Therapeutic strategies for skin regeneration based on biomedical substitutes.

Regenerative medicine and tissue engineering (TE) have experienced significant advances in the development of in vitro engineered skin substitutes, either for replacement of lost tissue in skin injuries or for the generation of in vitro human skin models to research. However, currently available skin substitutes present different limitations such as expensive costs, abnormal skin microstructure and engraftment failure. Given these limitations, new technologies, based on advanced therapies and regenerative medicine, have been applied to develop skin substitutes with several pharmaceutical applications that include injectable cell suspensions, cell-spray devices, sheets or 3Dscaffolds for skin tissue regeneration and others. Clinical practice for skin injuries has evolved to incorporate these innovative applications to facilitate wound healing, improve the barrier function of the skin, prevent infections, manage pain and even to ameliorate long-term aesthetic results. In this article, we review current commercially available skin substitutes for clinical use, as well as the latest advances in biomedical and pharmaceutical applications used to design advanced therapies and medical products for wound healing and skin regeneration. We highlight the current progress in clinical trials for wound healing as well as the new technologies that are being developed and hold the potential to generate skin substitutes such as 3D bioprinting-based strategies.

Pore geometry influences growth and cell adhesion of infrapatellar mesenchymal stem cells in biofabricated 3D thermoplastic scaffolds useful for cartilage tissue engineering.

The most pressing need in cartilage tissue engineering (CTE) is the creation of a biomaterial capable to tailor the complex extracellular matrix of the tissue. Despite the standardized used of polycaprolactone (PCL) for osteochondral scaffolds, the pronounced stiffness mismatch between PCL scaffold and the tissue it replaces remarks the biomechanical incompatibility as main limitation. To overcome it, the present work was focused in the design and analysis of several geometries and pore sizes and how they affect cell adhesion and proliferation of infrapatellar fat pad-derived mesenchymal stem cells (IPFP-MSCs) loaded in biofabricated 3D thermoplastic scaffolds. A novel biomaterial for CTE, the 1,4-butanediol thermoplastic polyurethane (b-TPUe) together PCL were studied to compare their mechanical properties. Three different geometrical patterns were included: hexagonal (H), square (S), and, triangular (T); each one was printed with three different pore sizes (PS): 1, 1.5 and 2 mm. Results showed differences in cell adhesion, cell proliferation and mechanical properties depending on the geometry, porosity and type of biomaterial used. Finally, the microstructure of the two optimal geometries (T1.5 and T2) was deeply analyzed using multiaxial mechanical tests, with and without perimeters, µCT for microstructure analysis, DNA quantification and degradation assays. In conclusion, our results evidenced that IPFP-MSCs-loaded b-TPUe scaffolds had higher similarity with cartilage mechanics and T1.5 was the best adapted morphology for CTE.