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.

Full-thickness skin wounds have become a serious burden to patients, medical care, and the socio-economic environment. The development of a safe and effective acellular skin substitute that can rapidly restore intact physiological skin is required. Natural bioactive materials including collagen, gelatin, and elastin possess significant advantages over synthetic biomaterials regarding biodegradability and biocompatibility. However, low mechanical strength, a faster biodegradation rate, and thermally unstable biomaterials lead to slow-healing and a high rate of post-implantation failure. To overcome these concerns, naturally occurring genipin (GNP) flavonoids were added to improve the mechanical strength, degradation rate, and thermal properties. Therefore, this study aimed to fabricate and characterize collagen–gelatin–elastin (CollaGee) biomaterials cross-linked with GNP as an acellular skin substitute potentially used in full-thickness wound healing. CollaGee at different ratios was divided into non-cross-linked and cross-linked with 0.1% GNP (w/v). The physicochemical, mechanical, and biocompatibility properties of CollaGee were further investigated. The results demonstrated that GNP-cross-linked CollaGee has better physicochemical (>50% porosity, pore size range of 100–200 µm, swelling ratio of >1000%) and mechanical properties (resilience and cross-linking degree of >60%, modulus of >1.0 GPa) compared to non-cross-linked CollaGee groups. Furthermore, both cross-linked and non-cross-linked CollaGee demonstrated pivotal cellular compatibility with no toxicity and sustained cell viability until day 7 towards human dermal fibroblasts. These findings suggest that GNP-cross-linked CollaGee could be a promising ready-to-use product for the rapid treatment of full-thickness skin loss.

We report our experience of treating two patients with ankle amputation with different presentations. The first case was a clean-cut sharp amputation. The second case was an avulsion injury following a motor vehicle accident in a patient who arrived 8 hours after the injury. Replantation was successful in both cases. In avulsion injuries, a secondary operation for wound coverage is required at a later stage. With good strategy and a support team, encouraging limb survival outcomes are possible post-replantation.

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