Hydrogel surface properties can be modified to form bioactive interfaces to modulate the osteogenic differentiation of stem cells. In this work, a hydrogel made of gelatin methacrylamide (GelMA) and alginate was designed and tested as a scaffold to control stem-cell osteogenic differentiation. The hydrogel's surface was treated with polydopamine (pDA) to create an adhesive layer for the adsorption of the osteoinductive drug dexamethasone (Dex). The presence of the pDA coating enhanced Dex adsorption and retention over 21 days. This effect resulted in a delay in the osteogenic differentiation of hASCs cultured on the hydrogel treated with a pDA layer.

Secretome-based therapies have the potential to become the next generation of viable therapeutic wound repair treatments. However, precise strategies aimed to refine and control the secretome composition are necessary to enhance its therapeutic efficacy and facilitate clinical translation. In this study, we aim to accomplish this by transfecting human adipose-derived stem cells (hASCs) with microRNA-146a, which is a potent regulator of angiogenesis and inflammation. The secretome composition obtained from the transfected hASCs (secretome146a) was characterized and compared to nontransfected hASCs secretome to evaluate changes in angiogenic and anti-inflammatory growth factor, cytokine, and miRNA content. In vitro proliferation, migration, and tubular morphogenesis assays using human umbilical vein endothelial cells (HUVECs) were completed to monitor the proangiogenic efficacy of the secretome146a. Finally, the anti-inflammatory efficacy of the secretome146a was assessed using HUVECs that were activated to an inflammatory state by IL-1β. The resulting HUVEC gene expression and protein activity of key inflammatory mediators were evaluated before and after secretome treatment. Overall, the secretome146a contained a greater array and concentration of therapeutic paracrine molecules, which translated into a superior angiogenic and anti-inflammatory efficacy. Therefore, this represents a promising strategy to produce therapeutic secretome for the promotion of wound repair processes.

Physical techniques for intracellular delivery of exogeneous materials offer an attractive strategy to enhance the therapeutic efficiency of stem cells. However, these methods are currently limited by poor delivery efficiency as well as cytotoxic effects. Here, a high throughput microfluidic device is designed for efficient (≈85%) cytosolic delivery of exogenous macromolecules with minimal cell death (less than 10%). The designed microfluidic device enables the generation of transient pores as the cells pass through the micron‐sized constrictions (6–10 µm) leading to the passive diffusion of extracellular cargos into the cell cytosol. Specifically, the microfluidic system is designed to induce a double deformation on the cell membrane at the squeezing zones to maximize intracellular delivery. Additionally, the flow rate, ionic concentration, and the molecular weight of the cargo are optimized for maximum efficiency. The optimized device enables cytosolic diffusion of small (3 kDa) and large molecules (70 kDa) without inducing any apoptotic effect. Overall, this double cell deformation platform offers new opportunities to rapidly and efficiently deliver extracellular cargo into stem cells without affecting their viability and functionality.

Gellan gum-based hydrogels display limited cell adhesion ability due to the absence of cell-anchorage points usually present in proteins found in the extracellular matrix (ECM). This issue limits their use in the biomedical field as scaffolds to promote tissue repair. Our work addresses this challenge by investigating the use of polydopamine (pDA) as a bioactive layer to improve the surface and biological properties of gellan gum-based hydrogels cross-linked using carbodiimide chemistry. Upon treatment with a pDA layer, the hydrogel displayed an increase in wettability and swelling properties. This change in physical properties had a direct impact on the biological properties of the scaffolds. Precisely, human adipose-derived stem cells (hASCs) seeded on the pDA coated gellan gum hydrogels displayed larger cell area, increased proliferation rate, and enhanced gene expression of focal adhesion and cytoskeletal proteins. Overall, the findings of this research support the use of pDA coating as a possible approach to improve the biological features of gellan gum-based scaffolds and modulate stem cell morphology and proliferation.

Hydrogels can be fabricated and designed to exert direct control over stem cells' adhesion and differentiation. In this study, we have investigated the use of polydopamine (pDA)‐treatment as a binding platform for bioactive compounds to create a versatile gelatin–alginate (Gel–Alg) hydrogel for tissue engineering applications. Precisely, pDA was used to modify the surface properties of the hydrogel and better control the adhesion and osteogenic differentiation of human adipose‐derived stem cells (hASCs). pDA enabled the adsorption of different types of bioactive molecules, including a model osteoinductive drug (dexamethasone) as well as a model pro‐angiogenic peptide (QK). The pDA treatment efficiently retained the drug and the peptide compared to the untreated hydrogel and proved to be effective in controlling the morphology, cell area, and osteogenic differentiation of hASCs. Overall, the findings of this study confirm the efficacy of pDA treatment as a valuable strategy to modulate the biological properties of biocompatible Gel–Alg hydrogels and further extend their value in regenerative medicine.