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.

项目摘要 皮肤不仅仅是一个物理屏障。它也作为一个器官安装免疫 对环境中有害刺激和入侵微生物的反应。然而，先进的 伤口敷料已经被研究主要用于通过诸如血管形成的机制进行伤口闭合， 上皮形成、收缩、感染控制或它们的组合。没有研究过两种敷料 促进伤口闭合和免疫稳态的主要功能。我们最近的结果（自然 Immunology 2016）已经表明，CCR 10（+）先天淋巴细胞对皮肤稳态很重要， 调节，表明CCL 27/CCR 10轴是操纵皮肤免疫细胞的有希望的靶点。 体内平衡因此，本项目的目标是研究一种新型半合成生物材料，用于控制 CCL 27和血管内皮生长因子（VEGF）的释放。CCL 27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，该生物材料将 用适体官能化。适体的使用有望解决一个具有挑战性的矛盾， 高渗透性对于将氧气和药物有效输送到伤口床是必要的， 它限制了药物的持续释放。初步结果表明，高渗透性材料 用适体功能化的VEGF可以以持续的方式释放VEGF，用于加速伤口闭合。基于 根据这些令人信服的初步数据，拟议的研究旨在验证一个新的假设， 适体介导的VEGF和CCL 27的释放将促进伤口闭合和免疫稳态， 恢复皮肤的主要功能。具体目标包括1）半- 合成伤口敷料; 2）评价敷料调节免疫细胞的功能， 在组织、细胞和分子水平上促进伤口闭合;和3）评估修复的皮肤 有害的刺激。皮肤创伤是一个主要的公共卫生问题， 美国每年有100万人。该项目的成功将为创伤的治疗开辟一条新的途径 敷料，提高患者的生活质量，减轻皮肤沉重的社会经济负担 伤口