Mechanical compliance is emerging as an important environmental cue that can influence certain cell behaviors, such as morphology and motility. Recent in vitro studies have shown that cells preferentially migrate from less stiff to more stiff substrates; however, much of this phenomenon, termed durotaxis, remains ill-defined. To address this problem, we studied the morphology and motility of vascular smooth muscle cells on well-defined stiffness gradients. Baselines for cell spreading, polarization, and random motility on uniform gels with moduli ranging from 5 to 80 kPa were found to increase with increasing stiffness. Subsequent analysis of the behavior of vascular smooth muscle cells on gradient substrata (0-4 kPa/100 mum, with absolute moduli of 1-80 kPa) demonstrated that the morphology on gradient gels correlated with the absolute modulus. In contrast, durotaxis (evaluated quantitatively as the tactic index for a biased persistent random walk) and cell orientation with respect to the gradient both increased with increasing magnitude of gradient, but were independent of the absolute modulus. These observations provide a foundation for establishing quantitative relationships between gradients in substrate stiffness and cell response. Moreover, these results reveal common features of phenomenological cell response to chemotactic and durotactic gradients, motivating further mechanistic studies of how cells integrate and respond to multiple complex signals.

Abstract-Although the need for a functional arterial replacement is clear, the lower blood flow velocities of small-diameter arteries like the coronary artery have led to the failure of synthetic materials that are successful for large-diameter grafts. Although autologous vessels remain the standard for small diameter grafts, many patients do not have a vessel suitable for use because of vascular disease, amputation, or previous harvest. As a result, tissue engineering has emerged as a promising approach to address the shortcomings of current therapies. Investigators have explored the use of arterial tissue cells or differentiated stem cells combined with various types of natural and synthetic scaffolds to make tubular constructs and subject them to chemical and/or mechanical stimulation in an attempt to develop a functional small-diameter arterial replacement graft with varying degrees of success. Here, we review the progress in all these major facets of the field. Key Words: tissue engineering Ⅲ artery Ⅲ collagen Ⅲ elastin Ⅲ vascular graft I n 2002, more than 500 000 surgical procedures were performed involving replacement of small-caliber blood vessels. 1 Despite a clear clinical need for a functional arterial graft, success has been limited to arterial replacements of large-caliber vessels such as the thoracic and abdominal aorta, arch vessels, iliac, and common femoral arteries; however, small-caliber (Ͻ6 mm) arterial substitutes, which account for a majority of the demand, have generally proved inadequate largely because of acute thrombogenicity of the graft, anastomotic intimal hyperplasia, aneurysm formation, infection, and progression of atherosclerotic disease. 2 The lower blood flow velocities of smaller vessels pose a different set of design criteria and introduce a host of new problems not encountered in large-caliber arterial substitutes where Dacron and expanded polytetrafluorethylene grafts have succeeded.Although autologous vessels, such as the saphenous vein, remain the standard for small diameter grafts, many patients do not have a vessel suitable for use because of vascular disease, amputation, or previous harvest. Moreover, this method requires a second surgical procedure to obtain the vessel. Tissue engineering has emerged as a promising approach to address the shortcomings of current options. Investigators have explored the use of arterial tissue cells combined with various types of natural and synthetic scaffolds to make tubular constructs and subject them to chemical and/or mechanical stimulation in an attempt to develop a functional small-diameter arterial replacement graft with varying degrees of success. There have been several reviews of vascular tissue engineering studies in recent years. [3][4][5][6] Here, we review the progress in Many design criteria have been proposed for the development of a functional small-diameter arterial replacement graft. 2,5,6,9 -13 It must be biocompatible, ie, nonthrombogenic, nonimmunogenic, and resistant to infection, all of which are associated wi...

The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ–organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be used in drug discovery and toxicology studies.