Because differentiation of mesenchymal stem cells (MSCs) is enacted through the integration of soluble signaling factors and physical cues, including substrate architecture and exogenous mechanical stimulation, it is important to understand how micro-patterned biomaterials may be optimized to enhance differentiation for the formation of functional soft tissues. In the present work, macroscopic strain applied to MSCs in an aligned nanofibrous microenvironment elicited cellular and nuclear deformations that varied depending on scaffold orientation. Reorientation of aligned, oriented MSCs corresponded at the microscopic scale with the affine approximation of their deformation based on macroscopic strains. Moreover, deformations at the subcellular scale corresponded with scaffold orientation, with changes in nuclear shape depending on the direction of substrate alignment. Notably, these deformations induced changes in gene expression that were also dependent on scaffold and cell orientations. These findings demonstrate that directional biases in substrate microstructure convey direction-dependent mechanosensitivity to MSCs and provide an experimental framework in which to explore the mechanistic underpinnings of this response.

Hierarchically 2D/3D mesoporous-macroporous bioactive glasses (MMBG) with good molding capabilities and compressive modulus were synthesized by sol-gel method and evaporation-induced self-assembly process in the presence of both nonionic triblock copolymers, EO(70)PO(20)EO(70) (P123) or EO(100)PO(65)EO(100) (F127), templates and methyl cellulose template. P123 or F127 acts as both a template, inducing the formation of mesopore, and an effective dispersant of MC, which produces macropores. In vitro bioactivity studies were carried out in simulated body fluid and showed superior bone-forming bioactivities of hierarchical MMBG. Human osteoblastlike cells, MG63, were seeded on MMBG and were determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyl-tetrazolium bromide] assay to confirm biocompatibilities of MMBG.

The topical application of TPA (12-O-tetradecanoylphorbol-13-acetate) to animal skin or direct treatment of TPA to cell cultures leads to inflammatory responses by enhancing cyclooxygenase 2 (COX-2) expression, and specific COX-2 inhibitors counteract this kind of inflammatory response. Furthermore, suppression of these inflammatory events by dietary-origin chemopreventive agents can provide a potential strategy to control carcinogenesis. In this in vivo study, the mammary glands of mature female rats were treated with TPA, and then the effects of genistein alone or in combination with capsaicin on suppression of inflammatory responses were examined. The combined effects of genistein and capsaicin on COX-2, pJNK, pERK, and pp38 expressions were additive or nonadditive, depending on signals tested. In vitro MCF-7 breast cancer cells, the apoptotic bodies as shown with Hoechst 33342 dye, exhibited a synergistic effect between genistein and capsaicin. The abilities of genistein alone or in combination with capsaicin in inhibiting breast cancer cell proliferation through the modulation of AMPK and COX-2 were tested. AMPK activation by genistein in combination with capsaicin is critical for inhibiting COX-2. We propose that genistein in combination with capsaicin exerts anti-inflammatory and anticarcinogenic properties through the modulation of AMPK and COX-2 and possibly various mitogen-activated protein kinases synergistically or nonsynergistically.

Hierarchically mesoporous−giantporous bioactive glass/poly ϵ-caprolactone composite scaffolds with good molding capabilities, mechanical properties, bioactivities, and biocompatibilities in vitro, which may find potential applications in tissue engineering and drug storage, were prepared using a combination of the sol–gel, polymer templating, and rapid prototyping techniques with a heat-controlled blowing system.