Three-Dimensional Printing and Cell Therapy for Wound Repair

Abstract

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Keywords: 3D printing; biofabrication; skin tissue engineering; wound repair.

Zhilian Yue, PhD

Gordon G. Wallace, DSc, PhD

Figure 1.

Anatomy of the skin. Permission obtained from McGraw-Hill Education. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 2.

Schematic representation of an inkjet printer.

Figure 3.

A schematic representation of LIFT. LIFT, laser-induced forward transfer.

Figure 4.

A schematic representation of an extrusion printer.

Figure 5.

Construction of two designs of layer-by-layer printing of collagen, human dermal fibroblasts, and keratinocytes. (A) Illustrates the design containing 10 layers, with layer 2 consisting of collagen and embedded fibroblasts, and layer 8 containing keratinocytes. Obtained and modified from with permission from Elsevier. (B) Illustrates the method containing 2 top layers containing keratinocytes and 3 layers of fibroblasts distributed equally in the bottom 11 layers. Obtained and modified from Lee et al. with permission from Mary Ann Liebert. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 6.

The visual appearance of a bioprinted graft in an immunodeficient mouse is shown in (A) and (B) shows a typical haematoxylin and eosin (H/E)-stained sample of the bioprinted human skin grafts in immunodeficient mice and (C) shows a typical H/E-stained sample of native human skin, with the white line indicating the dermo-epidermal junction (scale bar: 100 lm). Obtained and modified from Cubo et al. with permission from IOP Publishing. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound