Mechano-active tissue engineering of vascular smooth muscle using pulsatile perfusion bioreactors and elastic PLCL scaffolds.
Blood vessels are subjected in vivo to mechanical forces in a form of radial distention, encompassing cyclic mechanical strain due to the pulsatile nature of blood flow. Vascular smooth muscle (VSM) tissues engineered in vitro with a conventional tissue engineering technique may not be functional, because vascular smooth muscle cells (VSMCs) cultured in vitro typically revert from a contractile phenotype to a synthetic phenotype. In this study, we hypothesized that pulsatile strain and shear stress stimulate VSM tissue development and induce VSMCs to retain the differentiated phenotype in VSM engineering in vitro. To test the hypothesis, rabbit aortic smooth muscle cells (SMCs) were seeded onto rubber-like elastic, three-dimensional PLCL [poly(lactide-co-caprolactone), 50:50] scaffolds and subjected to pulsatile strain and shear stress by culturing them in pulsatile perfusion bioreactors for up to 8 weeks. As control experiments, VSMCs were cultured on PLCL scaffolds statically. The pulsatile strain and shear stress enhanced the VSMCs proliferation and collagen production. In addition, a significant cell alignment in a direction radial to the distending direction was observed in VSM tissues exposed to radial distention, which is similar to that of native VSM tissues in vivo, whereas VSMs in VSM tissues engineered in the static condition randomly aligned. Importantly, the expression of SM alpha-actin, a differentiated phenotype of SMCs, was upregulated by 2.5-fold in VSM tissues engineered under the mechano-active condition, compared to VSM tissues engineered in the static condition. This study demonstrates that tissue engineering of VSM tissues in vitro by using pulsatile perfusion bioreactors and elastic PLCL scaffolds leads to the enhancement of tissue development and the retention of differentiated cell phenotype.
Jeong
Sung In
SI
School of Chemical Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
Kwon
Jae Hyun
JH
Lim
Jin Ik
JI
Cho
Seung-Woo
SW
Jung
Youngmee
Y
Sung
Won Jun
WJ
Kim
Soo Hyun
SH
Kim
Young Ha
YH
Lee
Young Moo
YM
Kim
Byung-Soo
BS
Choi
Cha Yong
CY
Kim
Soo-Ja
SJ
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D004548:Elasticity; D005260:Female; D008422:Materials Testing; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D010477:Perfusion; D010812:Physical Stimulation / Q000295:instrumentation / Q000379:methods; D011091:Polyesters / Q000737:chemistry*; D011673:Pulsatile Flow; D011817:Rabbits; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
D001672:Biocompatible Materials; D011091:Polyesters; C062968:lactide-caprolactone copolymer