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Polymeric matrices mimicking multiple functions of the ECM are expected to enable a material induced regeneration of tissues. Here, we investigated the adipogenic differentiation of human adipose derived mesenchymal stem cells (hADSCs) in a 3D architectured gelatin based hydrogel (ArcGel) prepared from gelatin and L-lysine diisocyanate ethyl ester (LDI) in an one-step process, in which the formation of an open porous morphology and the chemical network formation were integrated. The ArcGel was designed to support adipose tissue regeneration with its 3D porous structure, high cell biocompatibility, and mechanical properties compatible with human subcutaneous adipose tissue. The ArcGel could support initial cell adhesion and survival of hADSCs. Under static culture condition, the cells could migrate into the inner part of the scaffold with a depth of 840 +/- 120 mu m after 4 days, and distributed in the whole scaffold (2mm in thickness) within 14 days. The cells proliferated in the scaffold and the fold increase of cell number after 7 days of culture was 2.55 +/- 0.08. The apoptotic rate of hADSCs in the scaffold was similar to that of cells maintained on tissue culture plates. When cultured in adipogenic induction medium, the hADSCs in the scaffold differentiated into adipocytes with a high efficiency (93 +/- 1%). Conclusively, this gelatin based 3D scaffold presented high cell compatibility for hADSC cultivation and differentiation, which could serve as a potential implant material in clinical applications for adipose tissue reparation and regeneration.
Objective: The behaviors of endothelial cells or mesenchymal stem cells are remarkably influenced by the mechanical properties of their surrounding microenvironments. Here, electrospun fiber meshes containing various mechanical characteristics were developed from polyetheresterurethane (PEEU) copolymers. The goal of this study was to explore how fiber mesh stiffness affected endothelial cell shape, growth, migration, and angiogenic potential of endothelial cells. Furthermore, the effects of the E-modulus of fiber meshes on human adipose-derived stem cells (hADSCs) osteogenic potential was investigated.
Methods: Polyesteretherurethane (PEEU) polymers with various poly(p-dioxanone) (PPDO) to poly (ε-caprolactone) (PCL) weight percentages (40 wt.%, 50 wt.%, 60 wt.%, and 70 wt.%) were synthesized, termed PEEU40, PEEU50, PEEU60, and PEEU70, accordingly. The electrospinning method was used for the preparation of PEEU fiber meshes. The effects of PEEU fiber meshes with varying elasticities on the human umbilical vein endothelial cells (HUVECs) shape, growth, migration and angiogenic potential were characterized. To determine how the E-modulus of fiber meshes affects the osteogenic potential of hADSCs, the cellular and nuclear morphologies and osteogenic differentiation abilities were evaluated.
Results: With the increasing stiffness of PEEU fiber meshes, the aspect ratios of HUVECs cultivated on PEEU materials increased. HUVECs cultivated on high stiffness fiber meshes (4.5 ± 0.8 MPa) displayed a considerably greater proliferation rate and migratory velocity, in addition demonstrating increased tube formation capability, compared with those of the cells cultivated on lower stiffness fiber meshes (2.6 ± 0.8 MPa). Furthermore, in comparison to those cultivated on lower stiffness fiber meshes, hADSCs adhered to the highest stiffness fiber meshes PEEU70 had an elongated shape. The hADSCs grown on the softer PEEU40 fiber meshes showed a reduced nuclear aspect ratio (width to height) than those cultivated on the stiffer fiber meshes. Culturing hADSCs on stiffer fibers improved their osteogenic differentiation potential. Compared with cells cultured on PEEU40, osteocalcin expression and alkaline phosphatase (ALP) activity increased by 73 ± 10% and 43 ± 16%, respectively, in cells cultured on PEEU70.
Conclusion: The mechanical characteristics of the substrate are crucial in the modulation of cell behaviors. These findings indicate that adjusting the elasticity of fiber meshes might be a useful method for controlling the blood vessels development and regeneration. Furthermore, the mechanical characteristics of PEEU fiber meshes might be modified to control the osteogenic potential of hADSCs.
Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that the mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted by and persisted after brief preconditioning with the appropriate microtopography. Moreover, the elevated activation levels of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) in hADSCs were also observed during and after the preconditioning process. These findings underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via transplantation of topographic microstructure preconditioned stem cells.