Skin and skin appendages are vulnerable to injury, requiring rapidly reliable regeneration methods. In recent years, 3D bioprinting has shown potential for wound repair and regeneration. 3D bioprinting can be customized for skin shape with cells and other materials distributed precisely, achieving rapid and reliable production of bionic skin substitutes, therefore, meeting clinical and industrial requirements. Additionally, it has excellent performance with high resolution, flexibility, reproducibility, and high throughput, showing great potential for the fabrication of tissue-engineered skin. This review introduces the common techniques of 3D bioprinting and their application in skin tissue engineering, focusing on the latest research progress in skin appendages (hair follicles and sweat glands) and vascularization, and summarizes current challenges and future development of 3D skin printing.

Tissue-engineered skin (TES), as an analogue of native skin, is promising for wound repair and regeneration. However, a major drawback of TES products is a lack of skin appendages and nerves to enhance skin healing, structural integrity and skin vitality. Skin appendages and nerves are important constituents for fully functional skin. To date, many studies have yielded remarkable results in the field of skin appendages reconstruction and nerve regeneration. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients’ quality of life. Current strategies to create skin appendages and sensory nerve regeneration are mainly based on different types of seeding cells, scaffold materials, bioactive factors and involved signaling pathways. This article provides a comprehensive overview of different strategies for, and advances in, skin appendages and sensory nerve regeneration, which is an important issue in the field of tissue engineering and regenerative medicine.

Critical tissue defects frequently result from trauma, burns, chronic wounds and/or surgery. The ideal treatment for such tissue loss is autografting, but donor sites are often limited. Tissue engineering (TE) is an inspiring alternative for tissue repair and regeneration (TRR). One of the current state-of-the-art methods for TRR is gene therapy. Non-viral gene delivery systems (nVGDS) have great potential for TE and have several advantages over viral delivery including lower immunogenicity and toxicity, better cell specificity, better modifiability, and higher productivity. However, there is no ideal nVGDS for TRR, hence, there is widespread research to improve their properties. This review introduces the basic principles and key aspects of commonly-used nVGDSs. We focus on recent advances in their applications, current challenges, and future directions.

Early acute kidney injury (AKI) is a devastating complication in critical burn patients, and it is associated with severe morbidity and mortality. The mechanism of AKI is multifactorial. Astaxanthin (ATX) is a natural compound that is widely distributed in marine organisms; it is a strong antioxidant and exhibits other biological effects that have been well studied in various traumatic injuries and diseases. Hence, we attempted to explore the potential protection of ATX against early post burn AKI and its possible mechanisms of action. The classic severe burn rat model was utilized for the histological and biochemical assessments of the therapeutic value and mechanisms of action of ATX. Upon ATX treatment, renal tubular injury and the levels of serum creatinine and neutrophil gelatinase-associated lipocalin were improved. Furthermore, relief of oxidative stress and tubular apoptosis in rat kidneys post burn was also observed. Additionally, ATX administration increased Akt and Bad phosphorylation and further down-regulated the expression of other downstream pro-apoptotic proteins (cytochrome c and caspase-3/9); these effects were reversed by the PI3K inhibitor LY294002. Moreover, the protective effect of ATX presents a dose-dependent enhancement. The data above suggested that ATX protects against early AKI following severe burns in rats, which was attributed to its ability to ameliorate oxidative stress and inhibit apoptosis by modulating the mitochondrial-apoptotic pathway, regarded as the Akt/Bad/Caspases signalling cascade.

Gelatin methacryloyl (GelMA) hydrogels loaded with stem cells have proved to be an effective clinical treatment for wound healing. Advanced glycation end product (AGE), interacting with its particular receptor (AGER), gives rise to reactive oxygen species (ROS) and apoptosis. Curcumin (Cur) has excellent antioxidant activity and regulates intracellular ROS production and apoptosis. In this study, we developed a Cur-incorporated 3D-printed GelMA to insert into adipose-derived stem cells (ADSCs) and applied it to diabetic wounds. GelMA hydrogels with Cur were fabricated and their in vitro effects on ADSCs were investigated. We used structural characterization, western blot, ROS and apoptosis assay to evaluate the antioxidant and anti-apoptotic activity, and assessed the wound healing effects to investigate the mechanism underlying regulation of apoptosis by Cur via the AGE/AGER/nuclear factor-κB (NF-κB) p65 pathway. A 10% GelMA scaffold exhibited appropriate mechanical properties and biocompatibility for ADSCs. The circular mesh structure demonstrated printability of 10% GelMA and Cur-GelMA bioinks. The incorporation of Cur into the 10% GelMA hydrogel showed an inhibitory effect on AGEs/AGER/NF-κB p65-induced ROS generation and ADSC apoptosis. Furthermore, Cur-GelMA scaffold promoted cell survival and expedited in vivo diabetic wound healing. The incorporation of Cur improved the antioxidant activity of 3D-printed GelMA hydrogel and mitigated AGE/AGER/p65 axis-induced ROS and apoptosis in ADSCs. The effects of scaffolds on wound healing suggested that Cur/GelMA-ADSC hydrogel could be an effective biological material for accelerating wound healing.