Biodegradable metallo-elastomer

可生物降解的金属弹性体

• 批准号: 10522678
• 负责人: Yadong Wang
• 金额: $ 35.41万
• 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/10522678
• 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; Ligand Binding; 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; Surgical Flaps; 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; 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metallo-elastomer