The aim of this study is to investigate polyacrylamide‐based hydrogels stress relaxation and the subsequent impact on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Different hydrogels are synthesized by varying the amount of cross‐linker and the ratio between the monomers (acrylamide and acrylic acid), and characterized by compression tests. It has been found that hydrogels containing 18% of acrylic acid exhibit an average relaxation of 70%, while pure polyacrylamide gels show an average relaxation of 15%. Subsequently, hMSCs are cultured on two different hydrogels functionalized with a mimetic peptide of the bone morphogenetic protein‐2 to enable cell adhesion and favor their osteogenic differentiation. Phalloidin staining shows that for a constant stiffness of 55 kPa, a hydrogel with a low relaxation (15%) leads to star‐shaped cells, which is typical of osteocytes, while a hydrogel with a high relaxation (70%) presents cells with a polygonal shape characteristic of osteoblasts. Immunofluorescence labeling of E11, strongly expressed in early osteocytes, also shows a dramatically higher expression for cells cultured on the hydrogel with low relaxation (15%). These results clearly demonstrate that, by fine‐tuning hydrogels stress relaxation, hMSCs differentiation can be directed toward osteoblasts, and even osteocytes, which is particularly rare in vitro.
Notwithstanding the efforts injected in vascular tissue engineering in the past 30 years, the clinical translation of engineered artery constructs is far from being successful. One common approach to improve artery regeneration is the use of cyclic mechanical stimuli to guide cellular remodeling. However, there is a lack of information on the effect of cyclic strain on cells within a 3D environment. To this end, this work explored the effect of gradual increase in stimulation frequency on the response of human umbilical artery smooth muscle cells (HUASMCs) embedded in a 3D collagen matrix. The results demonstrate that, with an applied strain of 5%, the gradual increase of frequency from 0.1 to 1 Hz improved collagen remodeling by HUASMCs compared to samples constantly stimulated at 1 Hz. The expression of collagen, elastin and matrix metalloproteinase-2 (MMP-2) genes was similar at 7 days for gradual and 1 Hz samples which showed lower amounts than static counterparts. Interestingly the mechanical properties of the constructs, specifically the amplitude of the time constants and the elastic equilibrium modulus, were enhanced by gradual increase of frequency. Taken together, these results show an increase in collagen remodeling by the HUASMCs overtime under incremental cyclic mechanical strain. This work suggests that only the in-depth investigation of the effects of stimulation parameters on the behavior of vSMC under cyclic strain in a 3D environment could lead to the design of optimized control strategies for enhanced vascular tissue generation and maturation in bioreactors.
The aim of this study is to investigate the impact of the stiffness and stress relaxation of poly(acrylamide-co-acrylic acid) hydrogels on the osteogenic differentiation of human mesenchymal stem cells (hMSCs).
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