Biomaterials by design

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Materials used in healthcare and the devices based on these materials generate a biological response and control of that response dictates the successful use of the device. We will build on a suite of materials based on methacrylic acid (MAA) that has unique regenerative properties, notably, but not only, the capacity to regenerate blood vessels without any biological components. Such regenerative ability appears to be an intrinsic property of the material and the seemingly unique way it interacts with the host, once implanted. MAA based biomaterials generate vessel rich tissue (that integrates with the host) instead of a fibrous capsule that acts as a barrier. Using different co-monomers, the material is used as a coating for various medical devices (e.g., polypropylene mesh) to improve their biocompatibility or as an injectable gel that is initially liquid but gels in situ. Interestingly we also see increased nerve regeneration. The biological properties all appear to derive from the high negative charge associated with methacrylic acid. The focus here is on biomaterials development. Aim 1 is to combine the vascularizing activity of methacrylic acid with the ability of collagen to enable cell adhesion and migration, in the form of an injectable gel, that combines the vascularizing properties of MAA with the cell supportive character of collagen. Aim 2 is to develop an understanding of the physicochemical source of the biological activity of MAA by delineating the dynamics of the connection among material surface charge, the cell membrane potential. and the cell receptor distribution. MAA based materials appear to hyperpolarize cells (making the inside more negative than normal). Aim 3 is to design a material that engages with a cell receptor in a specific fashion. We ask whether materials can be designed to have a specific biological activity by starting with the protein structure of a receptor and through in silico analysis, identify small molecules that can be incorporated into novel polymers. The successful use of implantable medical devices (>$300 billion global industry; high growth rate; high potential for growth in Canada) is built on the biocompatibility of inert biomaterials such as silicone rubber and polypropylene, among other materials. But inert materials do not enable the next generation of medical devices because the normal foreign body response to the inert material is a barrier for some applications. Because it is biologically active without growth factors or cells, MAA is a novel biomaterial in this context. We seek to create novel forms of MAA, understand its mechanism of action and design yet others.