Development of Nanoporous Polyurethane Hydrogel Membranes for Cell Encapsulation

Abstract

Cell encapsulation for treatment of diseases like type 1 diabetes (T1D) has great potential when used in combination with development of insulin responsive beta cells. However, for translation of this therapy into clinical practice, there is a need for suitable encapsulation devices. Here, we report development of polyurethane-zwitterionic acrylate double network-based membranes for macro device-based cell encapsulation. Polyurethane hydrogels with 60 to 90% water content (WC) were evaluated for permeability and hydrogels with 80 and 90% WC were found to have highest permeability. Structural characterization of these hydrogels’ samples prepared cryogenically by scanning electron microscopy (cryo-SEM) revealed that 90% WC hydrogels were nanoporous with large interconnected pores. Tuning of porosity and structure was achieved by blending of hydrogels with varying WC resulting in pores of ~ 200 nm size. These membranes supported viability of encapsulated cells after removal of cytotoxic leachables by ethanol treatment. Double network formation was performed by UV polymerization and incorporation of zwitterionic groups was confirmed by ATR and WC of hydrogels. Varying of zwitterion type is allowed for tuning of WC of hydrogels. Gene expression of RAW 264.7 macrophages on exposure to the hydrogels found the zwitterionic double network hydrogels to be less stimulating than the bare hydrogel. To determine translational potential of the hydrogel, sterilization of the hydrogels using supercritical carbon dioxide was evaluated. Survivor enumeration testing revealed that the kill rate for the process ~ 1 log10 per 8 min and 2-h treatment is sufficient for sterility assurance level (SAL) of 10−6. Thus, we have developed hydrogel polyurethane membranes suitable for cell encapsulation in macro devices. We want to develop a device for cell encapsulation which is needed for treating diseases like T1D. In these devices, cells will be loaded and implanted in the body. These encapsulated cell secretions would provide the function of various endocrine organs. We have developed a hydrogel-based nanoporous membrane which would hold the cells and allow for exchange of nutrients and cell secretions. After the development of membrane, future studies will focus on evaluating the immune response to the hydrogel as well as long term delivery of immune modulatory drugs to prevent fibrosis. Various drug encapsulation and delivery designs will be evaluated for controlled localized delivery of the drugs. The optimum combination would then be combined with the hydrogels device and test their efficacy in regulating cell viability and immune response in animal models.