Bioprinting technologies are powerful additive biofabrication techniques to produce cellular constructs for skin tissue engineering owing to their unique ability to precisely pattern living and non-living materials in predefined spatial locations. This unique feature, combined with the computer controlled printing and medical imaging techniques, enable researchers and clinicians to generate patient specific constructs partly replicating the intricate compositional and architectural organization of the skin. Bioprinting has been used to automatically dispense hydrogels with skin cells located in prescribed sites that promote skin formation in vitro and in vivo. Current skin bioprinting approaches mostly rely on the sequential printing of fibroblasts and keratinocytes embedded within a homogeneous hydrogel. Although such approaches have already been translated to pre-clinical scenarios, they still present limitations in terms of fully replicating the cellular and extracellular matrix (ECM) heterogeneity in native skin. The success of bioprinting for skin repair strongly depends on the design of printable bioinks capable of supporting the function of printed cells and stimulating the production of new ECM components. To better mimic the human skin, novel developments in dedicated bioprinting technologies, in the design of bioinks, as well as in the printing of vascularised constructs are necessary. This paper presents an overview regarding the use of bioprinting for skin tissue engineering applications. The operating principles of bioprinting technologies are outlined along with requirements of printed skin constructs. Finally, preclinical results are summarized and future perspectives for the field are highlighted.

Polycaprolactone (PCL) is widely used in tissue engineering due to its interesting properties, namely biocompatibility, biodegradability, elastic nature, availability, cost efficacy, and the approval of health authorities such as the American Food and Drug Administration (FDA). The PCL degradation rate is not the most adequate for specific applications such as skin regeneration due to the hydrophobic nature of bulk PCL. However, PCL electrospun fiber meshes, due to their low diameters resulting in high surface area, are expected to exhibit a fast degradation rate. In this work, in vitro and in vivo degradation studies were performed over 90 days to evaluate the potential of electrospun PCL as a wound dressing. Enzymatic and hydrolytic degradation studies in vitro, performed in a static medium, demonstrated the influence of lipase, which promoted a rate of degradation of 97% for PCL meshes. In an in vivo scenario, the degradation was slower, although the samples were not rejected, and were well-integrated in the surrounding tissues inside the subcutaneous pockets specifically created.

In situ cross-linked hydrogels have the advantage of effectively fulfilling the wound in its shape and depth. Amongst the new generation of natural-based biopolymers being proposed for wound care and skin regeneration, silk sericin is particularly interesting due to its exceptional properties such as biocompatibility, biodegradability, and antioxidant behavior, among others. In this study, a new enzyme-mediated cross-linked hydrogel composed of silk sericin is proposed for the first time. The developed hydrogel cross-linking strategy was performed via horseradish peroxidase, under physiological conditions, and presented gelling kinetics under 3 min, as demonstrated by its rheological behavior. The hydrogels presented a high degree of transparency, mainly due to their amorphous conformation. Degradation studies revealed that the hydrogels were stable in phosphate buffer solution (PBS) (pH 7.4) for 17 days, while in the presence of protease XIV (3.5 U/mg) and under acute and chronic physiological pH values, the stability decreased to 7 and 4 days, respectively. During protease degradation, the present sericin hydrogels demonstrated antioxidant activity. In vitro studies using an L929 fibroblast cell line demonstrated that these hydrogels were noncytotoxic, promoting cell adhesion and massive cell colonization after 7 days of culture, demonstrating that cells maintained their viability and proliferation. In addition, the application of sericin-based hydrogel in an in vivo diabetic wound model validated the feasibility of the in situ methodology and demonstrated a local anti-inflammatory effect, promoting the healing process. This study presents a simple, fast, and practical in situ approach to produce a sericin-based hydrogel able to be applied in low exudative chronic wounds. Moreover, the study herein reported fosters the valorization of a textile industrial by-product by its integration in the biomedical field.