3D Cell Printing of Perfusable Vascularized Human Skin Equivalent Composed of Epidermis, Dermis, and Hypodermis for Better Structural Recapitulation of Native Skin

Abstract

Although skin cell‐printing has exhibited promises for fabrication of functional skin equivalents, existing skin models through 3D cell printing are still composed of dermal and epidermal layers. However, a key hope for printing skin is to improve structural complexity of human skin over conventional construction, enabling the precise localization of multiple cell types and biomaterials. Here, the complexity of skin anatomy is increased using 3D cell printing. A novel printing platform is suggested for engineering a matured perfusable vascularized 3D human skin equivalent composed of epidermis, dermis, and hypodermis. The skin model is evaluated using functional markers representing each region of epidermis, dermis, and hypodermis to confirm tissue maturation. It is hypothesized that the vascularized dermal and hypodermal compartments that provide a more realistic microenvironment can promote cross‐talks with the epidermal compartment, producing better recapitulation of epidermal morphogenesis. Skin stemness in epithelial tissue is investigated. These findings reveal that the full‐thickness skin has more similarities to the native human skin compared with the dermal and epidermal skin model, indicating that it better reflects the actual complexity of native human skin. It is envisioned that it offers better predictive and reliable in vitro platform for investigation of mechanisms of pathological research and skin disease modeling.

Three Dimensional Bioprinting of a Vascularized and Perfusable Skin Graft Using Human Keratinocytes, Fibroblasts, Pericytes, and Endothelial Cells

“…40,41 Furthermore, we were able to demonstrate that our approach overcomes limitations related to vessel regression in vitro and perfusion in vivo. 26,42 Specifically, the incorporation of FBs and PCs mitigated vessel regression before engraftment, and the vessels were perfused in vivo both in an angiocrine manner (as evidenced by host vessel invasion) and through anastomosis (as evidenced by preinjected Ulex staining).…”

Hydrogel-Based Technologies for the Diagnosis of Skin Pathology

“…Skin properties of individual patient can somewhat differ from other patients bearing the same disease [59]. To this end, biofabrication (i.e., 3D bioprinting and electrospinning) of in vitro skin models employing patient-isolated cells provides a better avenue to recapitulate the physio-/pathophysiology of human skin in a personalized manner [161]. Coupled with perfusable vasculature and inclusion of skin appendages and immune-competent cells, these skin constructs allow reliable and robust skin disease modeling (e.g., AD) [162,163].…”

3D Bioprinting Strategies for the Regeneration of Functional Tubular Tissues and Organs

“…It has an inherent component of tissue-specific microenvironment cues, such as proteoglycans, glycoprotein, and collagenous protein. To date, various dECM-based inks have been reported for target-specific tissues, such as derived skin [ 80 ], bone [ 39 ], vessel [ 59 ], liver [ 81 ], kidney [ 82 ], and so on. Each derived tissue has different printability properties, but all have the distinguishing feature of temperature-responsive gelation under the physiological environment [ 83 ].…”