title: In vivo vascularization of anisotropic channeled porous polylactide-based capsules for islet transplantation: the effects of scaffold architecture and implantation site.
abstract: The replacement of pancreatic islets for the possible treatment of type 1 diabetes is limited by the extremely high oxygen demand of the islets. To this end, here we hypothesize to create a novel extra-hepatic highly-vascularized bioartificial cavity using a porous scaffold as a template and using the host body as a living bioreactor for subsequent islet transplantation. Polylactide-based capsular-shaped anisotropic channeled porous scaffolds were prepared by following the unidirectional thermally-induced phase separation technique, and were implanted under the skin and in the greater omentum of Brown Norway rats. Polyamide mesh-based isotropic regular porous capsules were used as the controls. After 4weeks, the implants were excised and analyzed by histology. The hematoxylin and eosin, as well as Masson's trichrome staining, revealed a) low or no infiltration of giant inflammatory cells in the implant, b) minor but insignificant fibrosis around the implant, c) guided infiltration of host cells in the test capsule in contrast to random cell infiltration in the control capsule, and d) relatively superior cell infiltration in the capsules implanted in the greater omentum than in the capsules implanted under the skin. Furthermore, the anti-CD31 immunohistochemistry staining revealed numerous vessels at the implant site, but mostly on the external surface of the capsules. Taken together, the current study, the first of its kind, is a significant step-forward towards engineering a bioartificial microenvironment for the transplantation of islets.
authors.affiliation: Department of Biomaterials and Bioanalogous Polymer Systems, Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic. kasoju@imc.cas.cz and kubies@imc.cas.cz; Department of Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. jkri@ikem.cz.
authors.forename: N
authors.initials: N
authors.lastname: Kasoju
authors.forename: D
authors.initials: D
authors.lastname: Kubies
authors.forename: E
authors.initials: E
authors.lastname: Fábryová
authors.forename: J
authors.initials: J
authors.lastname: Kříž
authors.forename: M M
authors.initials: MM
authors.lastname: Kumorek
authors.forename: E
authors.initials: E
authors.lastname: Sticová
authors.forename: F
authors.initials: F
authors.lastname: Rypáček
mesh_terms: D000818:Animals; D016880:Anisotropy; D002214:Capsules; D060833:Cellular Microenvironment; D005355:Fibrosis; D007515:Islets of Langerhans; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D051381:Rats; D011914:Rats, Inbred BN; D054457:Tissue Scaffolds
chemical_list: D002214:Capsules; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid