In recent years, bioprinting has attracted much attention as a potential tool for generating complex 3D biological constructs capable of mimicking the native tissue microenvironment and promoting physiologically relevant cell–cell and cell–matrix interactions. The aim of the present study was to develop a crosslinked 3D printable hydrogel based on biocompatible natural polymers, gelatin and xanthan gum at different percentages to be used both as a scaffold for cell growth and as a wound dressing. The CellInk Inkredible 3D printer was used for the 3D printing of hydrogels, and a glutaraldehyde solution was tested for the crosslinking process. We were able to obtain two kinds of printable hydrogels with different porosity, swelling and degradation time. Subsequently, the printed hydrogels were characterized from the point of view of biocompatibility. Our results showed that gelatin/xanthan-gum bioprinted hydrogels were biocompatible materials, as they allowed both human keratinocyte and fibroblast in vitro growth for 14 days. These two bioprintable hydrogels could be also used as a helpful dressing material.

The neutrophils extracellular traps (NETs) are a meshwork of chromatin, histonic and non-histonic proteins, and microbicidal agents spread outside the cell by a series of nuclear and cytoplasmic events, collectively called NETosis. NETosis, initially only considered a defensive/apoptotic mechanism, is now considered an extreme defensive solution, which in particular situations induces strong negative effects on tissue physiology, causing or exacerbating pathologies as recently shown in NETs-mediated organ damage in COVID-19 patients. The positive effects of NETs on wound healing have been linked to their antimicrobial activity, while the negative effects appear to be more common in a plethora of pathological conditions (such as diabetes) and linked to a NETosis upregulation. Recent evidence suggests there are other positive physiological NETs effects on wound healing that are worthy of a broader research effort.

Neutrophils are the most abundant type of immune cells and also the most underestimated cell defenders in the human body. In fact, their lifespan has also been extensively revised in recent years, going from a half-life of 8–10 h to a longer lifespan of up to 5.4 days in humans; it has been discovered that their mechanisms of defense are multiple and finely modulated, and it has been suggested that the heterogeneity of neutrophils occurs as well as in other immune cells. Neutrophils also play a critical role in the wound healing process, and their involvement is not limited to the initial stages of defense against pathogens, but extends to the inflammatory phase of tissue reconstruction. Neutrophil heterogeneity has recently been reported at the presence of distinct subtypes expressing different functional states, which contribute uniquely to the different phases of innate immunity and wound healing. This heterogeneity can be induced by the local microenvironment, by the presence of specific cytokines and by the type of injury. The different functional states of neutrophils enable a finely tuned response to injury and stress, which is essential for effective healing. Understanding the functional heterogeneity of neutrophils in wound healing can unveil potential pathological profiles and therapeutic targets. Moreover, the understanding of neutrophil heterogeneity dynamics could help in designing strategies to manage excessive inflammation or impaired healing processes. This review highlights the complexity of neutrophil heterogeneity and its critical roles throughout the phases of wound healing.

The lymphatic system is of fundamental importance in maintaining a fluid balance in the body and tissue homeostasis; it drains protein-rich lymph from the interstitial space and facilitates the release of cells that mediate the immune response. When one tissue is damaged, more cells and tissues work to repair the damaged site. Blood and lymph vessels are particularly important for tissue regeneration and healing. Angiogenesis is the process of the formation of new blood vessels and is induced by angiogenic factors such as VEGF-A; VEGF-C/D-induced lymphangiogenesis and both occur simultaneously during wound healing. After the inflammatory phase, lymphatic vessels suppress inflammation by aiding in the drainage of inflammatory mediators; thus, disorders of the lymphatic system often result in chronic and disabling conditions. It has recently been clarified that delayed wound healing, as in diabetes, can occur as a consequence of impaired lymphangiogenesis. In this review, we have highlighted recent advances in understanding the biology underlying lymphangiogenesis and its key role in wound healing, and the possibility of its pharmacological modulation as a novel therapeutic strategy for the treatment of chronic wounds.

We investigated the dimensional and mechanical properties of polyetetrafluorene (ePTFE) sutures used as artificial chordae during mitral valve repair. Mechanical properties of ePTFE synthetic chordae tendineae were tested with a servo hydraulic testing machine. Several different lengths from 2 to 14 cm were studied under both single and multiple mechanical traction. The mechanical behavior of artificial chordae reveals that three centimeters is the length over which we observe a significant increase in stiffness. The chordae stiffness grows further at the length greater than seven centimeters following a low number of traction cycles. The increase of the length of artificial ePTFE chordae is accompanied by an increasing stiffness that compromises the long-term resistance of the chordae. ePTFE length can alter the performance of artificial chordae. This suggests that mitral valve repairs which anchor ePTFE neochordae to the ventricular apex may have less durability than when anchored to the tips of the papillary muscles.