Biodegradable metallo-elastomer

可生物降解的金属弹性体

基本信息

批准号：
10687179
负责人：
Yadong Wang
金额：
$ 37.64万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10687179
关键词：
Active Sites Amino Acids Angiogenic Factor Antiinflammatory Effect Apligraf Area Beds Benchmarking Binding Biocompatible Materials Blood Vessels Clinical Collagen Copper Dose Effectiveness Elasticity Elastomers Endothelium Engineered skin Engineering Enzymes Equilibrium Exhibits Extracellular Matrix FDA approved Family Fibrosis Foreign Bodies Formulation Gel Graft Survival Growth Factor Histidine Implant In Vitro Inflammation Ions Knowledge Ligands Metals Modeling Mus Operative Surgical Procedures Oxidation-Reduction Oxidative Stress Polymers Pre-Clinical Model Process Property Proteins Reactive Oxygen Species Research Schiff Bases Series Skin Skin graft Skin wound healing Specific qualifier value Structure Structure-Activity Relationship Subgroup Superoxide Dismutase Superoxides Testing Tissues Toxic effect Transition Elements Tube Variant Vascular Endothelial Growth Factors Vertebral column angiogenesis biological systems biomaterial compatibility covalent bond crosslink density design elastomeric first-in-human healing improved in vivo invention medical implant metalloenzyme mimetics novel polycaprolactone research clinical testing response soft tissue success tissue regeneration tissue repair validation studies

Active Sites Amino Acids Angiogenic Factor Antiinflammatory Effect Apligraf Area Beds Benchmarking Binding Biocompatible Materials Blood Vessels Clinical Collagen Copper Dose Effectiveness Elasticity Elastomers Endothelium Engineered skin Engineering Enzymes Equilibrium Exhibits Extracellular Matrix FDA approved Family Fibrosis Foreign Bodies Formulation Gel Graft Survival Growth Factor Histidine Implant In Vitro Inflammation Ions Knowledge Ligands Metals Modeling Mus Operative Surgical Procedures Oxidation-Reduction Oxidative Stress Polymers Pre-Clinical Model Process Property Proteins Reactive Oxygen Species Research Schiff Bases Series Skin Skin graft Skin wound healing Specific qualifier value Structure Structure-Activity Relationship Subgroup Superoxide Dismutase Superoxides Testing Tissues Toxic effect Transition Elements Tube Variant Vascular Endothelial Growth Factors Vertebral column angiogenesis biological systems biomaterial compatibility covalent bond crosslink density design elastomeric first-in-human healing improved in vivo invention medical implant metalloenzyme mimetics novel polycaprolactone research clinical testing response soft tissue success tissue regeneration tissue repair validation studies

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项目摘要

Biodegradable metallo-elastomer Biodegradable elastomers are useful in many biomedical applications. Elastomers are crosslinked network polymers. The crosslinks can be made of covalent bonds or weak bonds such as a physical bond. The former produces thermosets, which usually have high elasticity but cannot be processed after crosslinking. The latter produces thermoplastics, which usually have lower elasticity but are easier to process. Metal coordination bond has medium bond strength in between covalent bonds and weak physical bonds. We will invent a series of biodegradable metallo-elastomers where the crosslink is formed by metal coordination bonds. An advantage of this approach is that one polymeric ligand can bind many different metal ions, thereby producing variant elastomers, each with unique properties. Furthermore, metal ions have inherent bioactivities, an area underexplored in biomaterials. Our preliminary study demonstrates that the materials can be highly elastic; matching or exceeding the elasticity of elastomers crosslinked by covalent bonds. Furthermore, the resultant elastomers contain very small amounts of metal ions and exhibit no noticeable toxicity. On the contrary, they are more biocompatible than polycaprolactone (PCL), used in many FDA-approved medical implants. Many transition metal ions have inherent bioactivity. Enzymes further enhance and specify these activities by providing amino acid ligands and binding pockets. Copper ion (Cu2+) is one of the first angiogenic factors discovered and is known to upregulate angiogenic growth factors. In redox enzymes such as superoxide dismutase, Cu2+ provides the critical redox activity to break down the superoxide radical. This research will elucidate the structure-function relationship of metallo-elastomers in two specific aims: the first will explore the pro-angiogenic properties of Cu2+, the second will study the anti-ROS activities of Cu2+. Taking advantage of the elasticity of these polymers, we will test the polymers created in this proposal in models of skin wound healing. Aim 1 will investigate the angiogenic properties of Cu metallo-elastomers and their potential in improving the survival of skin flaps. Aim 2 will investigate the capability of Cu metallo-elastomer to decompose reactive oxygen species using a polymer bearing basic resemblance to the active site of superoxide dismutase. These materials will potentially increase the integration of skin grafts. Upon completion of this project, we expect to have built a basic framework on how metallo-elastomers interact with biological systems. We will better understand how altering the basic structure of the elastomer will impact its function. Furthermore, we will appreciate the effectiveness of these elastomers in increasing the survival and integration of skin grafts and skin flaps. The knowledge gained will fundamentally impact biomaterial design and practically impact host integration of medical implants.

可生物降解的金属启动器可生物降解的弹性体在许多生物医学应用中都有用。弹性体是交联网络聚合物。交联可以由共价键或弱键（例如物理键）组成。前者产生的热固体通常具有较高的弹性，但在交联后不能处理。后者产生热塑性，通常具有较低的弹性，但更易于处理。金属协调键在共价键和弱物理键之间具有中等键强度。我们将发明一系列可生物降解的金属弹性体，其中交叉链接是由金属配位键形成的。一个优势这种方法是一种聚合配体可以结合许多不同的金属离子，从而产生变体弹性体，每个弹性体具有独特的属性。此外，金属离子具有固有的生物活性，一个区域在生物材料中毫无疑问。我们的初步研究表明，材料可以高度弹性。通过共价键交联的弹性体的匹配或超过弹性。此外，结果弹性体含有少量的金属离子，并且没有明显的毒性。相反，他们是在许多FDA批准的医疗植入物中使用的比多丙酮酸（PCL）更具生物相容性。许多过渡金属离子具有固有的生物活性。酶进一步增强并通过提供氨基酸配体和结合口袋。铜离子（Cu2+）是第一个血管生成因子之一发现并已知可以上调血管生成因子。在氧化还原酶（例如超氧化物）中歧化酶Cu2+提供了关键的氧化还原活性，以分解超氧化物自由基。这项研究会在两个具体目的中阐明金属弹性物的结构功能关系：第一个将探索 Cu2+的促血管生成特性，第二个将研究Cu2+的抗ROS活性。利用这些聚合物的弹性，我们将测试该建议在皮肤伤口愈合模型中产生的聚合物。 AIM 1将研究Cu金属弹性体的血管生成特性及其在改善的潜力皮瓣的生存。 AIM 2将研究Cu金属启动器分解活性氧的能力使用与超氧化物歧化酶活性位点具有基本相似度的聚合物的物种。这些材料可能会增加皮肤移植物的整合。该项目完成后，我们希望已经建立了一个基本框架与生物系统。我们将更好地了解改变弹性体的基本结构将如何影响它的功能。此外，我们将感谢这些弹性体在增加生存和皮肤移植物和皮瓣的整合。获得的知识将从根本上影响生物材料设计，并实际上会影响医疗植入物的宿主整合。