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This review focuses on novel applications based on multifunctional materials to actuate biological processes. The first section of the work revisits the current knowledge on mechanically dependent biological processes across several scales from subcellular and cellular level to the cell-collective scale (continuum approaches). This analysis presents a wide variety of mechanically dependent biological processes on nervous system behaviour; bone development and healing; collective cell migration. In the second section, this review presents recent advances in smart materials suitable for use as cell substrates or scaffolds, with a special focus on magneto-active polymers (MAPs). Throughout the manuscript, both experimental and computational methodologies applied to the different treated topics are reviewed. Finally, the use of smart polymeric materials in bioengineering applications is discussed.

Cell spheroids have recently emerged as an effective tool to recapitulate native microenvironments of living organisms in an in vitro scenario, increasing the reliability of the results obtained and broadening their applications in regenerative medicine, cancer research, disease modeling and drug screening. In this study the generation of spheroids containing primary human dermal fibroblasts (dHFs) was approached using the two-widely employed methods: hanging-drop (HD) and U-shape low adhesion plate (LA-plate). Moreover, extrusion-based 3D bioprinting was introduced to achieve a standardized and scalable production of cell spheroids, decreasing considerably the possibilities of human error. This was ensured when U-shape LA-plates were used, showing an 85% formation efficiency, increasing up to a 98% when it was automatized using the 3D bioprinting technologies. However, sedimentation effect within the cartridge led to a reduction of 20% in size of the spheroid during the printing process. Hyaluronic acid (HA) was chosen as viscosity enhancer to supplement the bioink and overcome cell sedimentation within the cartridge due to the high viability values exhibited by the cells – around 80% – at the used conditions. Finally, ANCOVA analysis of spheroid size over time for different printing conditions stand out HA 0.4% (w/v) 60 kDa as the viscosity-improved bioink that exhibit the highest cell viability and spheroid formation percentages. Besides, not only did it ensure cell spheroid homogeneity over time, reducing cell sedimentation effects, but also wider spheroid diameters over time with less variability, outperforming significantly manual loading.

The extracellular matrix (ECM) is a structural network that comprises the bulk of the tissues. It acts as a supporting scaffold for the cells to develop their function and plays an active role in many processes such as proliferation and migration. Therefore, the ECM is an interesting object of study for regenerative medicine. In this article we make an extensive review of two key components of the ECM: the glycosaminoglycan Hyaluronic Acid (HA) and the proteoglycan Versican (Ver). These two molecules are present in the skin ECM and play active roles in processes such as differentiation, wound healing, hair follicle cycle and development. In our opinion, further biological insights in these two molecules and their interaction will be of great importance for skin tissue engineering applications.