There is significant need for effective medical adhesives that function reliably on wet tissue surfaces with minimal inflammatory insult. To address these performance characteristics, we have generated a synthetic adhesive biomaterial inspired by the protein glues of marine mussels. In-vivo performance was interrogated in a murine model of extrahepatic syngeneic islet transplantation, as an alternative to standard portal administration. The adhesive precursor polymer consisted of a branched poly(ethylene glycol) (PEG) core, whose endgroups were derivatized with catechol, a functional group abundant in mussel adhesive proteins. Under oxidizing conditions, adhesive hydrogels formed in less than one minute from catechol-derivatized PEG (cPEG) solutions. Upon implantation, the cPEG adhesive elicited minimal acute or chronic inflammatory response in C57BL6 mice, and maintained an intact interface with supporting tissue for up to one year. In-situ cPEG adhesive formation was shown to efficiently immobilize transplanted islets at the epididymal fat pad and external liver surfaces, permitting normoglycemic recovery and graft revascularization. These findings establish the use of synthetic, biologically-inspired adhesives for islet transplantation at extrahepatic sites.

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Background Quantification of islet mass is a crucial criterion for defining the quality of the islet product ensuring a potent islet transplant when used as a therapeutic intervention for select patients with type I diabetes. Methods This multi-center study involved all 8 member institutions of the National Institutes of Health-supported Islet Cell Resources (ICR) consortium. The study was designed to validate the standard counting procedure for quantifying isolated, dithizone-stained human islets as a reliable methodology by ascertaining the accuracy, repeatability (intra-observer variability), and intermediate precision (inter-observer variability). The secondary aim of the study was to evaluate a new software-assisted digital image analysis method as a supplement for islet quantification. Results The study demonstrated the accuracy, repeatability and intermediate precision of the standard counting procedure for isolated human islets. This study also demonstrated that software-assisted digital image analysis as a supplemental method for islet quantification was more accurate and consistent than the standard manual counting method. Conclusions Standard counting procedures for enumerating isolated stained human islets is a valid methodology, but computer-assisted digital image analysis assessment of islet mass has the added benefit of providing a permanent record of the isolated islet product being evaluated that improves quality assurance operations of current good manufacturing practice (cGMP).

Arterialization of the portal vein is being propagated as a technical possibility in liver transplant recipients with pre‐existing portal vein thrombosis. In our own small sries, portal vein arterialization (PVA) was carried out in four patients undergoing orthotopic liver transplantation. In three of these cases, the portal vein was anastomosed to the aorta via an interposed iliac artery, and in one case, directly to the hepatic artery. After PVA, all transplants showed regular initial function. Two patients died postoperatively afer 19 and 50 days, of intra‐abdominal haemorrhage and liver necrosis with thrombosis of the portal vein, respectively. A further patient had previously developed fibrosis of the liver, which led to the death of the patient 11 months after PVA. In the remaining patient, chronic rejection requiring re‐transplantation developed 24 months after PVA had been performed. These unfavourable results prompt the conclusion that PVA cannot be recommended as a stndard clinical procedure.

The epididymal fat pad was evaluated as a site of islet transplantation in a syngeneic murine model of diabetes by comparing the transplant outcomes to that of islets transplanted intraportal. Mouse islets engrafted on the intra-abdominal epididymal fat pad ameliorated streptozotocin-induced hyperglycemia with similar efficacy as grafts implanted intraportally. Mice that received as few as 50 islets, either intraportal or in the epididymal fat pad, displayed similar glucose tolerance curves. Bioluminescence imaging and glucose measurement showed stable luminescence signals and blood glucose levels for over 5 months in both transplant sites using transgenic luciferase-positive islets. Prompt recurrent hyperglycemia occurred in all mice after removal of the epididymal fat pad bearing the islet graft. Histological examination of the grafts showed well-granulated insulin containing cells surrounded by healthy adipocytes. This study indicates that the epididymal fat pad maybe a useful islet transplant site in the mouse model for effective glycemic control.