title: The Efficacy of a Prevascularized, Retrievable Poly(D,L,-lactide-co-ε-caprolactone) Subcutaneous Scaffold as Transplantation Site for Pancreatic Islets.
abstract: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally, this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here, we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) scaffold.
  
  
  
  Three dosages of rat islets, that is, 400, 800, and 1200, were implanted in immune compromised mice to test the efficacy (n = 5). Islet transplantation under the kidney capsule served as control (n = 5). The efficacy was determined by nonfasting blood glucose measurements and glucose tolerance tests.
  
  
  
  Transplantation of 800 (n = 5) and 1200 islets (n = 5) into the scaffold reversed diabetes in respectively 80 and 100% of the mice within 6.8 to 18.5 days posttransplant. The marginal dose of 400 islets (n = 5) induced normoglycemia in 20%. The glucose tolerance test showed major improvement of the glucose clearance in the scaffold groups compared to diabetic controls. However, the kidney capsule was slightly more efficacious because all 800 (n = 5) and 1200 islets (n = 5) recipients and 40% of the 400 islets (n = 5) recipients became normoglycemic within 8 days. Removal of the scaffolds or kidney grafts resulted in immediate return to hyperglycemia. Normoglycemia was not achieved with 1200 islets in the unmodified skin group.
  
  
  
  Our findings demonstrate that the prevascularized poly (D,L-lactide-co-ε-caprolactone) scaffold maintains viability and function of islets in the subcutaneous site.
authors.affiliation: 1 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2 Department of Surgery, University of California Irvine, Orange, CA. 3 Polyganics, Groningen, The Netherlands. 4 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 5 Department of Developmental BioEngineering, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands. 6 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. 7 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 8 Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 9 Department of Biomedical Engineering, University of California Irvine, Irvine, CA. 10 Department of Surgery, University of California Irvine, Orange, CA. 11 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Smink
authors.forename: Shiri
authors.initials: S
authors.lastname: Li
authors.forename: Don T
authors.initials: DT
authors.lastname: Hertsig
authors.forename: Bart J
authors.initials: BJ
authors.lastname: de Haan
authors.forename: Leendert
authors.initials: L
authors.lastname: Schwab
authors.forename: Aart A
authors.initials: AA
authors.lastname: van Apeldoorn
authors.forename: Eelco
authors.initials: E
authors.lastname: de Koning
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Faas
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
authors.forename: Paul
authors.initials: P
authors.lastname: de Vos
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000175:diagnosis / Q000601:surgery*; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D007515:Islets of Langerhans / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D008819:Mice, Nude; D011091:Polyesters / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D040521:Subcutaneous Tissue / Q000098:blood supply* / Q000601:surgery*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D011091:Polyesters; C062968:lactide-caprolactone copolymer