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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：
10460610
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/10460610
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 bioscaffold cell behavior cell motility chemokine design diabetic diabetic ulcer diabetic wound healing healing immune activation immunogenicity immunoregulation implantation improved in vivo limb amputation 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.

项目摘要在这项提案中，我们的目标是设计一种生物材料支架，通过改善糖尿病伤口愈合，我们发明了一种新的水凝胶生物材料子类，称为微孔退火颗粒凝胶或MAP凝胶。地图凝胶由使用微流体生成并原位组装的微观球形构建块组成，形成稳定的MAP支架。MAP支架已被证明通过促进皮肤和大脑的组织愈合来改善组织愈合。伤口炎症的孔隙度依赖性减少和促进细胞/组织整合。我们专注于材料改进，以应对糖尿病伤口材料治疗的三个已知困难：高免疫激活、增加的降解微环境和减少的新组织生成。我们特别我已经确定了三个MAP属性，我们可以独立地调节科学优化：孔隙几何形状（已知的免疫调节参数），降解性（过早的材料降解导致多孔性的损失），几何形状）和异质肝素“微岛”（我们开发的一种新材料策略，支架血管生成）。我们假设，单独调查和优化每个属性将加速糖尿病伤口闭合，最后，优化的性能可以协同组合。我们将使用以下表征工作流程来评估和优化每种材料特性：定量（性质依赖性），体外细胞应答（存活、增殖和迁移），体内免疫反应（通过FACS分析）、体内材料降解（通过组织学分析）和体内组织愈合/再生（免疫组织学分析）。我们的研究集中在糖尿病伤口环境，通过使用真皮细胞系，体外和糖尿病小鼠（db/db）夹板伤口愈合模型。我们方法的每一个目标都隔离了一个人材料属性，以简化调查。例如，使用单一水凝胶研究孔几何形状影响制剂和水凝胶制剂的影响使用单一孔几何形状（采用恒定的制剂和孔几何形状从我们成功的非糖尿病研究）。如果成功，该项目将提供更好地了解组织反应一种新的生物材料，并产生一种廉价和有效的支架治疗选择，伤口闭合