India's first bioprinted human skin

Using a bioink laden with cells, Indian researchers have been able to print, for the first time, three-dimensional skin models just like human skin¹. The models, shaped in a 3D printer, mimic the exact structure and function of human skin and could be useful in testing the efficacy of bioactive molecules, drugs and cosmetic products.

Through a process called bioprinting, the researchers at the Indian Institute of Delhi (IITD) laid out certain skin-forming cells in layers inside the constructs. “This could reduce or replace the use of animals in testing drugs that can’t be tested on human skin isolated from a dead body,” says lead researcher Sourabh Ghosh from IITD.

In the past two decades, scientists have been trying to develop skin constructs by culturing various cells on a collagen gel or on porous scaffolds. But none of those has been able to replicate the complex anatomical features of human skin, such as the undulated shape at the interface of dermis, the inner skin layer, and epidermis, the outer skin layer.

In search of an alternative and efficient skin model, Ghosh and his colleagues, teaming up with researchers from the ITC Life Sciences and Technology Centre in Bangalore, prepared a bioink by mixing a silk protein with gelatin. They then blended specific skin-forming cells with the bioink.

Next, they used the cell-laded bioink to print three-dimensional cell-containing skin constructs using a computer-aided model of human skin.

Each skin construct contained cell-embedded layers of dermis and epidermis. When cultured in nutrient broths, the cells in the constructs thrived for up to three weeks. Among the cells, fibroblasts and keratinocytes, two key skin-forming cells uniformly distributed themselves throughout the constructs and remodelled their surrounding matrix. The fibroblast cells even changed their shape from round to spindle.

After a week, keratinocytes proliferated and migrated out of the constructs. By three weeks, these cells moved towards the constructs’ pores, gradually almost covering them. Besides growth and migration, the cells expressed genes and secreted proteins specific to human skin. The researchers identified the activity of specific genes that play vital roles in wound healing and skin remodeling processes in the human skin.

The construct also exhibited the undulating feature that is usually found at the interface of the dermis and epidermis layers of the skin.

“The skin constructs are a step forward in recapitulating the structures and functions of various skin cells, which may aid testing of specific molecules that affect skin functions,” says Biman B. Mandal, a materials scientist from the Indian Institute of Technology in Guwahati, India, who is not involved in this research.

Pratyoosh Shukla, a biotechnologist from the Maharshi Dayanand University in Haryana, India, thinks that the skin constructs are promising. The technique, Shukla says, is quite handy and effective and can primarily help avoid animal-based testing of bioactive chemicals or drugs.

However, prior to probing their industrial usefulness, the constructs’ specificity and sensitivity need to be explored, he adds.

Encouraged by the preliminary results, Ghosh and his team are planning the next step, in which they want to fine-tune the skin constructs further for simulating a few diseased-skin conditions.

References

1. Admane, P. et al. Direct 3D bioprinted full-thickness skin constructs recapitulate regulatory signaling pathways and physiology of human skin. Bioprinting. 15, e00051 (2019)