title: Channelled scaffolds for engineering myocardium with mechanical stimulation.
abstract: The characteristics of the matrix (composition, structure, mechanical properties) and external culture environment (pulsatile perfusion, physical stimulation) of the heart are important characteristics in the engineering of functional myocardial tissue. This study reports on the development of chitosan-collagen scaffolds with micropores and an array of parallel channels (~ 200 µm in diameter) that were specifically designed for cardiac tissue engineering using mechanical stimulation. The scaffolds were designed to have similar structural and mechanical properties of those of native heart matrix. Scaffolds were seeded with neonatal rat heart cells and subjected to dynamic tensile stretch using a custom designed bioreactor. The channels enhanced oxygen transport and facilitated the establishment of cell connections within the construct. The myocardial patches (14 mm in diameter, 1-2 mm thick) consisted of metabolically active cells that began to contract synchronously after 3 days of culture. Mechanical stimulation with high tensile stress promoted cell alignment, elongation, and expression of connexin-43 (Cx-43). This study confirms the importance of scaffold design and mechanical stimulation for the formation of contractile cardiac constructs.
authors.affiliation: Department of Mechanical Engineering, Tsinghua University & Key Laboratory for Advanced Materials Processing Technology, Ministry of Education of China, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, USA.
authors.forename: Leo Q
authors.initials: LQ
authors.lastname: Wan
authors.affiliation: Department of Mechanical Engineering, Tsinghua University & Key Laboratory for Advanced Materials Processing Technology, Ministry of Education of China, Beijing, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Marsano
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Maidhof
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, USA.
authors.forename: Miri
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Mechanical Engineering, Tsinghua University & Key Laboratory for Advanced Materials Processing Technology, Ministry of Education of China, Beijing, China.
authors.forename: Yongnian
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, USA. gv2131@columbia.edu.
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
mesh_terms: D000818:Animals; D019149:Bioreactors; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D003094:Collagen / Q000737:chemistry; D018031:Connexin 43 / Q000378:metabolism; D020342:Finite Element Analysis; D006321:Heart / Q000502:physiology*; D008855:Microscopy, Electron, Scanning; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology; D051381:Rats; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; D003094:Collagen; D048271:Chitosan
references.citation: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1278-89
references.pmid: 15539422
references.citation: Circ Res. 2005 Dec 9;97(12):1220-31
references.pmid: 16339494
references.citation: Nat Med. 2008 Feb;14(2):213-21
references.pmid: 18193059
references.citation: Nat Protoc. 2008;3(4):719-38
references.pmid: 18388955
references.citation: Biomaterials. 1999 Jun;20(12):1133-42
references.pmid: 10382829
references.citation: Sci Am. 2004 Nov;291(5):44-51
references.pmid: 15521146
references.citation: Biotechnol Bioeng. 2006 Feb 5;93(2):332-43
references.pmid: 16270298
references.citation: FASEB J. 2000 Apr;14(5):669-79
references.pmid: 10744624
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18129-34
references.pmid: 15604141
references.citation: Nature. 2003 Feb 27;421(6926):884-6
references.pmid: 12606967
references.citation: Nat Med. 2006 Apr;12(4):452-8
references.pmid: 16582915
references.citation: Philos Trans R Soc Lond B Biol Sci. 2007 Aug 29;362(1484):1357-68
references.pmid: 17594967
references.citation: Pharmacol Ther. 2005 Feb;105(2):151-63
references.pmid: 15670624
references.citation: Circulation. 2002 Sep 24;106(12 Suppl 1):I137-42
references.pmid: 12354723
references.citation: Am J Physiol. 1999 Aug;277(2):H433-44
references.pmid: 10444466
references.citation: Circ Res. 2002 Feb 8;90(2):120-2
references.pmid: 11834701
references.citation: Nat Protoc. 2009;4(2):155-73
references.pmid: 19180087
references.citation: Curr Opin Biotechnol. 2004 Oct;15(5):430-4
references.pmid: 15464373
references.citation: Biotechnol Bioeng. 2007 Jul 1;97(4):962-75
references.pmid: 17195988
references.citation: Circ Res. 2002 Feb 8;90(2):223-30
references.pmid: 11834716
references.citation: Am J Physiol Heart Circ Physiol. 2004 Feb;286(2):H507-16
references.pmid: 14551059
references.citation: Curr Opin Cell Biol. 2007 Oct;19(5):578-83
references.pmid: 17942296
references.citation: Circ Res. 2005 Jul 8;97(1):8-15
references.pmid: 16002755