Significant progress has been made over the past 25 years in the development of in vitro -engineered substitutes that mimic human skin, either to be used as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. In this sense, laboratory-grown skin substitutes containing dermal and epidermal components offer a promising approach to skin engineering. In particular, a human plasma-based bilayered skin generated by our group, has been applied successfully to treat burns as well as traumatic and surgical wounds in a large number of patients in Spain. There are some aspects requiring improvements in the production process of this skin; for example, the relatively long time (three weeks) needed to produce the surface required to cover an extensive burn or a large wound, and the necessity to automatize and standardize a process currently performed manually. 3D bioprinting has emerged as a flexible tool in regenerative medicine and it provides a platform to address these challenges. In the present study, we have used this technique to print a human bilayered skin using bioinks containing human plasma as well as primary human fibroblasts and keratinocytes that were obtained from skin biopsies. We were able to generate 100 cm ² , a standard P100 tissue culture plate, of printed skin in less than 35 min (including the 30 min required for fibrin gelation). We have analysed the structure and function of the printed skin using histological and immunohistochemical methods, both in 3D in vitro cultures and after long-term transplantation to immunodeficient mice. In both cases, the generated skin was very similar to human skin and, furthermore, it was indistinguishable from bilayered dermo-epidermal equivalents, handmade in our laboratories. These results demonstrate that 3D bioprinting is a suitable technology to generate bioengineered skin for therapeutical and industrial applications in an automatized manner.

Skin wound healing is known to be impaired in space. As skin is the tissue mostly at risk to become injured during manned space missions, there is the need for a better understanding of the biological mechanisms behind the reduced wound healing capacity in space. In addition, for far-distant and long-term manned space missions like the exploration of Mars or other extraterrestrial human settlements, e.g., on the Moon, new effective treatment options for severe skin injuries have to be developed. However, these need to be compatible with the limitations concerning the availability of devices and materials present in space missions. Three-dimensional (3D) bioprinting (BP) might become a solution for both demands, as it allows the manufacturing of multicellular, complex and 3D tissue constructs, which can serve as models in basic research as well as transplantable skin grafts. The perspective article provides an overview of the state of the art of skin BP and approach to establish this additive manufacturing technology in space. In addition, the several advantages of BP for utilization in future manned space missions are highlighted.

Fifty years after the first human landed on the Moon mankind has started to plan next steps for manned space exploration missions. The international space agencies have begun to investigate the requirements for both a human settlement on the Moon and manned missions to Mars. For such activities significantly improved medical treatment facilities on-board the spacecrafts or within the extraterrestrial settlements need to be provided as no fast return opportunities to Earth would exist anymore in case of severe trauma or illness. Bioprinting is believed to play a significant role as it could offer the possibilities to produce patient-specific tissue constructs in a semi-automated manner. Therefore, both the space agencies and the bioprinting community have started to study possible applications of bioprinting technologies in space. Besides utilisation of bioprinted tissue constructs for the treatment of injured astronauts bioprinting will become relevant for the fabrication of three-dimensional tissue models for basic research, e.g. concerning effects of microgravity and cosmic radiation on cells and tissues. This perspective article describes the current state of the art including medical scenarios for new far-distant space exploration missions, first approaches towards establishment of bioprinters in space and which limitations have to be resolved to use bioprinting under the specific conditions of space flight like altered gravity conditions.

Additive manufacturing (AM) techniques are becoming the approaches of choice for the construction of scaffolds in tissue engineering. However, the development of 3D printing in this field brings unique challenges, which must be accounted for in the design of experiments. The common printing process parameters must be considered as important factors in the design and quality of final 3D-printed products. In this work, we study the influence of some parameters in the design and fabrication of PCL scaffolds, such as the number and orientation of layers, but also others of “hidden” importance, such as the cooling down rate while printing, or the position of the starting point in each layer. These factors can have an important impact oin the final porosity and mechanical performance of the scaffolds. A pure polycaprolactone filament was used. Three different configurations were selected for the design of the internal structure of the scaffolds: a solid one with alternate layers (solid) (0°, 90°), a porous one with 30% infill and alternate layers (ALT) (0°, 90°) and a non-alternated configuration consisting in printing three piled layers before changing the orientation (n-ALT) (0°, 0°, 0°, 90°, 90°, 90°). The nozzle temperature was set to 172 °C for printing and the build plate to 40 °C. Strand diameters of 361 ± 26 µm for room temperature cooling down and of 290 ± 30 µm for forced cooling down, were obtained. A compression elastic modulus of 2.12 ± 0.31 MPa for n-ALT and 8.58 ± 0.14 MPa for ALT scaffolds were obtained. The cooling down rate has been observed as an important parameter for the final characteristics of the scaffold.