title: A 3D aligned microfibrous myocardial tissue construct cultured under transient perfusion.
abstract: The goal of this study was to design and develop a myocardial patch to use in the repair of myocardial infarctions or to slow down tissue damage and improve long-term heart function. The basic 3D construct design involved two biodegradable macroporous tubes, to allow transport of growth media to the cells within the construct, and cell seeded, aligned fiber mats wrapped around them. The microfibrous mat housed mesenchymal stem cells (MSCs) from human umbilical cord matrix (Wharton's Jelly) aligned in parallel to each other in a similar way to cell organization in native myocardium. Aligned micron-sized fiber mats were obtained by electrospinning a polyester blend (PHBV (5% HV), P(L-D,L)LA (70:30) and poly(glycerol sebacate) (PGS)). The micron-sized electrospun parallel fibers were effective in Wharton's Jelly (WJ) MSCs alignment and the cells were able to retract the mat. The 3D construct was cultured in a microbioreactor by perfusing the growth media transiently through the macroporous tubing for two weeks and examined by fluorescence microscopy for cell distribution and preservation of alignment. The fluorescence images of thin sections of 3D constructs from static and perfused cultures confirmed enhanced cell viability, uniform cell distribution and alignment due to nutrient provision from inside the 3D structure.
authors.affiliation: BIOMAT, Dept. of Biological Sciences, Biotechnology Research Unit, Middle East Technical University, Ankara, Turkey.
authors.forename: Halime
authors.initials: H
authors.lastname: Kenar
authors.forename: Gamze T
authors.initials: GT
authors.lastname: Kose
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.forename: Vasif
authors.initials: V
authors.lastname: Hasirci
mesh_terms: D019149:Bioreactors; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000737:chemistry / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D003651:Decanoates / Q000737:chemistry; D055119:Elastic Modulus; D015870:Gene Expression / Q000235:genetics; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D026161:MADS Domain Proteins / Q000235:genetics; D064326:MEF2 Transcription Factors; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics; D010477:Perfusion; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D020825:T-Box Domain Proteins / Q000235:genetics; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics; D014470:Umbilical Cord / Q000166:cytology; D055682:Viscoelastic Substances / Q000737:chemistry; D000094122:Polyhydroxybutyrates
chemical_list: D024042:Collagen Type I; D004268:DNA-Binding Proteins; D003651:Decanoates; D005990:Glycerol; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D011091:Polyesters; D011108:Polymers; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D055682:Viscoelastic Substances; C578035:MEF2A protein, human; C578040:MEF2C protein, human; C578043:MEF2D protein, human; C095552:NKX2-5 protein, human; C103172:T-box transcription factor 5; C117427:ZFPM2 protein, human; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates; C469892:poly(glycerol-sebacate); C033616:poly(lactide)