Inertia-driven, self-powered electrotherapy for enhanced wound regeneration

Diabetic wounds are often chronic in nature, and issues like elevated blood sugar, bacterial infections, oxidative stress and persistent inflammation impede the healing process. To ensure the appropriate healing of wounds, scaffolds should promote complete tissue regeneration in wounds, both functionally and structurally. However, the available scaffolds lack the explicit architecture and functionality that could match those of native skin, thus failing to carry out the scar-free skin regeneration in diabetic wounds. This study deals with the synthesis of a bi-layered nanofibrous scaffold mimicking the native skin architecture in terms of porosity and hydrophobic-hydrophilic gradients. In addition, herbal extracts of Aloe vera and litchi honey were added in consecutive layers to manage the high blood glucose level, inflammation, and increased ROS level associated with diabetic wounds. In vitro studies confirmed that the prepared scaffold with herbal extracts showed enhanced proliferation of skin cells with good mechanical strength, degradability, anti-bacterial and anti-diabetic properties. The scaffold also demonstrated superior wound healing in vivo with quicker scar-free wound recovery and appropriate skin regeneration, compared to conventional treatment. Altogether, the synthesized herbal extract loaded bi-layered nanofibrous scaffold can be used as a regenerative template for hard-to-heal diabetic wounds, offering a new strategy for the management of chronic wounds.

The management of complex acute and chronic wounds remains a formidable challenge in modern medicine, underscoring the urgent need for advanced therapeutic strategies that accelerate healing, prevent infection, and promote functional tissue regeneration. Electrospun nanofibers have attracted considerable attention in the biomedical field due to their extracellular matrix-like architecture, high surface area, interconnected porosity, and tunable physicochemical composition, which drive advances in wound regeneration, tissue engineering, and biopolymer-based therapeutics. In wound healing, nanofibrous dressings composed of natural polymers such as chitosan, gelatin, collagen, and cellulose promote cell attachment and proliferation, support angiogenesis, and enable infection control while delivering bioactive agents, thereby addressing significant challenges related to inflammation, biocompatibility, and antimicrobial resistance. In tissue engineering, aligned and hierarchically organized scaffolds fabricated from biopolymers such as collagen, gelatin, chitosan, and cellulose enhance the guided orientation of cells, differentiation, and functional regeneration of neural, musculoskeletal, vascular, and skin tissues. In addition to their conventional regenerative applications, recent studies have demonstrated that electrospun biopolymer nanofibers can be used in multifunctional biomedical platforms, including smart and stimuli-responsive systems for drug delivery, biosensing, regenerative interfaces, and wearable medical technologies. The integrated constructs that incorporate diagnostic or therapeutic functionalities, hybrid fabrication approaches that combine 3D printing with electrospinning, and intelligent biopolymer frameworks that enable telemedicine, real-time physiological monitoring, and personalized regenerative therapies offer new opportunities for developing improved biomedical systems. Overall, these advances position electrospun nanofiber systems as promising biomaterials for next-generation biomedical innovation. This review summarizes recent progress in tissue-engineered scaffolds, wound dressings, fabrication strategies for integrative therapeutics, and wearable devices with transformative potential for biomedical applications. Finally, the review addresses significant challenges related to scalability and clinical translation. It offers perspectives on future directions, including the integration of artificial intelligence and the regeneration of complex skin appendages, which will shape the next generation of nanofiber-based wound-healing therapies.

Many lizards are able to undergo scar-free wound healing and regeneration following loss of the tail. In most instances, lizard tail loss is facilitated by autotomy, an evolved mechanism that permits the tail to be self-detached at pre-existing fracture planes. However, it has also been reported that the tail can regenerate following surgical amputation outside the fracture plane. In this study, we used the leopard gecko, Eublepharis macularius, to investigate and compare wound healing and regeneration following autotomy at a fracture plane and amputation outside the fracture plane. Both forms of tail loss undergo a nearly identical sequence of events leading to scar-free wound healing and regeneration. Early wound healing is characterized by transient myofibroblasts and the formation of a highly proliferative wound epithelium immunoreactive for the wound keratin marker WE6. The new tail forms from what is commonly referred to as a blastema, a mass of proliferating mesenchymal-like cells. Blastema cells express the protease matrix metalloproteinase-9. Apoptosis (demonstrated by activated caspase 3 immunostaining) is largely restricted to isolated cells of the original and regenerating tail tissues, although cell death also occurs within dermal structures at the original-regenerated tissue interface and among clusters of newly formed myocytes. Furthermore, the autotomized tail is unique in demonstrating apoptosis among cells adjacent to the fracture planes. Unlike mammals, transforming growth factor-β3 is not involved in wound healing. We demonstrate that scar-free wound healing and regeneration are intrinsic properties of the tail, unrelated to the location or mode of tail detachment.

