PEG Hydrogel-Nanogel Composite Scaffolds as Extracellular Matrix Platforms
Tugba Bal1, Yoshihide Hashimoto2, Yoshihiro Sasaki2, Kazunari Akiyoshi2, Seda Kizilel1
1Koc University, Chemical and Biological Engineering, Istanbul 34450, Turkey
2Kyoto University, Department of Polymer Chemistry, Kyoto 615-8510, Japan
Design of semi-permeable membranes is promising to protect transplanted pancreatic islets from immune attack for an immunosuppressant-free clinical treatment of type 1 diabetes. However, lack of an extracellular mimic limits the potential of such systems. Ligand presentation in 3D crosslinked scaffolds plays a pivotal role for cell fate after transplantation. In this study, we investigated the potential of incorporating nanoparticles with sugar and cholesterol groups on pancreatic islet function. Nanogels synthesized with acrylated cholesterol bearing pullulan (CHPOA) were crosslinked with PEG hydrogels, and encapsulation of pancreatic islets within this composite was carried out to characterize glucose stimulated insulin secretion function. Incorporation of CHPOA nanogels into PEG hydrogels did not alter swelling and porosity properties of ligand functionalized PEG hydrogels. ATP content measurements as an indicator of cell survival in composite hydrogels demonstrated the potential of this composite scaffold for improved viability of MIN6 pseudoislets. Challenging of hydrogel coated MIN6 cell clusters provided control over the level of insulin secretion. Further, subcutaneous implantation of this hydrogel composite in a diabetic mouse model confirmed minimal inflammation at the implantation site. The results presented here are encouraging to address the limitations associated with donor source and long term islet function for clinical treatment of diabetes.