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：
10571804
负责人：
Joel H Collier
金额：
$ 63.3万
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/10571804
关键词：
Acceleration 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 Injury Innate Immune Response Innate Immune System Investigation Knockout Mice Link Macrophage Mediating Modification Mus Muscle 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 adaptive immune response biomaterial compatibility bioscaffold bone capsule cost crosslink draining lymph node enantiomer functional loss healing hydrogel scaffold immune activation immunoregulation implant material implantation improved particle peptide L prevent recruit regenerative regenerative repair repaired response restoration scaffold skin regeneration stem cell therapy stem cells subcutaneous success tissue regeneration tissue repair 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基于材料的组织再生的一种有前途的方法。我们之前开发了微孔退火颗粒（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形成多孔支架，加速伤口愈合。最近，我们发现交联肽从 L-对映体到 D-对映体的相对简单的修饰对映异构体导致大量皮肤再生，并且这种再生仅在适应性免疫系统完好无损。进一步的研究表明，虽然 D-手性肽是较差的激活剂巨噬细胞先天免疫信号，MAP 内的 D-手性肽 (D-MAP) 引发显着的抗原特异性免疫。在本提案中，我们将进一步研究 D-MAP 材料激活自适应能力的能力免疫系统并导致皮肤组织再生。目标 1 将侧重于进一步了解先天免疫系统和 MAP 支架微结构决定巨噬细胞表型的能力。目标2 将重点测试我们的假设，即适应性免疫系统被我们的材料激活并导致伤口再生愈合。目标 3 将研究其他生物材料方法来呈现 D 肽和进一步控制免疫系统的激活。