The Importance of Mimicking Dermal-Epidermal Junction for Skin Tissue Engineering: A Review

There is a distinct boundary between the dermis and epidermis in the human skin called the basement membrane, a dense collagen network that creates undulations of the dermal–epidermal junction (DEJ). The DEJ plays multiple roles in skin homeostasis and function, namely, enhancing the adhesion and physical interlock of the layers, creating niches for epidermal stem cells, regulating the cellular microenvironment, and providing a physical boundary layer between fibroblasts and keratinocytes. However, the primary role of the DEJ has been determined as skin integrity; there are still aspects of it that are poorly investigated. Tissue engineering (TE) has evolved promising skin regeneration strategies and already developed TE scaffolds for clinical use. However, the currently available skin TE equivalents neglect to replicate the DEJ anatomical structures. The emergent ability to produce increasingly complex scaffolds for skin TE will enable the development of closer physical and physiological mimics to natural skin; it also allows researchers to study the DEJ effect on cell function. Few studies have created patterned substrates that could mimic the human DEJ to explore their significance. Here, we first review the DEJ roles and then critically discuss the TE strategies to create the DEJ undulating structure and their effects. New approaches in this field could be instrumental for improving bioengineered skin substitutes, creating 3D engineered skin, identifying pathological mechanisms, and producing and screening drugs.

Bioengineered Skin Substitutes: Advances and Future Trends

As the largest organ in the human body, the skin has the function of maintaining balance and protecting from external factors such as bacteria, chemicals, and temperature. If the wound does not heal in time after skin damage, it may cause infection or life-threatening complications. In particular, medical treatment of large skin defects caused by burns or trauma remains challenging. Therefore, human bioengineered skin substitutes represent an alternative approach to treat such injuries. Based on the chemical composition and scaffold material, skin substitutes can be classified into acellular or cellular grafts, as well as natural-based or synthetic skin substitutes. Further, they can be categorized as epidermal, dermal, and composite grafts, based on the skin component they contain. This review presents the common commercially available skin substitutes and their clinical use. Moreover, the choice of an appropriate hydrogel type to prepare cell-laden skin substitutes is discussed. Additionally, we present recent advances in the field of bioengineered human skin substitutes using three-dimensional (3D) bioprinting techniques. Finally, we discuss different skin substitute developments to meet different criteria for optimal wound healing.

Management of Soft Tissue Injuries in the Maxillofacial Region

Soft tissue injuries of head and neck are the most common injuries encountered by the maxillofacial surgeons during their clinical practice. Therefore, one must have a sound knowledge of the various types, their mechanisms of injuries and most importantly, the management of the same. This chapter discusses the classification system of all types of soft tissue injuries, and focuses on the principles of management of different types of the injuries, with emphasis on their mechanism and healing process. Numerous figures, box diagrams and case scenarios are added to make the chapter interesting and provide real time information about the topic. A special note on necrotizing fasciitis, one of the most challenging infections in the head and neck region has also been mentioned along with information about wound dressings. Recent advances in the management of soft tissue injuries like use of growth factors, bioengineered skin substitutes and stem cell therapy are enumerated for the readers to encourage them about futuristic approaches. The authors hope that the readership attains a holistic knowledge about various aspects of the soft tissue injuries and their management.

A bilayered skin substitute developed using eggshell membrane crosslinked gelatin-chitosan cryogel

Commercially available allografts and xenografts pose problems such as high cost, risk of infection transmission and immune rejection of grafts. Thus, bioengineered skin substitutes fabricated from natural biomaterials or synthetic...

Evaluating the Effect of Integra Seeded with Adipose Tissue-Derived Stem Cells or Fibroblasts in Wound Healing

Background: Extensive loss of skin in burn patients can have devastating consequences, both physically and mentally. Adipose-Derived Stem Cells (ADSCs) and fibroblasts are known to play significant roles in the process of wound healing. Recently, bioengineered skin has been considered for wound healing purposes. Methods: Investigate the effect of Integra seeded with ADSCs, fibroblasts, or both on wound healing. Results: We found that when Integra is seeded with ADSCs and fibroblasts, both types of cells incorporate and proliferate, the phenomenon becoming more robust when the cells are co-cultured on Integra, both in vitro and in vivo. In addition, when these cells are seeded on Integra, they stimulate epithelization with no signs of inflammation and skin necrosis being observed when transplanted on animals for 7 days. Conclusion: ADSCs and fibroblasts seeded on Integra could decrease the number of α-SMA positive myofibroblasts, leading to scarless wound healing. The evidence from this study is strongly supportive that Integra seeded with ADSCs and fibroblasts is an appropriate and effective bioengineered skin for wound healing.

Bioengineered Skin Substitutes: The Role of Extracellular Matrix and Vascularization in the Healing of Deep Wounds

The formation of severe scars still represents the result of the closure process of extended and deep skin wounds. To address this issue, different bioengineered skin substitutes have been developed but a general consensus regarding their effectiveness has not been achieved yet. It will be shown that bioengineered skin substitutes, although representing a valid alternative to autografting, induce skin cells in repairing the wound rather than guiding a regeneration process. Repaired skin differs from regenerated skin, showing high contracture, loss of sensitivity, impaired pigmentation and absence of cutaneous adnexa (i.e., hair follicles and sweat glands). This leads to significant mobility and aesthetic concerns, making the development of more effective bioengineered skin models a current need. The objective of this review is to determine the limitations of either commercially available or investigational bioengineered skin substitutes and how advanced skin tissue engineering strategies can be improved in order to completely restore skin functions after severe wounds.

Fabrication of Bioengineered Skin by Injection Molding: A Feasibility Study on Automation

The use of bioengineered skin has facilitated fundamental and applied research because it enables the investigation of complex interactions between various cell types as well as the extracellular matrix. The predominantly manual fabrication of these living tissues means, however, that their quality, standardization, and production volume are extremely dependent on the technician’s experience. Simple laboratory automation could facilitate the use of living tissues by a greater number of research groups. We developed and present here an injection molding technique for the fabrication of bilayered skin equivalents. The tissue was formed automatically by two separate injections into a customized mold to produce the dermal and epidermal skin layers. We demonstrated the biocompatibility of this fabrication process and confirmed the resulting bilayered morphology of the bioengineered skin using histology and immunohistochemistry. Our findings highlight the possibility of fabricating multilayered living tissue by injection molding, suggesting that further investigation into this automation method could result in the rapid and low-cost fabrication of standardized bioengineered skin.