Spatial micro-variation of 3D hydrogel stiffness regulates the biomechanical properties of hMSCs

Abstract

Human mesenchymal stem cells (hMSCs) are one of the most promising candidates for cell-based therapeutic products. Nonetheless, their biomechanical phenotype after in vitro expansion is still unsatisfactory, for example, restricting the efficiency of microcirculation of delivered hMSCs for further cell therapies. Here, we propose a scheme using maleimide-dextran hydrogel with locally varied stiffness in microscale to modify the biomechanical properties of hMSCs in three-dimensional (3D) niches. We show that spatial micro-variation of stiffness can be controllably generated in the hydrogel with heterogeneously cross-linking via atomic force microscopy measurements. The result of 3D cell culture experiment demonstrates the hydrogels trigger the formation of multicellular spheroids, and the derived hMSCs could be rationally softened via adjustment of the stiffness variation (SV) degree. Importantly, in vitro, the hMSCs modified with the higher SV degree can pass easier through capillary-shaped micro-channels. Further, we discuss the underlying mechanics of the increased cellular elasticity by focusing on the effect of rearranged actin networks, via the proposed microscopic model of biomechanically modified cells. Overall, this work highlights the effectiveness of SV-hydrogels in reprogramming and manufacturing hMSCs with designed biomechanical properties for improved therapeutic potential.

Synergies of Human Umbilical Vein Endothelial Cell-Laden Calcium Silicate-Activated Gelatin Methacrylate for Accelerating 3D Human Dental Pulp Stem Cell Differentiation for Endodontic Regeneration

“…The mechanical property of a hydrogel is an important factor as it is known to influence cellular morphology, which in turn affects cellular functions and behaviors [33]. Stiffer hydrogels were known to enhance cytoskeletal organization, thus increasing osteoblastic/odontogenic differentiation and proliferation of stem cells [34]. Furthermore, numerous results had proved that alginate coupled with RGD motifs such as gelatin significantly enhanced cellular adhesion, migration, proliferation, and differentiation as alginate itself does not promote cellular activities due to the lack of cellular adhesion motifs [35].…”

Linking metastatic potential and viscoelastic properties of breast cancer spheroids via dynamic compression and relaxation in microfluidics

“…Microfluidics provides a powerful platform to explore the viscoelastic properties of cancer spheroids within confined environment, due to its tunable geometries and dimensions [21]. Recent works involved microfluidic devices to study spheroid mechanics via micropipette aspiration (MPA) in a high-throughput manner [22], or via compressing cellular aggregates in microchannels, to assess viscoelastic properties associated with the cell rearrangement and cell shape within the aggregate [23,24]. Despite the valuable insights on the viscoelastic properties of tumor models gained from these studies, the relationship between the intrinsic viscoelastic characteristics of cancer spheroids and the degree of malignancy remains to be elucidated.…”

3D bioprinting of tyramine modified hydrogels under visible light for osteochondral interface

“…Natural hydrogels such as gelatin, alginate (Alg) [14], and carboxymethyl cellulose (CMC) [15] in combination with their hybrids [16], have shown promising results in tissue engineering of OC defects, potentially stimulating the formation of extracellular matrix (ECM) [17]. An optimal hydrogel matrix for bone and cartilage engineering should encourage cell growth/ proliferation, preserve chondrocyte/osteoblast morphologies, and stimulate chondrogenic/osteogenic differentiation of stem cells for OC interface [1,18]. To enhance the mechanical properties of these hydrogels, several strategies including various crosslinking mechanisms [19][20][21][22], reinforcing with stiff materials [4,23,24], and increasing crosslinking density [25][26][27] have been developed.…”