A team of researchers has recreated human-like skin pigmentation using 3D bioprinting to control the distribution of melanin-producing skin cells on a biomimetic tissue substrate. The bioprinting method was developed during a study by the Singapore Centre for 3D Printing (SC3DP) and the Singapore Institute of Manufacturing Technology (SIMTech). The new technique has the potential to produce pigment-correct skin grafts.

Natural looking pigmentation for skin grafts would address many of the issues with current engineered skin constructs. Patients are often negatively perceive their own image after receiving grafted uniform skin which can lack complex features such as pigmentation, hair follicles and sweat glands.

Lead author of the study, Wei Long Ng, said: “3D bioprinting is an excellent platform for the precise deposition of biomaterials and living cells to make biomimetic skin, in large volumes with great repeatability. However, non-uniform skin pigmentation is often seen, and this remains a huge challenge to be solved.”

“Our aim with this project was to use this method to demonstrate the feasibility of making 3D in-vitro pigmented human skin constructs, with uniform skin pigmentation.”

To make the 3D pigmented skin, the team collected three different types of epidermal skin cells: keratinocytes, melanocytes and fibroblasts. They then used a bioprinting method described as a two-step ‘drop on demand’. This technique involves fabricating hierarchical porous collagen-based structures that closely resemble the skin’s dermal area. Then the collected epidermal skin cells are deposited at pre-defined positions on top of the biomimetic dermal skin constructs, which helps to create a 3D pigmented appearance on the constructed tissue.

Dr Long Ng added: “When we compared the 3D printed skin constructs to those made using a manual-casting method, we found two distinct differences between the two fabrication approaches – the cell distribution on top of the dermal regions, and the microstructures within the dermal regions. The two-step bioprinting strategy enables the standardised distribution of printed cells in a highly-controlled way, as compared to the manual casting approach.

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“Furthermore, the bioprinting technique allows the manipulation of pore sizes within the 3D collagen-fibroblast matrices, to fabricate hierarchical porous structures that are clearly seen in the native skin tissues. In contrast, tuning the skin microstructure within the 3D collagen-fibroblast matrices using the manual-casting approach is extremely challenging.”

The method could also be used to construct skin for toxicology testing and fundamental cell research.