Intramedullary Cavity as an Implant Site for Bioartificial Pancreas: An In Vivo Study on Diabetic Canine

Abstract

Fibrous tissue outgrowth and hypoxia are the major restrictions for the application of bioartificial pancreas (BAP). Accordingly, the intramedullary cavity is proposed as an implant site, and a BAP constructed of calcium phosphate cement chamber was implanted. Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a calcium phosphate cement chamber to fabricate a BAP. BAPs were implanted in the femoral intramedullary cavity of diabetic dogs. Pre- and postprandial blood glucose levels were monitored perioperatively. Blood samples were collected for the analysis of C-peptide level, and physiological conditions were observed at predetermined intervals. BAPs were retrieved at 12 weeks postoperatively for histologic examination. Preprandial blood glucose level of diabetic dogs decreased from 420 ± 25 to 223 ± 47 mg/dL at 1 day postoperatively and was maintained in the range of 259 ± 36 mg/dL for 12 weeks. As serum C-peptide level increased from 5.3 ± 2.8 to 105.7 ± 19.4 pmol/L, the rate of decrease of postprandial blood glucose was accelerated. Histologic examination revealed that recipient bone tissues were binding to the surfaces of BAPs directly; there was no development of fibrous tissue. Immunohistochemical stain was positive for insulin in the enclosed insulinoma cells. This study demonstrated that BAPs implanted into the intramedullary cavity functioned well during the experimental period. Thus, the intramedullary cavity can serve as an implant site for BAPs.