Abstract
Coordinated investigations into the interactions between biologically mimicking (biomimetic) material constructs and stem cells advance the potential for the regeneration and possible direct replacement of diseased cells and tissues. Any clinically relevant therapies will require the development and optimization of methods that mass produce fully functional cells and tissues. Despite advances in the design and synthesis of biomaterial scaffolds, one of the biggest obstacles facing tissue engineering is understanding how specific extracellular cues produced by biomaterial scaffolds influence the proliferation and differentiation of various cell sources. Matrix elasticity is one such tailorable property of synthetic scaffolds that is known to differ between tissues. Here, we investigate the interactions between an elastically tailorable polyethylene glycol (PEG)-based hydrogel platform and human bone marrow-derived mesenchymal stem cells (hMSCs). For these studies, two different hydrogel compositions with elastic moduli in the ranges of 50–60 kPa and 8–10 kPa were implemented. Our findings demonstrate that the different elasticities in this platform can produce changes in hMSC morphology and proliferation, indicating that the platform can be implemented to produce changes in hMSC behavior and cell state for a broad range of tissue engineering and regenerative applications. Furthermore, we show that the platform’s different elasticities influence stem cell differentiation potential, particularly when promoting stem cell differentiation toward cell types from tissues with stiffer elasticity. These findings add to the evolving and expanding library of information on stem cell–biomaterial interactions and opens the door for continued exploration into PEG-based hydrogel scaffolds for tissue engineering and regenerative medicine applications.
Highlights
Parallel advances in biologically mimicking material constructs and in stem cell technologies enable the restoration and direct replacement of diseased cells and tissues
Bone marrow-derived human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded on the hydrogel scaffolds and after 72 hours a viability assay was performed to determine if the cells survived on each of the three surfaces: tissue culture plates, soft hydrogels and stiff hydrogels
We demonstrated that PEG dimetharcylate (PEGDMA) hydrogels with elasticities within a physiologically relevant range (8–60 kPa) can be generated by varying the molecular weight of the polymer [17]
Summary
Parallel advances in biologically mimicking (biomimetic) material constructs and in stem cell technologies enable the restoration and direct replacement of diseased cells and tissues. To achieve these outcomes clinically, fully functional cells and tissues must be produced on a large scale [1]. Despite advances in the design and synthesis of biomaterial scaffolds, one of the biggest obstacles facing tissue engineering is a lack of understanding regarding the influence of extracellular cues on cell proliferation and differentiation. The extracellular matrix (ECM) is a highly defined and specialized microenvironment, which is essential for tissue development and function. Matrix elasticity is one mechanical property of the ECM that differs between tissues and can be manipulated in synthesized scaffolds The ultimate decision of a cell to differentiate, proliferate, migrate, apoptose or perform other functions is a coordinated response to the physical and chemical interactions with these ECM effectors [2].
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