Mesenchymal stromal cell (MSC)-based cell therapy in acute respiratory diseases is based on MSC secretion of paracrine factors. Several strategies have proposed to improve this are being explored including pre-conditioning the MSCs prior to administration. We here propose a strategy for improving the therapeutic efficacy of MSCs based on cell preconditioning by growing them in native extracellular matrix (ECM) derived from the lung. To this end, a bioink with tunable stiffness based on decellularized porcine lung ECM hydrogels was developed and characterized. The bioink was suitable for 3D culturing of lung-resident MSCs without the need for additional chemical or physical crosslinking. MSCs showed good viability, and contraction assays showed the existence of cell–matrix interactions in the bioprinted scaffolds. Adhesion capacity and length of the focal adhesions formed were increased for the cells cultured within the lung hydrogel scaffolds. Also, there was more than a 20-fold increase of the expression of the CXCR4 receptor in the 3D-cultured cells compared to the cells cultured in plastic. Secretion of cytokines when cultured in an in vitro model of lung injury showed a decreased secretion of pro-inflammatory mediators for the cells cultured in the 3D scaffolds. Moreover, the morphology of the harvested cells was markedly different with respect to conventionally (2D) cultured MSCs. In conclusion, the developed bioink can be used to bioprint structures aimed to improve preconditioning MSCs for therapeutic purposes.
Bacterial nanocellulose (BNC) is usually produced as randomly‐organized highly pure cellulose nanofibers films. Its high water‐holding capacity, porosity, mechanical strength, and biocompatibility make it unique. Ordered structures are found in nature and the properties appearing upon aligning polymers fibers inspire everyone to achieve highly aligned BNC (A‐BNC) films. This work takes advantage of natural bacteria biosynthesis in a reproducible and straightforward approach. Bacteria confined and statically incubated biosynthesized BNC nanofibers in a single direction without entanglement. The obtained film is highly oriented within the total volume confirmed by polarization‐resolved second‐harmonic generation signal and Small Angle X‐ray Scattering. The biosynthesis approach is improved by reusing the bacterial substrates to obtain A‐BNC reproducibly and repeatedly. The suitability of A‐BNC as cell carriers is confirmed by adhering to and growing fibroblasts in the substrate. Finally, the thermal conductivity is evaluated by two independent approaches, i.e., using the well‐known 3ω‐method and a recently developed contactless thermoreflectance approach, confirming a thermal conductivity of 1.63 W mK−1 in the direction of the aligned fibers versus 0.3 W mK−1 perpendicularly. The fivefold increase in thermal conductivity of BNC in the alignment direction forecasts the potential of BNC‐based devices outperforming some other natural polymer and synthetic materials.
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