Actuation of Soft Thermoresponsive Hydrogels Mechanically Stimulates Osteogenesis in Human Mesenchymal Stem Cells without Biochemical Factors.

Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple lineages and can be harvested relatively easily from adults, making them a promising cell source for regenerative therapies. While it is well-known how to consistently differentiate MSCs into adipose, chondrogenic, and osteogenic lineages by treatment with biochemical factors, the number of studies exploring how to achieve this with mechanical signals is limited. A relatively unexplored area is the effect of cyclic forces on the MSC differentiation. Recently, our group developed a thermoresponsive N-ethyl acrylamide/N-isopropylacrylamide (NIPAM/NEAM) hydrogel supplemented with gold nanorods that are able to convert near-infrared light into heat. Using light pulses allows for local hydrogel collapse and swelling with physiologically relevant force and frequency. In this study, MSCs are cultured on this hydrogel system with a patterned surface and exposed to intermittent or continuous actuation of the hydrogel for 3 days to study the effect of actuation on MSC differentiation. First, cells are harvested from the bone marrow of three donors and tested for their MSC phenotype, meeting the following criteria: the harvested cells are adherent and demonstrate a fibroblast-like bipolar morphology. They lack the expression of CD34 and CD45 but do express CD73, CD90, and CD105. Additionally, their differentiation potential into adipogenic, chondrogenic, and osteogenic lineages is validated by the addition of standardized differentiation media. Next, MSCs are exposed to intermittent or continuous actuation, which leads to a significantly enhanced cell spreading compared to nonactuated cells. Moreover, actuation results in nuclear translocation of Runt-related transcription factor 2 and the Yes-associated protein. Together, these results indicate that cyclic mechanical stimulation on a soft, ridged substrate modulates the MSC fate commitment in the direction of osteogenesis.

Unveiling the main factors triggering the coagulation at the SiC-blood interface.

Hemocompatibility is the most significant criterion for blood-contacting materials in successful in vivo applications. Prior to the clinical tests, in vitro analyses must be performed on the biomaterial surfaces in accordance with the ISO 10993-4 standards. Designing a bio-functional material requires engineering the surface structure and chemistry, which significantly influence the blood cell activity according to earlier studies. In this study, we elucidate the role of surface terminations and polymorphs of SiC single crystals in the initial stage of the contact coagulation. We present a detailed analysis of phase, roughness, surface potential, wettability, consequently, reveal their effect on cytotoxicity and hemocompatibility by employing live/dead stainings, live cell imaging, ELISA and Micro BCA protein assay. Our results showed that the surface potential and the wettability strongly depend on the crystallographic polymorph as well as the surface termination. We show, for the first time, the key role of SiC surface termination on platelet activation. This dependency is in good agreement with the results of our in vitro analysis and points out the prominence of cellular anisotropy. We anticipate that our experimental findings bridge the surface properties to the cellular activities, and therefore, pave the way for tailoring advanced hemocompatible surfaces.