Table 5.

Skin biofabrication using EBB

Authors	Methodology	Major Findings	Limitations
Skardal et al., 2012	• Cell-laden composite bioinks (fibrin and collagen), encapsulating amniotic-fluid stem cells (AFSCs) and BM-MSCs, were bioprinted, implanted over a murine mid-dorsal skin defect model, and assessed based on wound closure rate at 0, 7, and 14 days post-surgery	• Wound closure, contraction, and re-epithelialization of the defect site was accelerated in implanted cellular constructs when compared to acellular constructs  • Robust microvessel integration into the implanted construct was enhanced, primarily due to AFSC cytokine secretion	• Lack of cell integration from the implant to the wound bed indicates that tissue-engineered implants possess limited engraftment potential, compromising their long-term stability
Lee et al., 2014	• Fibroblast-laden collagen constructs were 3D-bioprinted and keratinized to recapitulate the native structure of the epidermal-dermal junction  • Bioengineered construct were cultured with the fabricated dermis submerged in media and the epidermal layer at the air-liquid interface	• Bioengineered constructs resembled the morphological appearance and biological structure of native skin tissue in vitro	• Methods do not fully recapitulate the architectural complexity of skin, which requires the presence of hair follicles, pigment cells, sweat glands, blood vessels, and sensory neurons
Pourchet et al., 2017	•Fibroblasts-laden composite bioinks (alginate, gelatin, and fibrinogen) were printed and cured onto a cooling plate to emulate dermal tissue, keratinized to mimic epidermal tissue, and conditioned for 26 days	• Bioengineered constructs exhibited comparable morphological and biological features as native skin tissue, with defined epidermal stratification and dermal tissue maturation within 3 weeks	• Vascularization of bioprinted skin flaps are required to maintain stable and functional tissue throughput the lifetime of the recipient  •Studies lack information on the integrative potential (both vasculature and dermal tissue) of bioprinted skin in an in vivo defect model
Kim et al., 2018	• Biomimetic scaffolds of native skin were printed using EBB, to fabricate the dermis (fibroblastladen S-dECM), and inkjet bioprinting, to fabricate the epidermi, (keratinocyte-laden culture medium)  • Constructs were cultured until stratification and keratinization were achieved  • EPC/ASC-laden S-dECM were printed and pre-vascularized prior to implantation in a cutaneous wound healing murine model	•S-dECM maintained its endogenous biophysical and biomolecular features, and can serve as a bioink  • EBB can print prevascularized S-dECM to promote wound healing in vivo  • Co-encapsulation EPCs and ASCs in S-dECM bioink support rapid wound closure, re-epithelialization, and neovascularization of a full-thickness excisional wound	• Biofabrication of functional skin for full-thickness defects will require the presence of tissue-engineered subcutaneous fat to replenish the hypodermis