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Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: Implications for engineered heart valve tissues

Paper ID Volume ID Publish Year Pages File Format Full-Text
11276 729 2006 13 PDF Available
Title
Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: Implications for engineered heart valve tissues
Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) are relatively accessible and exhibit a pluripotency suitable for cardiovascular applications such as tissue-engineered heart valves (TEHVs). Recently, Sutherland et al. [From stem cells to viable autologous semilunar heart valve. Circulation 2005; 111(21): 2783–91] demonstrated that BMSC-seeded TEHV can successfully function as pulmonary valve substitutes in juvenile sheep for at least 8 months. Toward determining appropriate mechanical stimuli for use in BMSC-seeded TEHV cultivation, we investigated the independent and coupled effects of two mechanical stimuli physiologically relevant to heart valves—cyclic flexure and laminar flow (i.e. fluid shear stress)—on BMSC-mediated tissue formation. BMSC isolated from juvenile sheep were expanded and seeded onto rectangular strips of nonwoven 50:50 blend poly(glycolic acid) (PGA) and poly(l-lactic acid) (PLLA) scaffolds. Following 4 days static culture, BMSC-seeded scaffolds were loaded into a novel flex-stretch-flow (FSF) bioreactor and incubated under static (n=12n=12), cyclic flexure (n=12n=12), laminar flow (avg. wall shear stress=1.1505 dyne/cm2; n=12n=12) and combined flex-flow (n=12n=12) conditions for 1 (n=6n=6) and 3 (n=6n=6) weeks. By 3 weeks, the flex-flow group exhibited dramatically accelerated tissue formation compared with all other groups, including a 75% higher collagen content of 844±278 μg/g wet weight (p<0.05p<0.05), and an effective stiffness (E) value of 948±233 kPa. Importantly, collagen and E values were not significantly different from values measured for vascular smooth muscle cell (SMC) -seeded scaffolds incubated under conditions of flexure alone [Engelmayr et al. The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. Biomaterials 2005; 26(2): 175–87], suggesting that BMSC-seeded TEHV can be optimized to yield results comparable to SMC-seeded TEHV. We thus demonstrated that cyclic flexure and laminar flow can synergistically accelerate BMSC-mediated tissue formation, providing a basis for the rational design of in vitro conditioning regimens for BMSC-seeded TEHV.

Keywords
Tissue engineering; Mesenchymal stem cell; Bioreactor; Flexure; Flow; Fluid shear stress
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Cyclic flexure and laminar flow synergistically accelerate mesenchymal stem cell-mediated engineered tissue formation: Implications for engineered heart valve tissues
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 27, Issue 36, December 2006, Pages 6083–6095
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us