Functional Polymers and Capsules

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My research involves the development of reactive, multi-responsive polymers and their use in a biomaterials context, including therapeutic cell encapsulation and in cell research. A major focus is on preparing pairs of water-soluble polymers that spontaneously react with each other to form cell-compatible hydrogels. Some of these polymers have cationic and anionic charges that allow them to be coated onto cell-containing calcium alginate capsules, where electrostatic attraction enhances their covalent cross-coupling. The resulting, covalently reinforced cell-containing capsules, are designed for long-term transplantation into, e.g., peritoneal cavities of patients suffering from hormone deficiency disorders such as insulin-dependant Diabetes. These capsules need to balance four requirements: 1. be permeable enough to allow nutrient and insulin diffusion, 2. provide a physical barrier to protect the encapsulated cells from the hosts' immune system, 3. be non-inflammatory themselves, and 4. resist degradation for one year. Current state-of-the-art capsules are largely based on polycation-coated calcium alginate, derived from seaweed, that elicit inflammatory and immune responses due to the polycation, as well as biocontaminants and inflammatory motifs in the alginate. We were able to demonstrate that crosslinked synthetic hydrogel coatings can reduce the hosts' immune response, attributed to both physical shielding of the alginate, and to the strongly hydrophilic nature of these hydrogel coatings due to the presence of excess carboxylate anions. ***We have since generated a suite of reactive polymers based on polyelectrolytes and polyampholytes with inherently anti-fouling properties. Some of these polymers can form liquid coacervates under physiological conditions, which should enable new modes of deposition onto cell-containing capsules: we will explore depositing liquid coacervates onto calcium alginate capsules, followed by in-situ crosslinking, to form unique micron-range crosslinked shells that may cover the small but critical fraction of cells always protruding from alginate capsules. Some of these polyampholytes have promise as non-cytotoxic cryoprotectants for low temperature storage of stem cells and red blood cells. We further have identified synthetic polymers that may replace alginate in the cell-containing hydrogel core, and will test if they are amenable to crosslinked overcoating, or indeed can be made to spontaneously crosslink once in capsule form. In addition, we have developed giant (10 - 40 micron) monodisperse hydrogel beads formed by precipitation polymerization, that have potential as cell mimics or supports in 3D cell cultures. Our work ranges from fundamental polymer research, to collaboration with stem cell researchers and diabetes researcher/clinicians, aiming to bring synthetic polymers to bear on growing biomedical needs.**