title: Activated Schwann Cell-Like Cells on Aligned Fibrin-Poly(Lactic-Co-Glycolic Acid) Structures: A Novel Construct for Application in Peripheral Nerve Regeneration.
abstract: Tissue engineering approaches in nerve regeneration search for ways to support gold standard therapy (autologous nerve grafts) and to improve results by bridging nerve defects with different kinds of conduits. In this study, we describe electrospinning of aligned fibrin-poly(lactic-co-glycolic acid) (PLGA) fibers in an attempt to create a biomimicking tissue-like material seeded with Schwann cell-like cells (SCLs) in vitro for potential use as an in vivo scaffold. Rat adipose-derived stem cells (rASCs) were differentiated into SCLs and evaluated with flow cytometry concerning their differentiation and activation status [S100b, P75, myelin-associated glycoprotein (MAG), and protein 0 (P0)]. After receiving the proliferation stimulus forskolin, SCLs expressed S100b and P75; comparable to native, activated Schwann cells, while cultured without forskolin, cells switched to a promyelinating phenotype and expressed S100b, MAG, and P0. Human fibrinogen and thrombin, blended with PLGA, were electrospun and the alignment and homogeneity of the fibers were proven by scanning electron microscopy. Electrospun scaffolds were seeded with SCLs and the formation of Büngner-like structures in SCLs was evaluated with phalloidin/propidium iodide staining. Carrier fibrin gels containing rASCs acted as a self-shaping matrix to form a tubular structure. In this study, we could show that rASCs can be differentiated into activated, proliferating SCLs and that these cells react to minimal changes in stimulus, switching to a promyelinating phenotype. Aligned electrospun fibrin-PLGA fibers promoted the formation of Büngner-like structures in SCLs, which also rolled the fibrin-PLGA matrix into a tubular scaffold. These in vitro findings favor further in vivo testing.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria.
authors.forename: Christina M A P
authors.initials: CM
authors.lastname: Schuh
authors.forename: Tatjana J
authors.initials: TJ
authors.lastname: Morton
authors.forename: Asmita
authors.initials: A
authors.lastname: Banerjee
authors.forename: Christian
authors.initials: C
authors.lastname: Grasl
authors.forename: Heinrich
authors.initials: H
authors.lastname: Schima
authors.forename: Robert
authors.initials: R
authors.lastname: Schmidhammer
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.forename: Dominik
authors.initials: D
authors.lastname: Ruenzler
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005337:Fibrin / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D010525:Peripheral Nerves / Q000166:cytology / Q000502:physiology*; D011100:Polyglycolic Acid / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005337:Fibrin