Interaction of Human Mesenchymal Stem Cells with Soft Nanocomposite Hydrogels Based on Polyethylene Glycol and Dendritic Polyglycerol

Abstract

Keeping the stemness of human mesenchymal stem cells (hMSCs) and their adipocyte differentiation potential is critical for clinical use. However, these features are lost on traditional substrates. hMSCs have often been studied on stiff materials whereas culturing hMSCs in their native niche increases their potential. Herein, a patterned hydrogel nanocomposite with the stiffness of liver tissues is obtained without any molding process. To investigate hMSCs' mechanoresponse to the material, the RGD spacing units and the stiffness of the hydrogels are dually tuned via the linker length. This work suggests that hMSCs' locomotion is influenced by the nature of the hydrogel layer (bulk or thin film). Contrary to on bulk surfaces, cell traction occurs during cell spreading on thin films. In addition, hMSCs' spreading behavior varies from shorter to longer linker-based hydrogels, where on both surfaces hMSCs maintains their stemness as well as their adipogenic differentiation potential with a higher number of adipocytes for nanocomposites with a longer polymer linker. Overall, this work addresses the need for a new alternative for hMSCs culture allowing the cells to differentiate exclusively into adipocytes. This material represents a cell-responsive platform with a tissue-mimicking architecture given by the mechanical and morphological properties of the hydrogel.

The Fabrication of a Gellan Gum-Based Hydrogel Loaded With Magnesium Ions for the Synergistic Promotion of Skin Wound Healing

“…This precursor hydrogel was prepared by heated acrylamide and GG monomer solutions, in which acrylamide was crosslinked by a chemical agent, and GG was crosslinked by metal Mg 2+ ions, respectively. The poly-acrylamide (PAM) provides the high swelling ratio with good mechanical properties to make up the insufficiency of GG ( Distler and Boccaccini, 2020 ; Randriantsilefisoa et al, 2020 ). More importantly, this dynamic dissociation and reassociation of the “GG-Mg 2+ ” coordination bond enables the Mg 2+ ions to be delivered into the burn wound in a stable and controlled manner.…”

Advances in hydrogel-based vascularized tissues for tissue repair and drug screening

“…Although the perfusable vascular analogs have exhibited promising results towards the construction of various organs in vitro , the utilization of such biomimetic constructs in tissue regeneration upon clinical transplantation place high demands on the vascular alignment, which still remains limited for regeneration and implantation of large-scale engineered tissues, such as skeletal muscle, shin epithelium, liver, and other major organs [ [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] ]. Indeed, capillaries are the places where blood and tissues exchange substances, including nutrition and waste products [ 62 , 63 ].…”

“…Liang and colleagues demonstrated the physical interpenetration and covalent crosslinking between GelMA/N-acryloyl glycinamide (GelMA/NAGA) hydrogel networks and nanoclay, which could remarkably enhance the tensile strength, Yong's modulus, anti-fatigue performance, stretchability of the hydrogel, leading to the large-scale length microtubes and endothelialization of hydrogel microtubes after seeding with HUVECs [ 89 ]. In addition to the tailored mechanical performance, developing nanocomposite-based hydrogels with specific functionality, such as ion release, stimuli response, and electrical conductivity, provides enormous opportunities in developing advanced hydrogel systems [ 21 , 22 , 26 , 41 , 57 , 103 , [108] , [109] , [110] , [111] , [112] ]. Considering these advantages in both enhancing physical properties and facilitating cellular activities, the functional nano- or micro-composite hydrogels for engineering vascularized tissues will be further discussed in Section 3.2.3 .…”

“…An impressive spectrum of cell biology, versatile hydrogels, and clinical pathology has enabled the formation of 3D tissue analogs with promoted vascularization. To date, an extensive study has demonstrated various organ types that can be mimicked by hydrogels, including but not limited to bone [ 77 , 95 , [163] , [164] , [165] ], kidney [ [52] , [53] , [54] ], liver [ [55] , [56] , [57] ], lung [ 160 , 166 , 167 ], muscle [ [58] , [59] , [60] , [61] ], and brain [ 138 , 168 ]. Ultimately, the generation of these reproducible and accurate 3D organoids has extended the downstream translational applications, including tissue regeneration ( Table 3 ), organ-on-chips ( Table 4 ), and drug screening ( Table 5 ).…”

Adaptable hydrogel with reversible linkages for regenerative medicine: Dynamic mechanical microenvironment for cells

“…Substrates with high stiffness were proven to be helpful for directional differentiation of stem cells, which would cause loss of stemness [ [115] , [116] , [117] ]. Previous studies focus on matrix stiffness, topological morphology, and other interface structure [ 118 , 119 ]. However, how to maintain stemness in 3D culture is still difficult.…”