人信服的初步数据，拟议的研究旨在检验一个新假设： 适体介导的 VEGF 和 CCL27 释放将促进伤口闭合和免疫稳态 恢复皮肤的关键功能。具体目标包括1）半合成和表征 合成伤口敷料； 2）评估敷料调节免疫细胞的功能和 在组织、细胞和分子水平上促进伤口闭合； 3) 修复皮肤的评估 对抗有害刺激。皮肤伤口构成重大公共卫生问题，影响超过 7.7 美国每年有 100 万人。该项目的成功将为伤口开发开辟新途径 敷料，改善患者的生活质量，减轻皮肤沉重的社会经济负担 伤口。