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The aim of this review is to present 3D bioprinting of skin substitutes as an efficient approach of managing skin injuries. From a clinical point of view, classic treatments only provide physical protection from the environment, and existing engineered scaffolds, albeit acting as a physical support for cells, fail to overcome needs, such as neovascularisation. In the present work, the basic principles of bioprinting, together with the most popular approaches and choices of biomaterials for 3D-printed skin construct production, are explained, as well as the main advantages over other production methods. Moreover, the development of this technology is described in a chronological manner through examples of relevant experimental work in the last two decades: from the pioneers Lee et al. to the latest advances and different innovative strategies carried out lately to overcome the well-known challenges in tissue engineering of skin. In general, this technology has a huge potential to offer, although a multidisciplinary effort is required to optimise designs, biomaterials and production processes.

In the current study, we developed a novel gelatin-based bilayer wound dressing. We used different crosslinking agents to confer unique properties to each layer, obtaining a bioinspired multifunctional hydrofilm suitable for wound healing. First, we produced a resistant and non-degradable upper layer by lactose-mediated crosslinking of gelatin, which provided mechanical support and protection to overall design. For the lower layer, we crosslinked gelatin with citric acid, resulting in a porous matrix with a great swelling ability. In addition, we incorporated chitosan into the lower layer to harness its wound healing ability. FTIR and SEM analyses showed that lactose addition changed the secondary structure of gelatin, leading to a more compact and smoother structure than that obtained with citric acid. The hydrofilm was able to swell 384.2 ± 57.2% of its dry weight while maintaining mechanical integrity. Besides, its water vapour transmission rate was in the range of commercial dressings (1381.5 ± 108.6 g/m2·day). In vitro, cytotoxicity assays revealed excellent biocompatibility. Finally, the hydrofilm was analysed through an ex vivo wound healing assay in human skin. It achieved similar results to the control in terms of biocompatibility and wound healing, showing suitable characteristics to be used as a wound dressing.

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