title: Scaffold-free tissue engineering: organization of the tissue cytoskeleton and its effects on tissue shape.
abstract: Work described herein characterizes tissues formed using scaffold-free, non-adherent systems and investigates their utility in modular approaches to tissue engineering. Immunofluorescence analysis revealed that all tissues formed using scaffold-free, non-adherent systems organize tissue cortical cytoskeletons that appear to be under tension. Tension in these tissues was also evident when modules (spheroids) were used to generate larger tissues. Real-time analysis of spheroid fusion in unconstrained systems illustrated modular motion that is compatible with alterations in tensions, due to the process of disassembly/reassembly of the cortical cytoskeletons required for module fusion. Additionally, tissues generated from modules placed within constrained linear molds, which restrict modular motion, deformed upon release from molds. That tissue deformation is due in full or in part to imbalanced cortical actin cytoskeleton tensions resulting from the constraints imposed by mold systems is suggested from our finding that treatment of forming tissues with Y-27632, a selective inhibitor of ROCK phosphorylation, reduced tissue deformation. Our studies suggest that the deformation of scaffold-free tissues due to tensions mediated via the tissue cortical cytoskeleton represents a major and underappreciated challenge to modular tissue engineering.
authors: Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, BSB 626, MSC 508, Charleston, SC, 29425, USA.
authors: Caitlin A
authors: CA
authors: Czajka
authors: Agnes Nagy
authors: AN
authors: Mehesz
authors: Thomas C
authors: TC
authors: Trusk
authors: Michael J
authors: MJ
authors: Yost
authors: Christopher J
authors: CJ
authors: Drake
mesh_terms: D000199:Actins / Q000502:physiology; D000328:Adult; D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000502:physiology*; D055119:Elastic Modulus; D005347:Fibroblasts; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D032389:Myocytes, Smooth Muscle; D009218:Myosins / Q000502:physiology; D012685:Sepharose; D023822:Tissue Engineering
chemical_list: D000199:Actins; D012685:Sepharose; D009218:Myosins