title: FTY720-loaded poly(DL-lactide-co-glycolide) electrospun scaffold significantly increases microvessel density over 7 days in streptozotocin-induced diabetic C57b16/J mice: preliminary results.
abstract: BACKGROUND
  Nanofiber scaffolds could improve islet transplant success by physically mimicking the shape of extracellular matrix and by acting as a drug-delivery vehicle. Scaffolds implanted in alternate transplant sites must be prevascularized or very quickly vascularized following transplantation to prevent hypoxia-induced islet necrosis. The local release of the S1P prodrug FTY720 induces diameter enlargement and increases in length density. The objective of this preliminary study was to evaluate length and diameter differences between diabetic and nondiabetic animals implanted with FTY720-containing electrospun scaffolds using intravital imaging of dorsal skinfold window chambers.
  
  
  METHODS
  Electrospun mats of randomly oriented fibers we created from polymer solutions of PLAGA (50:50 LA:GA) with and without FTY720 loaded at a ratio of 1:200 (FTY720:PLAGA by wt). The implanted fiber mats were 4 mm in diameter and ∼0.2 mm thick. Increases in length density and vessel diameter were assessed by automated analysis of images over 7 days in RAVE, a Matlab program.
  
  
  RESULTS
  Image analysis of repeated measures of microvessel metrics demonstrated a significant increase in the length density from day 0 to day 7 in the moderately diabetic animals of this preliminary study (P < .05). Furthermore, significant differences in length density at day 0 and day 3 were found between recently STZ-induced moderately diabetic and nondiabetic animals in response to FTY720 local release (P < .05, Student t test).
  
  
  CONCLUSIONS
  Driving the islet revascularization process using local release of factors, such as FTY720, from biodegradable polymers makes an attractive system for the improvement of islet transplant success. Preliminary study results suggest that a recently induced moderately diabetic state may potentiate the mechanism by which local release of FTY720 from polymer fibers increases length density of microvessels. Therefore, local release of S1P receptor-targeted drugs is under further investigation for improvement of transplanted islet function.
authors.affiliation: Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Bowers
authors.forename: P
authors.initials: P
authors.lastname: Chhabra
authors.forename: L
authors.initials: L
authors.lastname: Langman
authors.forename: E A
authors.initials: EA
authors.lastname: Botchwey
authors.forename: K L
authors.initials: KL
authors.lastname: Brayman
mesh_terms: D000818:Animals; D001331:Automation; D001672:Biocompatible Materials / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D000860:Hypoxia; D007091:Image Processing, Computer-Assisted; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels; D057139:Nanofibers / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011409:Propylene Glycols / Q000008:administration & dosage*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013311:Streptozocin / Q000737:chemistry; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D007166:Immunosuppressive Agents; D011108:Polymers; D011409:Propylene Glycols; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013311:Streptozocin; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine