Evaluation of 3D bioprinted pancreatic islets for insulin secretion in diabetic rats

3D printing of biomaterials entrapped with functional cells has emerged as a promising technique for cell-based therapy. Development of biomaterial composite that enables 3D bioprinting while providing structural support and nutrient diffusion for cell survival and function is a challenge. In this study, pancreatic cell-seeded scaffolds were 3D bioprinted using composites made of sodium alginate, sodium hyaluronate, and polyethylene glycol diacrylate to provide biocompatibility, mechanical strength, and structural stability. The beta cell population within the pancreatic cells isolated from Sprague Dawley rats was found to be 66 ± 12%. The cell suspension was evaluated for glucose-stimulated insulin secretion (GSIS), where incubation with 22.2 mmol/L glucose resulted in the production of 1272 ± 113 µIU/mL and 405 ± 115 µIU/mL insulin into the cell pellet and cell supernatant, respectively. The two photon confocal microscope showed that rhodamine B uptake into the 3D printed cell scaffold significantly (P < 0.05) increased with time. The cell viability (MTT) assay showed pancreatic cell viability of 68.2 ± 3.8%, and 69.2 ± 6.2% after 21 and 28 days, respectively. The live dead assay showed pancreatic cell viability of 51.5 ± 11.9%, and 47.4 ± 3.8% after 21 and 28 days, respectively. The cell-entrapped scaffolds were implanted subcutaneously in diabetic Sprague-Dawley rats. The rats showed a significant (P < 0.05) increase in the insulin levels and a significant (P < 0.05) reduction in the plasma glucose levels when compared to sham control. The implant was recovered on day 28 and found no signs of infection and capsule formation at the site of implantation. Histological examination revealed no signs of foreign body response, indicating that the implant was biocompatible. Taken together, 3D printed biocomposite material with pancreatic cells can be developed for long-acting diabetes control.