Hypertension is a significant risk factor for diverse cerebrovascular diseases ranging from stroke to arteriovenous malformations and saccular aneurysms. Our increasing understanding of vascular mechanobiology reveals that changes in mechanical stimuli, such as increased blood pressure, alter basic cellular functions including the production and degradation of extracellular matrix as well as proliferation, migration, and apoptosis. Understanding changes in the biomechanical properties of the vascular wall is fundamental to correlating mechanobiological responses with the altered loads. In this paper, we present the first biomechanical data on a large cerebral artery in terms of the time of development of hypertension in maturity. Specifically, we report rapid changes in both the structural and the material stiffness of the passive basilar artery in a novel aortic-coarctation model of hypertension in the mini-pig. Histological measurements reveal associated increases in fibrillar collagens in the media and adventitia as well as increased smooth muscle in the media. That such dramatic changes occur within 2 weeks of the initiation of hypertension in maturity necessitates a detailed study of the early changes as well as the potential to reverse these changes at later times.

Little is known about the precise mechanical stimuli that cells sense and respond to as they maintain or refashion the extracellular matrix in multiaxially loaded native or bioengineered tissues. Such information would benefit many areas of research involving soft tissues, including tissue morphogenesis, wound healing, and tissue engineering. A custom tissue culture device has been constructed that can impart well defined biaxial stretches on cruciform-shaped, fibroblast-seeded collagen gels and be mounted on the stage of a nonlinear optical microscopy (NLOM) system for microscopic characterization of matrix organization. The cruciform geometry permitted direct comparison of matrix (re-) organization within regions of the collagen gel exposed to either uniaxial or biaxial boundary conditions and examined by NLOM for up to six days. In addition, sequential NLOM measurements of collagen fiber orientations within gels while stretched, unloaded, or decellularized delineated contributions of applied stretches, cell-mediated tractions and matrix remodeling on the measured distributions. The integration of intravital NLOM with novel bioreactors enables visualization of dynamic tissue properties in culture.

(EW) S U M M A R Y Arteries undergo marked structural and functional changes in human and experimental hypertension that generally involve smooth muscle cell (SMC) hypertrophy/ hyperplasia as well as abnormal extracellular matrix turnover. In this study we examined time courses of changes in SMC activity and matrix protein content in a novel mini-pig aortic coarctation model. Cell proliferation was evaluated by immunostaining of Ki-67, apoptosis was assessed by TUNEL, and phenotypic changes were monitored by immunostaining three SMC contractile markers (caldesmon, calponin, and smoothelin). Changes in medial collagen and elastin were examined by picrosirius red and Verhoeff-van Gieson staining, respectively. LabVIEW-based image analysis routines were developed to objectively and efficiently quantify the (immuno)histochemical results. We found that significant cell proliferation and matrix production occurred in the early stages of this coarctation model and then declined gradually; the SMCs also tended to exhibit a less contractile phenotype following these cellular and extracellular changes. Specifically, different aspects of the phenotypic changes associated with hypertension occurred at different rates: cell proliferation and collagen production occurred early and peaked by 2 weeks, whereas changes in contractile protein expression continued to decrease over the entire 8-week study period. Temporal changes found in this study emphasize the importance of simultaneously tracing time courses of SMC growth and differentiation as well as matrix protein production and content. SMCs are multifunctional, and caution must be used to not overdefine phenotype. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 56:359-370, 2008)

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Poly(glycerol sebacate) (PGS) has been used successfully as a scaffolding material for soft tissue engineering. PGS scaffolds, however, are usually mechanically isotropic, which may restrict their use in tissue repairs as many soft tissues in the body have anisotropic mechanical behaviors. Although various methods have been used to fabricate anisotropic scaffolds, it remains challenging to make anisotropic scaffolds from thermoset PGS. Here a new, simple method to fabricate an anisotropic PGS membrane which can then be used to construct thicker three-dimensional anisotropic scaffolds was developed. First, an aligned sacrificial poly(vinyl alcohol) fibrous membrane was prepared by electrospinning. The fibrous membrane was then partially immersed in PGS prepolymer solution, resulting in a composite membrane upon drying. After curing, the sacrificial fibers within the membrane were removed by water, supposedly leaving aligned cylindrical pores in the membrane. Both SEM and AFM illustrated aligned grooves on the surface of the resultant PGS membrane, indicating the successful removal of sacrificial fibers. The PGS membrane was validated to be mechanically anisotropic using uniaxial tensile testing along and perpendicular to the predominant pore direction. The in vitro cytocompatibility of the PGS membrane was confirmed. As a demonstration of its potential application in vascular tissue engineering, a tubular scaffold was constructed by wrapping a stack of two axisymmetric pieces of the anisotropic PGS membranes on a mandrel. The compliance of the scaffold was found to depend on the pitch angle of its double helical structure, imitating the anisotropic mechanical behavior of the arterial media. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 760-770, 2018.