The nanoporous PCL membranes were prepared via the combination of thermally- and nonsolvent-induced phase separations. For the phase separation process, nonsolvent has significant effect on pore formation and drug release rate. In nonsolvent-induced phase separation, a large amount of nonsolvent was added to casting solutions in order to improve pore connectivity within the membrane. The use of a Teflon plate for membrane casting can result in uniform nanoporous membranes and consistent lysozyme diffusion. Pore connectivity was improved significantly when coagulation bath temperature was lowered. By using a 5°C water coagulation bath in the wet-process precipitation, the average pore size reduced from 90 nm to 55 nm while increasing the casting solution
concentration from 15 wt% to 25 wt% PCL. Thus, by varying the polymer concentration of the casting solution, the lysozyme release rate can be manipulated with precise control. The potential application of nanoporous PCL membranes to achieve the preferable zero-order release rate is demonstrated in this dissertation.
Along with achieving the zero-order release rate, the nanoporous PCL membranes also provide immunoprotection for cell-based therapies/devices. Immunoisolation can be achieved by preventing Immunoglobulin G (IgG) from diffusing through the nanoporous PCL membranes. With appropriate pore size, the nanoporous PCL membranes can allow the diffusion of therapeutic agents (lysozyme) and block the diffusion of immune molecules (IgG). The application of the nanoporous PCL membranes to cell-based therapies/devices is also demonstrated in this dissertation.
Extensive fibrosis induced by the healing process can be detrimental to the long-term performance of implantable applications. The prevention of fibroblast adhesion to the nanoporous PCL membrane surface is crucial for constant and well controlled drug release. This study shows a novel method to modify the nanoporous PCL membrane surface with poly(ethylene glycol) (PEG) . To achieve this goal, oxygen plasma and PEG(400) monoacrylate were used to graft the PEG onto the membrane surface through covalent bonding. Initially, various plasma treatment conditions were investigated to optimize the PEG-grafting quality and to achieve minimum fibroblast adhesion. After the treatment, water contact angle measurements and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) spectra confirmed that PEG was successfully grafted onto the PCL membrane. X-ray photoelectron spectroscopy (XPS) revealed that different plasma powers and treatment times can change the surface composition of membranes. Cell adhesion and morphology studies indicate that either lower plasma power or shorter treatment time is able to significantly improve resistance to cell adhesion. With the use of appropriate plasma treatment conditions, the effects of grafting density and PEG chain length on reducing fibroblast adhesion were also investigated in this study. PEG-diacrylates were also investigated for their influence on fibroblast adhesion. For PEG-diacrylates, increasing molecular weight can lead to a higher resistance against cell adhesion. However, PEG-diacrylates were not as effective as PEG(400)-monoacrylate for providing the resistance to cell adhesion.