title: Controlled heparin conjugation on electrospun poly(ε-caprolactone)/gelatin fibers for morphology-dependent protein delivery and enhanced cellular affinity.
abstract: Electrospun fibrous scaffolds have now been shown to possess great potential for tissue engineering applications, owing to their unique mimicry of natural extracellular matrix structure. In this study, poly(ε-caprolactone) and gelatin were electrospun to fabricate tissue-engineered scaffolds with three different fiber morphologies (1.0 μm, 3.0 μm and co-electrospun containing both 1.0 and 3.0 μm diameter fibers). Subsequently, these scaffolds were conjugated with heparin to immobilize a bioactive molecule by electrostatic interactions. This study determined the quantity of heparin conjugation on the scaffolds and that the crosslinking time and the fiber morphologies govern the extent of heparin conjugation on the fibers. In order to evaluate the release capacity of the heparin-conjugated scaffolds, lysozyme was used as a model protein for conjugation. The heparin-conjugated scaffolds provided high loading efficiency and cumulative release of lysozyme with a relatively linear relationship. In addition, the release kinetics was significantly dependent on heparin conjugation and fiber morphology. This fundamental investigation into how fiber morphology and crosslinking protocols can affect the heparin binding ability of electrospun fibers is crucial for predicting the delivery of many different types of bioactive molecules from an electrospun scaffold for tissue engineering applications.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: J J
authors.initials: JJ
authors.lastname: Yoo
authors.forename: A
authors.initials: A
authors.lastname: Atala
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004800:Enzymes, Immobilized / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D055595:Mechanical Phenomena / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000008:administration & dosage*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D034421:Sus scrofa; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000588:Amines; D003432:Cross-Linking Reagents; D004800:Enzymes, Immobilized; D011091:Polyesters; C016240:polycaprolactone; D005780:Gelatin; D006493:Heparin; D009113:Muramidase