Tissue Engineered Skin and Wound Healing: Current Strategies and Future Directions

Abstract

The global volume of skin damage or injuries has major healthcare implications and, accounts for about half of the world's annual expenditure in the healthcare sector. In the last two decades, tissue-engineered skin constructs have shown great promise in the treatment of various skin-related disorders such as deep burns and wounds. The treatment methods for skin replacement and repair have evolved from utilization of autologous epidermal sheets to more complex bilayered cutaneous tissue engineered skin substitutes. However, inadequate vascularization, lack of flexibility in drug/growth factors loading and inability to reconstitute skin appendages such as hair follicles limits their utilization for restoration of normal skin anatomy on a routine basis. Recent advancements in cutting-edge technology from stem cell biology, nanotechnology, and various vascularization strategies have provided a tremendous springboard for researchers in developing and manipulating tissue engineered skin substitutes for improved skin regeneration and wound healing. This review summarizes the overview of skin tissue engineering and wound healing. Herein, developments and challenges of various available biomaterials, cell sources and in vitro skin models (full thickness and wound healing models) in tissue-engineered skin research are discussed. Furthermore, central to the discussion is the inclusion of various innovative strategies starting from stem cells, nanotechnology, vascularization strategies, microfluidics to three dimensional (3D) bioprinting based strategies for generation of complex skin mimics. The review then moves on to highlight the future prospects of advanced construction strategies of these bioengineered skin constructs and their contribution to wound healing and skin regeneration on current practice.

Extracellular matrix‐based scaffolding technologies for periodontal and peri‐implant soft tissue regeneration

“…66 Additionally, the manufacturing T A B L E 1 Summary of the extracellular matrix-based scaffolds used in periodontal and peri-implant soft tissue reconstruction SORT, strength-of-recommendation taxonomy; SORT A, consistent, good-quality patient-oriented evidence; SORT B, inconsistent or limited-quality patient-oriented evidence; SORT-C, consensus, disease-oriented evidence, usual practice, expert opinion or case series for studies of diagnosis, treatment, prevention, or screening. 67,68 Collagen is the most abundant naturally-derived protein in the human body and it's the major protein of the ECM of the skin dermal layer. Natural polymers were among the first biomaterials investigated in dental tissue engineering and, among their main advantages, a greater biocompatibility and interaction with host cells compared with synthetic matrices have been described.…”

“…74 methods of natural and synthetic biomaterials include many processes, such as electrospinning, 3D printing, or the use of CAD/CAM. 67 Several collagen-based grafts have been proposed in wound healing and tissue engineering of skin, including ADM, cellular epidermis/dermis, and bilayered skin equivalents. 66 Because of its properties of promoting wound healing, silk has been widely used as a scaffold in soft and bone tissue engineering in combination with epidermal or mesenchymal stem cells or fibroblasts.…”

“…Natural polymers were among the first biomaterials investigated in dental tissue engineering and, among their main advantages, a greater biocompatibility and interaction with host cells compared with synthetic matrices have been described. 67 The lack of biostability and frequent wound contracture are among the disadvantages of collagenbased scaffolds. 67,68 Collagen is the most abundant naturally-derived protein in the human body and it's the major protein of the ECM of the skin dermal layer.…”

“…67,68 Collagen is the most abundant naturally-derived protein in the human body and it's the major protein of the ECM of the skin dermal layer. 67,69 Synthetic materials have progressively become widely used in the biomedical field since they can be tailored for attaining different desired characteristics using various fabrication techniques. 67 The lack of biostability and frequent wound contracture are among the disadvantages of collagenbased scaffolds.…”

“…67 Several collagen-based grafts have been proposed in wound healing and tissue engineering of skin, including ADM, cellular epidermis/dermis, and bilayered skin equivalents. 66,67 Compared with natural polymers, synthetic scaffolds are produced in large quantities and have a longer shelf life. 67 These limitations have been overcome by cross-linking the collagen matrices or by combining them with other ECM molecules.…”