3D bioprinting for fabricating artificial skin tissue

https://doi.org/10.1016/j.colsurfb.2021.112041Get rights and content

Highlights

  • Describing the manufacturing methods of tissue engineered skin.

  • Analyzing the advantages and disadvantages of main 3D bioprinting strategies.

  • Providing the status of bioprinted skin.

  • Discussing the challenges and future prospects of bioprinted skin.

Abstract

As an organ in direct contact with the external environment, the skin is the first line of defense against external stimuli, so it is the most vulnerable to damage. In addition, there is an increasing demand for artificial skin in the fields of drug testing, disease research and cosmetic testing. Traditional skin tissue engineering has made encouraging progress after years of development. However, due to the complexity of the skin structures, there is still a big gap between existing artificial skin and natural skin in terms of function. Three-dimensional (3D) bioprinting is an advanced biological manufacturing method. It accurately deposits bioinks into pre-designed three-dimensional shapes to create complex biological tissues. This technology aims to print artificial tissues and organs with biological activities and complete physiological functions, thereby alleviating the problem of tissues and organs in short supply. Here, based on the introduction to skin structure and function, we systematically elaborate and analyze skin manufacturing methods, 3D bioprinting biomaterials and strategies, etc. Finally, the challenges and perspectives in 3D bioprinting skin field are summarized.

Introduction

The skin has many important functions, such as preventing external damage, regulating body temperature and resisting harmful bacteria [1,2]. Skin damages due to trauma, burns and skin diseases are common in daily life [3,4]. Although the skin has a relatively high regeneration capacity, the skin appendages can hardly be regenerated under natural conditions. Especially for large-scale skin defects caused by accidents, if they are not treated in a timely and effective manner, a large amount of body fluids will be lost, which will seriously threaten the lives of patients [5,6]. Used treatment strategies mainly include autograft, allograft and xenograft [7]. Autogenous skin graft is a primary treatment method to recover the skin defect. However, the technology is limited by the shortage of donor sites and additional pain. Allogeneic and xenogeneic skin grafts are also unable to repair large-scale skin damage due to the limited number of donors [8]. At the same time, these technologies also face the risk of immune rejection [9]. In addition to repairing damaged skin, functional artificial skin is also used in other crucial fields, such as drug development and screening, research on disease mechanisms, and testing of cosmetic properties [[10], [11], [12]]. Although skin tissue engineering has made breakthroughs in the fabrication and application of artificial skin, there are still limitations, such as simple tissue structure, lack of skin functional units (glands, sensory neurons, hair follicles, etc.) and poor structural controllability. Therefore, there is an urgent need to develop new methods for artificial skin.

3D printing, also known as additive manufacturing, is a digital manufacturing technology that fabricates components layer by layer according to a specific path [13,14]. As an important branch of 3D printing technology, the core idea of 3D bioprinting is to realize the controllable spatial distribution of biological materials, cells and other active substances to fabricate tissues/organs with highly bionic structures and components [15,16]. This technology has the characteristics of strong controllability, short production cycle and individual customization, which provides unprecedented possibilities for manufacturing skin tissues with multiple layers of complex structures.

In this review, we describe the structure and function of human skin and present the recent developments in 3D bioprinted skin. We further highlight the process, bioinks selection and main types of 3D bioprinting. We finally provide the main challenges, future needs and some suggestions in fabricating skin.

Section snippets

Skin: structure and function

To manufacture tissue-engineered skin substitutes, we must have a full understanding of the internal structures, compositions and role of each part. Skin is a complex flat tissue, which is composed of three layers: epidermis, dermis and hypodermis from the outside to the inside [17]. The epidermis mainly consists of keratinocytes, which form keratinized stratified squamous epithelium [18]. Keratinocytes prevent pathogens, heat and ultraviolet radiation from damaging the skin environment. The

Skin manufacturing technologies

Tissue engineering was first proposed by the National Academy of Sciences Foundation. It is an interdisciplinary subject that uses the principles and methods of engineering and life sciences to research and develop biologically active tissue substitutes to achieve the repair and regeneration of damaged tissues and organs in the human body. With the development of tissue engineering research, its scope continues to expand. Substantial progress has been made in the research fields of tissue and

Discussion and perspectives

Regenerative medicine and tissue engineering based on 3D bioprinting have become one of the most active development directions in the interdisciplinary field of medicine and engineering. Specifically, for the present review topic on 3D bioprinting artificial skin, why choose 3D bioprinting to fabricate artificial skin? The key factor is a huge demand for the market and function of skin substitutes. In particular, the European Union has banned cosmetic testing on animals, so skin alternative

Conclusions

3D bioprinting is a biomanufacturing technology that allows printing cell-laden biomaterials to produce functional tissue. Bioprinted skin uses cells (keratinocytes, fibroblasts, melanocytes, mesenchymal stem cells, adipose stem cells, etc.), biomaterials and other active factors to develop multilayer skin substitutes in a controlled manner. However, the current bioprinting methods have technical challenges, such as cells deposition, biomaterials selection, vascular network refinement, and skin

Declaration of Competing Interest

The authors declare no conflicts of interest.

Acknowledgements

This work was supported by the grants from the National Natural Science Foundation of China (No. 61973206, 61703265, 61803250, 61933008), Shanghai Science and Technology Committee Sailing Program Foundation No. 17YF1406100, 17YF1406200 and Shanghai Science and Technology Committee Rising-Star Program No. 19QA1403700.

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