3D bioprinted biomask for facial skin reconstruction

Abstract

Skin injury to the face remains one of the greatest challenges in wound care due to the varied contours and complex movement of the face. Current treatment strategies for extensive facial burns are limited to the use of autografts, allografts, and skin substitutes, and these often result in scarring, infection, and graft failure. Development of an effective treatment modality will greatly improve the quality of life and social integration of the affected individuals. In this proof of concept study, we developed a novel strategy, called “BioMask”, which is a customized bioengineered skin substitute combined with a wound dressing layer that snugly fits onto the facial wounds. To achieve this goal, three-dimensional (3D) bioprinting principle was used to fabricate the BioMask that could be customized by patients’ clinical images such as computed tomography (CT) data. Based on a face CT image, a wound dressing material and cell-laden hydrogels were precisely dispensed and placed in a layer-by-layer fashion by the control of air pressure and 3-axis stage. The resulted miniature BioMask consisted of three layers; a porous polyurethane (PU) layer, a keratinocyte-laden hydrogel layer, and a fibroblast-laden hydrogel layer. To validate this novel concept, the bioprinted BioMask was applied to a skin wound on a pre-fabricated face-shaped structure in mice. Through this in vivo study using the 3D BioMask, skin contraction and histological examination showed the regeneration of skin tissue, consisting of epidermis and dermis layers, on the complex facial wounds. Consequently, effective and rapid restoration of aesthetic and functional facial skin would be a significant improvement to the current issues a facial wound patient experience.

Overview of Current Advances in Extrusion Bioprinting for Skin Applications

“…Indeed, keratinocytes instruct fibroblasts to produce several tissue-forming factors, i.e., keratinocyte growth factor (KGF), fibroblast growth factor (FGF), IL-6, GM-CSF, hepatocyte growth factor (HGF), IL-6, IL-19, and PDGF-BB [ 64 , 65 ]. Nonetheless, merely eleven of the reviewed articles introduced fibroblasts and keratinocytes together in their models [ 22 , 23 , 24 , 31 , 32 , 66 ], and more importantly, only five of these works have successfully created vascularized, full-thickness skin substitutes [ 3 , 4 , 7 , 20 , 26 ].…”

“…Indeed, PRP supplies cells with the appropriate stimuli for the proliferation, migration, and ECM protein synthesis. PRP or merely fibrinogen has been used in bioink formulations as a single-component bioink [ 24 ] or mixed with other molecules, including but not limited to collagen [ 21 , 22 , 66 ], dECM [ 7 ], alginate [ 30 ], gelatin [ 20 , 23 , 43 ], and others [ 4 ].…”

“…Progress in automation was achieved by developing a multisyringe extrusion system, allowing the simultaneous extrusion of bioinks, crosslinkers, and stabilizers [ 73 ]. Moreover, a particular biomimetic approach using fibrinogen blended with gelatin and hyaluronic acid (HA) enabled the manufacturing of facial skin grafts customized using medical images [ 23 ]. Additional complexity was achieved by bioprinting skin equivalents, comprising not only dermis and epidermis but also the basal layer [ 41 ].…”

3D Bioprinting of the Sustained Drug Release Wound Dressing with Double-Crosslinked Hyaluronic-Acid-Based Hydrogels

“…Recently, three-dimensional (3D) bioprinting has been introduced in the area of wound repair or healing—in particular, for the treatment of large wounds [13]—because of its capability of constructing complex micro-architectures with cellular components [14,15,16,17] and patient-specific features, such as matching wound dimensions and the use of patient-originated cells, which avoid immune rejection [18,19].…”

“…HA is the main component of the epidermis and dermis in the skin and is an excellent moisturizer [25]. Studies have also shown that HA interacts with endothelial cell receptors (CD44) to increase cell proliferation and promote angiogenesis, enhance collagen deposition and increase re-epithelialization in skin regeneration [13,21,22,23,24,25,26]. Additionally, HA is rapidly turned over in the body by hyaluronidase, with half-lives ranging from hours to days.…”