PVA/PVP Nanofibres Incorporated with Ecklonia cava Phlorotannins Exhibit Excellent Cytocompatibility and Accelerate Hyperglycaemic Wound Healing.

BACKGROUND: Diabetic foot ulcer (DFU) is a major debilitating complication of diabetes. The lack of effective diabetic wound dressings has been a significant problem in DFU management. In this study, we aim to establish a phlorotannin-incorporated nanofibre system and determine its potential in accelerating hyperglycaemic wound healing. METHODS: The effective dose of Ecklonia cava phlorotannins (ECP) for hyperglycaemic wound healing was determined prior to phlorotannin nanofibre fabrication using polyvinyl-alcohol (PVA), polyvinylpyrrolidone (PVP), and ECP. Vapour glutaraldehyde was used for crosslinking of the PVA/PVP nanofibres. The phlorotannin nanofibres were characterised, and their safety and cytocompatibility were validated. Next, the wound healing effect of phlorotannin nanofibres was determined with 2D wound scratch assay, whereas immunofluorescence staining of Collagen-I (Col-I) and Cytokeratin-14 (CK-14) was performed in human dermal fibroblasts (HDF) and human epidermal keratinocytes (HEK), respectively. RESULTS: Our results demonstrated that 0.01 µg/mL ECP significantly improved hyperglycaemic wound healing without compromising cell viability and proliferation. Among all nanofibres, PVA/PVP/0.01 wt% ECP nanofibres exhibited the best hyperglycaemic wound healing effect. They displayed a diameter of 334.7 ± 10.1 nm, a porosity of 40.7 ± 3.3%, and a WVTR of 1718.1 ± 32.3 g/m2/day. Besides, the FTIR spectra and phlorotannin release profile validated the successful vapour glutaraldehyde crosslinking and ECP incorporation. We also demonstrated the potential of phlorotannin nanofibres as a non-cytotoxic wound dressing as they support the viability and proliferation of both HDF and HEK. Furthermore, phlorotannin nanofibres significantly ameliorated the impaired hyperglycaemic wound healing and restored the hyperglycaemic-induced Col-I reduction in HDF. CONCLUSION: Taken together, our findings show that phlorotannin nanofibres have the potential to be used as a diabetic wound dressing.

Molecular pathways of NF-ĸB and NLRP3 inflammasome as potential targets in the treatment of inflammation in diabetic wounds: A review.

Diabetic wounds are slow healing wounds characterized by disordered healing processes and frequently take longer than three months to heal. One of the defining characteristics of impaired diabetic wound healing is an abnormal and unresolved inflammatory response, which is primarily brought on by abnormal macrophage innate immune signaling activation. The persistent inflammatory state in a diabetic wound may be attributed to inflammatory pathways such as nuclear factor kappa B (NF-ĸB) and nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which have long been associated with inflammatory diseases. Despite the available treatments for diabetic foot ulcers (DFUs) that include debridement, growth factor therapy, and topical anti-bacterial agents, successful wound healing is still hampered. Further understanding of the molecular mechanism of these pathways could be useful in designing potential therapeutic targets for diabetic wound healing. This review provides an update and novel insights into the roles of NF-ĸB and NLRP3 pathways in the molecular mechanism of diabetic wound inflammation and their potential as therapeutic targets in diabetic wound healing.

Advancements in Extracellular Matrix-Based Biomaterials and Biofabrication of 3D Organotypic Skin Models.

Over the last decades, three-dimensional (3D) organotypic skin models have received enormous attention as alternative models to in vivo animal models and in vitro two-dimensional assays. To date, most organotypic skin models have an epidermal layer of keratinocytes and a dermal layer of fibroblasts embedded in an extracellular matrix (ECM)-based biomaterial. The ECM provides mechanical support and biochemical signals to the cells. Without advancements in ECM-based biomaterials and biofabrication technologies, it would have been impossible to create organotypic skin models that mimic native human skin. In this review, the use of ECM-based biomaterials in the reconstruction of skin models, as well as the study of complete ECM-based biomaterials, such as fibroblasts-derived ECM and decellularized ECM as a better biomaterial, will be highlighted. We also discuss the benefits and drawbacks of several biofabrication processes used in the fabrication of ECM-based biomaterials, such as conventional static culture, electrospinning, 3D bioprinting, and skin-on-a-chip. Advancements and future possibilities in modifying ECM-based biomaterials to recreate disease-like skin models will also be highlighted, given the importance of organotypic skin models in disease modeling. Overall, this review provides an overview of the present variety of ECM-based biomaterials and biofabrication technologies available. An enhanced organotypic skin model is expected to be produced in the near future by combining knowledge from previous experiences and current research.