Engineering Injectable Microporous Hydrogels for Diabetic Wound Repair

用于糖尿病伤口修复的工程可注射微孔水凝胶

基本信息

批准号：
10297936
负责人：
Donald Richieri Griffin
金额：
$ 64.44万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-02 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10297936
关键词：
Address Affinity Amino Acid Substitution Animal Model Behavior Biocompatible Materials Blood Vessels Brain Caliber Cell Line Cells Chemicals Clinical Complication Crosslinker Defect Dermal Diabetic Foot Ulcer Diabetic mouse Engineering Ensure Environment Enzymes Exhibits Family suidae Foreign-Body Reaction Formulation Gel Generations Geometry Goals Hair follicle structure Heparin Heterogeneity Histology Hydrogels Immune response Immunofluorescence Immunologic In Situ In Vitro Individual Inflammation Inflammatory Injectable Instruction Intestines Investigation Island Lower Extremity Mechanics Mediating Microfluidics Microscopic Microspheres Muscle Natural regeneration Outcome Pathologic Patients Peptides Perfusion Pilot Projects Porosity Property Proteolysis Resistance Skin Skin wound healing Splint Device Structure Testing Thick Tissues Ulcer Vascularization Wound models angiogenesis articular cartilage base cell behavior cell motility chemokine design diabetic ulcer diabetic wound healing healing immune activation immunogenicity immunoregulation improved in vivo macrophage migration non-diabetic novel particle post stroke premature ratiometric regenerative response scaffold secondary outcome standard of care tissue regeneration wound wound closure wound environment wound healing wound treatment

项目摘要

PROJECT SUMMARY In this proposal, we aim to engineer a biomaterial scaffold to accelerate diabetic wound closure by improving upon a new sub-class of hydrogel biomaterials we have invented called Microporous Annealed Particle gel or MAP gel. MAP gels are composed of microscopic spherical building blocks made using microfluidic generation and assembled in situ to form a stable MAP scaffold. MAP scaffolds have been shown to improve tissue healing in both skin and brain through a porosity-dependent reduction in wound inflammation and promotion of cell/tissue integration. We are focusing on material improvements to counter three known difficulties for material-based treatment of diabetic wounds: abnormally high immune activation, increased degradative microenvironment, and diminished new tissue generation. Specifically, we have identified three MAP properties that we can independently modulate for scientific optimization: pore geometry (known immunomodulatory parameter), degradability (premature material degradation results in loss of porous geometry), and heterogeneous heparin “micro-islands” (a novel material strategy we have developed to improve intra- scaffold angiogenesis). We hypothesize that investigating and optimizing each property individually will accelerate diabetic wound closure and, finally, that the optimized properties can be combined synergistically. We will evaluate and optimize each material property using the following characterization workflow: in vitro property quantification (property-dependent), in vitro cell response (survival, proliferation, and migration), in vivo immune response (analysis by FACS), in vivo material degradation (analysis by histology), and in vivo tissue healing/regeneration (analysis by immunohistology). Our studies focus on the diabetic wound environment through use of dermal cell lines in vitro and a diabetic mouse (db/db) splinted wound healing model. Each Aim of our approach isolates an individual material property to simplify the investigation. For example, pore geometry impact is investigated using a single hydrogel formulation and hydrogel formulation impact uses a single pore geometry (constant formulation and pore geometry taken from our successful non-diabetic studies). If successful, this project will provide a better understanding of tissue response to a new class of biomaterial and produce an inexpensive and effective scaffold treatment option for accelerating diabetic wound closure.

项目摘要在此提案中，我们旨在设计生物材料支架，以通过改善A来加速糖尿病伤口。我们发明了称为微孔退火颗粒凝胶或MAP凝胶的新型水凝胶生物材料的子类。地图凝胶由使用微流体产生制成的微观球形构件组成，并原位组装形成稳定的地图支架。已显示MAP脚手架可以通过A改善皮肤和大脑的组织愈合孔隙率依赖性减少在细胞/组织整合的创新和促进中。我们专注于材料改进以抵消基于材料的糖尿病伤口的三个已知困难：异常高免疫激活，降解微环境增加并减少了新的组织产生。具体来说，我们已经确定了我们可以独立调节科学优化的三个地图属性：孔几何形状（已知的免疫调节参数），降解性（过早材料降解导致多孔的损失几何形状）和异质肝素“微岛”（我们已经开发出一种新的材料策略，旨在改善内部脚手架血管生成）。我们假设调查和优化每个物业将分别加速糖尿病伤口闭合，最后，可以协同组合优化的特性。我们将使用以下表征工作流来评估和优化每个材料属性：体外属性体外免疫的数量（依赖性），体外细胞反应（生存，增殖和迁移）反应（FACS分析），体内材料降解（组织学分析）和体内组织愈合/再生（通过免疫组织学分析）。我们的研究通过在体外和糖尿病小鼠（DB/dB）夹住伤口愈合模型。我们方法的每个目标都会隔离一个人材料财产以简化投资。例如，使用单个水凝胶研究了孔的几何影响配方和水凝胶配方冲击使用单个孔的几何形状（恒定配方和孔的几何形状根据我们成功的非糖尿病研究）。如果成功，该项目将更好地理解组织反应到一类新的生物材料，并产生一种廉价且有效的脚手架治疗选择，以加速糖尿病伤口闭合。