Biodegradable metallo-elastomer

可生物降解的金属弹性体

• 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
• 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

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.

可生物降解的金属弹性体 可生物降解的弹性体可用于许多生物医学应用。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构成。前者 生产热固性材料，通常具有高弹性，但交联后无法加工。后者 生产热塑性塑料，其弹性通常较低，但更易于加工。金属配位键 具有介于共价键和弱物理键之间的中等键强度。我们将发明一系列 可生物降解的金属弹性体，其中交联由金属配位键形成。一个优点是 这种方法是一种聚合物配体可以结合许多不同的金属离子，从而产生变体 弹性体，每种都具有独特的性能。此外，金属离子具有固有的生物活性， 生物材料方面尚未得到充分探索。我们的初步研究表明，该材料可以具有高弹性； 匹配或超过通过共价键交联的弹性体的弹性。此外，由此产生的 弹性体含有极少量的金属离子，并且没有明显的毒性。相反，他们是 比用于许多 FDA 批准的医疗植入物的聚己内酯 (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。酶通过以下方式进一步增强和指定这些活性： 提供氨基酸配体和结合口袋。铜离子（Cu2+）是最早的血管生成因子之一 发现并已知可上调血管生成生长因子。在氧化还原酶如超氧化物中 歧化酶 Cu2+ 提供了分解超氧自由基的关键氧化还原活性。这项研究将 阐明金属弹性体的结构与功能关系有两个具体目标：第一个目标是探索 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，我们将在皮肤伤口愈合模型中测试本提案中创建的聚合物。 目标 1 将研究铜金属弹性体的血管生成特性及其在改善血管生成方面的潜力。 皮瓣的存活。目标2将研究铜金属弹性体分解活性氧的能力 使用与超氧化物歧化酶活性位点基本相似的聚合物的物种。这些材料 可能会增加皮肤移植的整合。 该项目完成后，我们希望建立一个关于金属弹性体如何相互作用的基本框架 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，我们将欣赏这些弹性体在提高生存率和 植皮和皮瓣的整合。所获得的知识将从根本上影响生物材料的设计和 实际上影响医疗植入物的宿主整合。