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.

Medical implants will benefit from materials with inherent ability to promote angiogenesis and reduce oxidative stress associated with inflammation caused by the surgery and the presence of a foreign body. We will invent a series of biodegradable metallo-elastomers that can mimic the activity of metalloenzymes to achieve angiogenesis and anti-inflammation.