Toward Artificial Cell-Mediated Tissue Engineering: A New Perspective.

The fast-growing pace of regenerative medicine research has allowed the development of a range of novel approaches to tissue engineering applications. Until recently, the main points of interest in the majority of studies have been to combine different materials to control cellular behavior and use different techniques to optimize tissue formation, from 3-D bioprinting to in situ regeneration. However, with the increase of the understanding of the fundamentals of cellular organization, tissue development, and regeneration, has also come the realization that for the next step in tissue engineering, a higher level of spatiotemporal control on cell-matrix interactions is required. It is proposed that the combination of artificial cell research with tissue engineering could provide a route toward control over complex tissue development. By equipping artificial cells with the underlying mechanisms of cellular functions, such as communication mechanisms, migration behavior, or the coherent behavior of cells depending on the surrounding matrix properties, they can be applied in instructing native cells into desired differentiation behavior at a resolution not to be attained with traditional matrix materials.

In situ and non-cytotoxic cross-linking strategy for 3D printable biomaterials.

3D bioprinting allows the production of patient-specific tissue constructs with desired structural characteristics such as high resolution, controlled swelling degree, and controlled degradation behavior by mostly using hydrogels. Crosslinking of hydrogels is an essential parameter in bioprinting applications, which is beneficial for tuning structural specifications. In this study, gelatin-alginate-whey protein isolate based hydrogels have been used for 3D printing structures in a layer-by-layer fashion. These structures were cross-linked by the Amino Acid (monomer) Decorated and Light Underpinning Conjugation Approach (ANADOLUCA) method, which is a unique, non-invasive photosensitive cross-linking technique for protein-based mixtures. In that aim, hydrogel properties (e.g., printability, biocompatibility, rheologic and mechanical behavior) and cross-linking properties (e.g., swelling and degradation behavior) were studied. Results were compared with UV and ionic cross-linking techniques, which are the abundantly used techniques in such studies. The results showed that the ANADOLUCA method can be used for in situ cross-linking under mild conditions for the printing of bio-inks, and the proposed method can be used as an alternative for UV-based and chemical cross-linking techniques.