dvanced functional biobased materials for stem cell-mediated regenerative therapy

Background Understanding and overcoming the limitations of cell survival, immune-mediated rejection, unpredictable cell differentiation, and poor host integration through stem cell-mediated regenerative therapy will still be required to bring this approach into clinical practice. To overcome such obstacles, intelligent functional biobased materials have been developed to guide stem cell behaviour via fine-tuned biomimetic biochemical and biophysical cues. This unique generation of materials includes hydrogels, decellularised extracellular matrices, nanocomposites, scaffolds decorated with biomolecules, and more, which can provide dynamic microenvironments that can be used to modulate mechanotransduction, immunomodulation, angiogenesis, and lineage-specific differentiation. Methods A critical review is presented of the mechanistic crosstalk between stem cells and functional biobased materials, highlighting mechanisms related to materiobiology, mimicking the extracellular matrix, macrophage polarization, and paracrine signaling. We will look at key signaling pathways that determine stem cell fate, which include integrin-mediated focal adhesion, PI3K/Akt, MAPK, and finally YAP/TAZ mechanotransduction, in the context of scaffold stiffness, nanotopography, and biochemical modifications. In addition, we investigate cutting-edge, regenerative techniques such as extracellular vesicle delivery, nanotechnology-based gene modulation, 3D-bioprinting, and stimuli-responsive biomaterials. Specific focus is given to orthopedic stem cell therapy, cardiac stem cell therapy, dental stem cell therapy, and soft tissue stem cell therapies, both in terms of translational viability as well as the inherent constraints. Results Progress has been made in preclinical studies, but the widespread use of an intervention in the clinic is stymied by important issues of biosafety, donor variability, manufacturing standardization, regulatory issues, and the need for long-term validation. Conclusions Beyond the descriptive description, this review provides a unified approach and strategy for “biobased material-guided stem cell fate regulation” with an emphasis on biomaterials as active immunomodulatory and mechanobiological regulators and not passive delivery systems.