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

• 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
• 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

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.

总结 生物材料支架是一种很有前途的基于材料的组织再生方法。我们之前 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以形成加速伤口愈合的多孔支架。 最近，我们发现，将交联肽从L-对映异构体修饰为D-对映异构体的相对简单的修饰， 对映异构体导致大量的皮肤再生，这种再生只发生在适应性 免疫系统完好无损进一步的研究表明，虽然D-手性肽是差的激活剂， 在巨噬细胞天然免疫信号转导中，MAP内的D-手性肽（D-MAP）引起显著的抗原特异性 免疫力在这个提议中，我们将进一步研究我们的D-MAP材料激活自适应的能力。 免疫系统和导致皮肤组织再生。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。目的2 将专注于测试我们的假设，即适应性免疫系统被我们的材料激活，并导致 再生伤口愈合目的3将研究其他生物材料的方法来呈现D-肽， 进一步控制免疫系统的激活。