Wound represents a significant socioeconomic burden for both affected individuals and as a whole healthcare system. Accordingly, stem cells have garnered attention due to their differentiation capacity and ability to aid tissue regeneration by releasing biologically active molecules, found in the cells’ cultivated medium which known as conditioned medium (CM) or secretomes. This acellular approach provides a huge advantage over conventional treatment options, which are mainly used cellular treatment at wound closure. Interestingly, the secretomes contained the cell-secreted proteins such as growth factors, cytokines, chemokines, extracellular matrix (ECM), and small molecules including metabolites, microvesicles, and exosomes. This review aims to provide a general view on secretomes and how it is proven to have great potential in accelerating wound healing. Utilizing the use of secretomes with its secreted proteins and suitable biomaterials for fabrications of acellular skin substitutes can be promising in treating skin loss and accelerate the healing process.
Skin tissue engineering has made remarkable progress in wound healing treatment with the advent of newer fabrication strategies using natural/synthetic polymers and stem cells. Stem cell therapy is used to treat a wide range of injuries and degenerative diseases of the skin. Nevertheless, many related studies demonstrated modest improvement in organ functions due to the low survival rate of transplanted cells at the targeted injured area. Thus, incorporating stem cells into biomaterial offer niches to transplanted stem cells, enhancing their delivery and therapeutic effects. Currently, through the skin tissue engineering approach, many attempts have employed biomaterials as a platform to improve the engraftment of implanted cells and facilitate the function of exogenous cells by mimicking the tissue microenvironment. This review aims to identify the limitations of stem cell therapy in wound healing treatment and potentially highlight how the use of various biomaterials can enhance the therapeutic efficiency of stem cells in tissue regeneration post-implantation. Moreover, the review discusses the combined effects of stem cells and biomaterials in in vitro and in vivo settings followed by identifying the key factors contributing to the treatment outcomes. Apart from stem cells and biomaterials, the role of growth factors and other cellular substitutes used in effective wound healing treatment has been mentioned. In conclusion, the synergistic effect of biomaterials and stem cells provided significant effectiveness in therapeutic outcomes mainly in wound healing improvement.
Skin plays an important role in defense against infection and other harmful biological agents. Due to its fragile structure, skin can be easily damaged by heat, chemicals, traumatic injuries and diseases. An autologous bilayered human skin equivalent, MyDerm™, was engineered to provide a living skin substitute to treat critical skin loss. However, one of the disadvantages of living skin substitute is its short shelf-life, hence limiting its distribution worldwide. The aim of this study was to evaluate the shelf-life of MyDerm™ through assessment of cell morphology, cell viability, population doubling time and functional gene expression levels before transplantation. Skin samples were digested with 0.6% Collagenase Type I followed by epithelial cells dissociation with TrypLE Select. Dermal fibroblasts and keratinocytes were culture-expanded to obtain sufficient cells for MyDerm™ construction. MyDerm™ was constructed with plasma-fibrin as temporary biomaterial and evaluated at 0, 24, 48 and 72 hours after storage at 4°C for its shelf-life determination. The morphology of skin cells derived from MyDerm™ remained unchanged across storage times. Cells harvested from MyDerm™ after storage appeared in good viability (90.5%±2.7% to 94.9%±1.6%) and had short population doubling time (58.4±8.7 to 76.9±19 hours). The modest drop in cell viability and increased in population doubling time at longer storage duration did not demonstrate a significant difference. Gene expression for CK10, CK14 and COL III were also comparable between different storage times. In conclusion, MyDerm™ can be stored in basal medium at 4°C for at least 72 hours before transplantation without compromising its functionality.
Skin substitutes can provide a temporary or permanent treatment option for chronic wounds. The selection of skin substitutes depends on several factors, including the type of wound and its severity. Full-thickness skin grafts (SGs) require a well-vascularised bed and sometimes will lead to contraction and scarring formation. Besides, donor sites for full-thickness skin grafts are very limited if the wound area is big, and it has been proven to have the lowest survival rate compared to thick- and thin-split thickness. Tissue engineering technology has introduced new advanced strategies since the last decades to fabricate the composite scaffold via the 3D-bioprinting approach as a tissue replacement strategy. Considering the current global donor shortage for autologous split-thickness skin graft (ASSG), skin 3D-bioprinting has emerged as a potential alternative to replace the ASSG treatment. The three-dimensional (3D)-bioprinting technique yields scaffold fabrication with the combination of biomaterials and cells to form bioinks. Thus, the essential key factor for success in 3D-bioprinting is selecting and developing suitable bioinks to maintain the mechanisms of cellular activity. This crucial stage is vital to mimic the native extracellular matrix (ECM) for the sustainability of cell viability before tissue regeneration. This comprehensive review outlined the application of the 3D-bioprinting technique to develop skin tissue regeneration. The cell viability of human skin cells, dermal fibroblasts (DFs), and keratinocytes (KCs) during in vitro testing has been further discussed prior to in vivo application. It is essential to ensure the printed tissue/organ constantly allows cellular activities, including cell proliferation rate and migration capacity. Therefore, 3D-bioprinting plays a vital role in developing a complex skin tissue structure for tissue replacement approach in future precision medicine.
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