Chitosan/Gelatin Hydrogel Prolonged the Function of Insulinoma/Agarose Microspheres In Vivo During Xenogenic Transplantation K.-C. Yang, C.-C. Wu, Y.-H. Cheng, T.-F. Kuo, and F.-H. Lin ABSTRACT Purpose. A chitosan/gelatin solution with glycerol 2-phosphate disodium salt hydrate in liquid phase at room temperature becomes a hydrogel at 37°C. The material can be used as an injectable cell carrier into the human body for gelation in situ. We hoped that the chitosan/gelatin hydrogel provided extra protection for insulinoma/agarose microspheres during xenogenic transplantation. Materials and Methods. Mouse insulinoma was microencapsulated in agarose as microspheres, which were macroencapsulated in chitosan/gelatin hydrogel. Insulin secret- ing profiles were first demonstrated in vitro. Diabetic rats were injected subcutaneously with insulinoma/agarose microspheres or insulinoma/agarose microspheres suspended in chitosan/gelatin solution. The nonfasting blood glucose concentrations (NFBG) of diabetic rats were measured perioperatively. Rats were humanely killed 1 month postoperatively and the hydrogel was retrieved for histological examination. Results. The insulinoma/agarose microspheres continually secreted insulin for 1 month when macroencapsulated in chitosan/gelatin hydrogel in vitro. The NFBG of diabetic rats injected with insulinoma/agarose microspheres decreased to euglycemic status albeit hyperglycemia was restored within 10 days. The NFBG of diabetic rats injected with chitosan/gelatin hydrogel, which contained insulinoma/agarose microspheres, was main- tained at less than 200 mg/dL for 25 days. The histological section revealed immune cell infiltration and accumulation within the hydrogel and around the iusulinoma/agarose microspheres that may have contributed to the slowly increasing NFBG after day 25. Conclusion. This study showed that chitosan/gelatin hydrogel can be used as a cell carrier for an injectable bioartificial pancreas; the hydrogel prolonged the function of cells encapsulated in agarose microspheres during xenogenic transplantation. A LLOGENIC islet transplantation to compensate for pancreas dysfunction is an efficient therapy for type 1 diabetes, but the donor shortage restricts islet transplanta- tion as a major treatment. 1 Xenogenic species may be an alternative due to the sufficient donor supply. However, the obstacle of islet transplantation is immune rejection. The recipient must receive lifelong immunosuppressive therapy to overcome immune rejection. 2 Immunoisolation can facilitate the use of xenogenic cell sources to solve the problem of an insufficient donor supply, minimizing or eliminating the need for systemic immuno- suppression. 3 Microencapsulation is one type of immu- noisolation technique that has shown some encouraging outcomes in animal experiments. Microencapsulation can From the Institute of Biomedical Engineering (K.-C.Y., C.-C.W., Y.-H.C., T.-F.K., F.-H.L.), College of Medicine and College of Engineering, National Taiwan University, Taiwan; Department of Orthopedics (C.C.W.), En Chu Kong Hospital, Taipei, Taiwan; Institute of Veterinary Medicine (T.-F.K.), College of Biore- sources and Agriculture, National Taiwan University, Taipei, Taiwan; Division of Medical Engineering (F.-H.L.), National Health Research Institute, Miaoli, Taiwan. Address reprint requests to Dr. F.H. Lin, Institute of Biomed- ical Engineering, College of Medicine and College of Engineer- ing, National Taiwan University, No. 1, Jen Ai Rd., Sec. 1, Taipei, 10051, Taiwan. E-mail: double@ntu.edu.tw © 2008 by Elsevier Inc. All rights reserved. 0041-1345/08/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2008.06.092 Transplantation Proceedings, 40, 3623–3626 (2008) 3623