Engineering Adaptive Immune Responses from Hydrogel Scaffolds to Promote Tissue Regeneration

利用水凝胶支架设计适应性免疫反应以促进组织再生

基本信息

批准号：
10343752
负责人：
Joel H Collier
金额：
$ 63.94万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-02 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10343752
关键词：
Accidental Injury Adaptive Immune System Age American Amino Acids Antibodies Antibody Formation Antigens B-Lymphocytes Biocompatible Materials Biological Biological Assay CD3 Antigens CD4 Positive T Lymphocytes CD8B1 gene Cells Chemicals Cicatrix Crosslinker Deposition Diabetes Mellitus Disease Engineering Extracellular Matrix Fibrosis Flow Cytometry Goals Grant Growth Factor Hair follicle structure Health Care Costs Healthcare Systems Helper-Inducer T-Lymphocyte Hydrogels ITGAM gene IgG1 Immune response Immune signaling Immune system Immunity Immunohistochemistry Implant In Situ Infiltration Inflammation Innate Immune Response Innate Immune System Investigation Knockout Mice Lead Link Mediating Modification Mus Natural regeneration Operative Surgical Procedures Patients Peptides Phenotype Population Porosity Process Production Reporting Reverse Transcriptase Polymerase Chain Reaction Role Schedule Sebaceous Glands Signal Transduction Skin Skin Tissue Spleen Stains Structure Sweat Glands T-Lymphocyte Tensile Strength Testing Time Tissues Triage Tumor stage adaptive immune response base biomaterial compatibility bioscaffold capsule cost crosslink draining lymph node enantiomer functional loss healing hydrogel scaffold immune activation implant material implantation improved macrophage particle peptide L prevent recruit regenerative regenerative repair repaired response restoration scaffold skin regeneration stem cell growth stem cell therapy subcutaneous success tissue regeneration tissue repair tissue support frame wound wound closure wound healing wound treatment

项目摘要

Summary Biomaterial scaffolds represent a promising approach for material-based tissue regeneration. We previously developed microporous annealed particle (MAP) hydrogels - a flowable, microparticle-based hydrogel in which neighboring hydrogel particles are linked in situ to form a porous scaffold that accelerates wound healing. Recently, we found that a relatively simple modification to the crosslinker peptide from L-enantiomer to D- enantiomer resulted in substantial skin regeneration and that this regeneration only occurs when the adaptive immune system is intact. Further investigation revealed that although D-chiral peptides were poor activators of macrophage innate immune signaling, D-chiral peptides within MAP (D-MAP) elicited significant antigen-specific immunity. In this proposal, we will further investigate the ability of our D-MAP material to activate the adaptive immune system and lead to skin tissue regeneration. Aim 1 will focus on further understanding any role of the innate immune system and the ability of MAP scaffold microstructure to dictate macrophage phenotype. Aim 2 will focus on testing our hypothesis that the adaptive immune system is activated by our material and leads to regenerative wound healing. Aim 3 will investigate other biomaterial approaches to present D-peptides and further control immune system activation.

概括生物材料支架代表了一种基于材料的组织再生的有前途的方法。我们以前开发的微孔退火颗粒（MAP）水凝胶 - 一种可流动的，基于微粒的水凝胶，其中相邻的水凝胶颗粒原位连接起来，形成一个多孔脚手架，可加速伤口愈合。最近，我们发现从l-偏南剂到d-的交联肽进行了相对简单的修饰。对映异构体导致了大量的皮肤再生，并且这种再生仅在适应性时才发生免疫系统完好无损。进一步的研究表明，尽管D-毒性肽是较差的活化剂巨噬细胞先天免疫信号传导，MAP（D-MAP）内的D-手续肽引起了显着的抗原特异性免疫。在此提案中，我们将进一步研究D-MAP材料激活适应性的能力免疫系统并导致皮肤组织再生。 AIM 1将专注于进一步了解先天免疫系统以及地图支架微观结构决定巨噬细胞表型的能力。目标2 将专注于测试我们的假设，即自适应免疫系统被我们的材料激活，并导致再生伤口愈合。 AIM 3将研究其他生物材料的方法来介绍D肽和进一步控制免疫系统激活。