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Review
. 2021 Feb 18;19(1):83.
doi: 10.1186/s12967-021-02752-2.

Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration

Qian Hua Phua  1 , Hua Alexander Han  1 , Boon-Seng Soh  2   3
Affiliations
Review

Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration

Qian Hua Phua et al. J Transl Med. .

Abstract

The skin is made up of a plethora of cells arranged in multiple layers with complex and intricate vascular networks, creating a dynamic microenvironment of cells-to-matrix interactions. With limited donor sites, engineered skin substitute has been in high demand for many therapeutic purposes. Over the years, remarkable progress has occurred in the skin tissue-engineering field to develop skin grafts highly similar to native tissue. However, the major hurdle to successful engraftment is the incorporation of functional vasculature to provide essential nutrients and oxygen supply to the embedded cells. Limitations of traditional tissue engineering have driven the rapid development of vascularized skin tissue production, leading to new technologies such as 3D bioprinting, nano-fabrication and micro-patterning using hydrogel based-scaffold. In particular, the key hope to bioprinting would be the generation of interconnected functional vessels, coupled with the addition of specific cell types to mimic the biological and architectural complexity of the native skin environment. Additionally, stem cells have been gaining interest due to their highly regenerative potential and participation in wound healing. This review briefly summarizes the current cell therapies used in skin regeneration with a focus on the importance of vascularization and recent progress in 3D fabrication approaches to generate vascularized network in the skin tissue graft.

Keywords: 3D bioprinting; Engineered skin graft; Skin regeneration; Stem cells; Vascularization.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
A staged schematic of a traditional engineered skin graft implanted onto the injured skin. Autologous cells are first isolated from the patient’s biopsies and cultured to the desired confluency in vitro. The cells are then seeded onto a biocompatible scaffold in the presence of growth factors and cytokines that aid in the creation and maturation of a functional skin graft. The graft is subsequently implanted onto the wound area to aid in recovery and regeneration of the skin tissue
Fig. 2
Fig. 2
A schematic representation of the process of vasculogenesis and angiogenesis subsequent to the skin graft transplantation. In the early stages following transplantation, nutrients from the wound bed diffuse along a gradient into the graft via the process of plasmatic imbibition but is limited by the range of diffusion. Around 48 h after the transplantation, the vessels of the host tissue begin to form anastomoses with the vascular buds of the graft during inosculation. The inception of a functional vascular network between the graft and the recipient bed enhances the survivability of the graft. The process of revascularization occurs within 72 h whereby the ingrowth of new vessels from the recipient bed to the graft, accumulation of extracellular matrix and the subsequent maturation of the new vessels augments the stability of the engrafted tissue
Fig. 3
Fig. 3
A schematic representation of the 3D bioprinting of engineered skin tissue. Cells are isolated from the patient’s biopsy and cultured in vitro to reach sufficient numbers. Isolated fibroblasts can also be re-programmed into iPSCs, which can subsequently be differentiated into the desired cell types and amounts within a shorter period of time. Bio-inks usually comprise of live cells encapsulated by a biopolymer material which acts as a scaffold. Using 3D technology, skin tissues are bio-printed in a conformationally defined manner and allowed to mature before implanting the tissue onto the patient
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