Chitosan/gelatin hydrogel prolonged the function of insulinoma/agarose microspheres in vivo during xenogenic transplantation.
OBJECTIVE
A chitosan/gelatin solution with glycerol 2-phosphate disodium salt hydrate in liquid phase at room temperature becomes a hydrogel at 37 degrees 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.


METHODS
Mouse insulinoma was microencapsulated in agarose as microspheres, which were macroencapsulated in chitosan/gelatin hydrogel. Insulin secreting 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 maintained 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.


CONCLUSIONS
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.
Yang
K-C
KC
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taiwan.
Wu
C-C
CC
Cheng
Y-H
YH
Kuo
T-F
TF
Lin
F-H
FH
D000818:Animals; D048271:Chitosan / Q000627:therapeutic use; D005780:Gelatin / Q000627:therapeutic use*; D020100:Hydrogels / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D051379:Mice; D009368:Neoplasm Transplantation / Q000379:methods* / Q000473:pathology; D051381:Rats; D012685:Sepharose; D014183:Transplantation, Heterologous
D020100:Hydrogels; D007328:Insulin; D005780:Gelatin; D012685:Sepharose; D048271:Chitosan