Skin bioprinting: a novel approach for creating artificial skin from synthetic and natural building blocks

Abstract

Significant progress has been made over the past few decades in the development of in vitro-engineered substitutes that mimic human skin, either as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. Tissue engineering has been developing as a novel strategy by employing the recent advances in various fields such as polymer engineering, bioengineering, stem cell research and nanomedicine. Recently, an advancement of 3D printing technology referred as bioprinting was exploited to make cell loaded scaffolds to produce constructs which are more matching with the native tissue. Bioprinting facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissue-engineering approaches. Bioprinted skin substitutes or equivalents containing dermal and epidermal components offer a promising approach in skin bioengineering. Various materials including synthetic and natural biopolymers and cells with or without signalling molecules like growth factors are being utilized to produce functional skin constructs. This technology emerging as a novel strategy to overcome the current bottle-necks in skin tissue engineering such as poor vascularization, absence of hair follicles and sweat glands in the construct.

Beyond 2D: 3D bioprinting for skin regeneration

“…Although many biomaterials are widely used in tissue engineering, such as PLA and PCL, cell compatibility is essential for the selection of bioink for cell encapsulation and bioprinting . For instance, PLA with a relatively high processing (melting) temperature is not suitable for bioprinting . Based on this and previous studies, hydrogels; natural biopolymers such as alginate, chitosan, gelatin, etc …”

“…Because there is no direct force applied to the cells, laser‐assisted bioprinter supports high cell viabilities. It is characterised by excellent resolution, but the cost of laser sources is a little high …”

“…13 Recently, because of the ability of self-renewal and differentiation, a variety of stem cells is widely used in printing skin substitutes. 6,14,15 Amniotic fluid-derived stem cells (AFSCs) are widely pluripotent and have been identified to differentiate into all three lineages' cells. 6,14,15 They were used to bioprint on skin wounds in mice directly because of their immunocompetency.…”

“…5 For example, 3D-printed extracellular matrix (ECM) facilitates the simultaneous and highly specific deposition of multiple types of skin cells and biomaterials, a process that is lacking in conventional skin tissueengineering approaches. 6 In addition, a 3D-ECM created by our group using 3D bioprinting technology can successfully achieve specific cell differentiation in vitro and functional skin and its appendages regeneration in vivo. 3 Therefore, bioprinting offers potential advantages for skin regeneration and might be a revolutionary strategy.…”

3D bioprinted biomask for facial skin reconstruction

“…When synthetic biomaterials are used, they should be non-toxic, non-immunogenic, and non-inflammatory and eventually degrade [10, 11]. Very recently, threedimensional (3D) bioprinting strategies have been introduced in the skin tissue engineering because of their capability to produce complex micro-architectures with cellular components [12–15]. Patient-specific bioengineered tissue constructs can also be prepared by 3D bioprinting a fabrication code obtained from the patient’s CT data [16].…”