Significance: Skin scarring poses a major biomedical burden for hundreds of millions of patients annually. However, this burden could be mitigated by therapies that promote wound regeneration, with full recovery of skin's normal adnexa, matrix ultrastructure, and mechanical strength. Recent Advances: The observation of wound regeneration in several mouse models suggests a retained capacity for postnatal mammalian skin to regenerate under the right conditions. Mechanical forces are a major contributor to skin fibrosis and a prime target for devices and therapeutics that could promote skin regeneration. Critical Issues: Wound-induced hair neogenesis, Acomys "spiny" mice, Murphy Roths Large mice, and mice treated with mechanotransduction inhibitors all show various degrees of wound regeneration. Comparison of regenerating wounds in these models against scarring wounds reveals differences in extracellular matrix interactions and in mechanosensitive activation of key signaling pathways, including Wnt, Sonic hedgehog, focal adhesion kinase, and Yes-associated protein. The advent of single-cell "omics" technologies has deepened this understanding and revealed that regeneration may recapitulate development in certain contexts, although it is unknown whether these mechanisms are relevant to healing in tight-skinned animals such as humans. Future Directions: While early findings in mice are promising, comparison across model systems is needed to resolve conflicting mechanisms and to identify conserved master regulators of skin regeneration. There also remains a dire need for studies on mechanomodulation of wounds in large, tight-skinned animals, such as red Duroc pigs, which better approximate human wound healing.

The biomedical domain has witnessed a significant incorporation of nanotechnology in recent years. Zeolitic imidazolate framework-8 (ZIF-8) has demonstrated potential as a pH-responsive smart targeted release nanoplatform for antibacterial and anti-inflammatory agents, attributed to its superior biocompatibility and robust physicochemical stability. Furthermore, the high porosity and substantial surface area of ZIF-8 enable significant drug-loading capacity and the encapsulation of various agents, including small inorganic molecules and large protein molecules. Moreover, ZIF-8 composite materials exhibit unique pH sensitivity and photosensitivity, resulting in decomposition and subsequent release of antibacterial and anti-inflammatory agents under acidic conditions and near-infrared irradiation, respectively. This review aims to synthesize recent advancements in pH-responsive and photosensitive ZIF-8 as a dual-responsive smart targeted release nanoplatform in antibacterial therapy and wound regeneration. Furthermore, this review elucidates the benefits and operational principles of ZIF-8 as a smart targeted release nanoplatform for antibacterial efficacy and wound healing, with the objective of providing a comprehensive rationale and guidance for investigations into the antibacterial properties and the promotion of wound regeneration facilitated by ZIF-8.

Wound healing activity of the human antimicrobial peptide LL37

Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing.

Construction of a biomimetic chemokine reservoir stimulates rapid in situ wound repair and regeneration.

Hemibody irradiation in multiple fractionated doses is frequently used for the treatment of various neoplastic disorders. It produces both acute and late effects on the skin and subcutaneous tissues that have profound implications in the healing of surgical wounds. Because of the crucial practical importance of hemibody radiation exposure associated with skin wounds, it is imperative to investigate the efficacy of cost-effective herbal products in the reconstruction of irradiated wounds. Therefore, the effect of pretreatment of curcumin was studied on the healing of excision wound in mice exposed to 2, 4, 6, or 8 Gy of hemibody gamma-radiation. A full-thickness skin wound was created by removing the skin flap of the dorsum of 8- to 10-week-old Swiss albino mice partially (lower half, below the rib cage) exposed to 2, 4, 6, or 8 Gy of gamma-radiation. The progression of wound contraction was monitored periodically by capturing video images of the wound, where the first image of each wound from different groups was obtained 1 day after wounding and that day was considered as day 0. Eight animals were used in each group at each exposure dose for wound contraction studies. Furthermore, the effect of curcumin on mean healing time after exposure of mice to 2, 4, 6, or 8Gy of hemibody gamma-radiation was also evaluated, where eight animals were used in each group at each exposure dose. Collagen, hexosamine, DNA, nitric oxide, and histologic profiles were also evaluated during the course of healing of excision wounds at days 4, 8, and 12 after irradiation treated or not with curcumin before exposure to 0 or 6 Gy of gamma-radiation. Six animals were used in each group at each interval for each biochemical parameter studied, except for histologic evaluations, where four animals were used in each group at each interval. Exposure of mice to different doses of gamma-radiation resulted in a dose-dependent delay in contraction and wound-healing time of excision wound, whereas curcumin pretreatment caused a significant elevation in the rate of wound contraction and a decrease in the mean wound-healing time. Treatment with curcumin before irradiation enhanced the synthesis of collagen, hexosamine, DNA, nitrite, and nitrate, and histologic assessment of wound biopsy specimens revealed improved collagen deposition and an increase in fibroblast and vascular densities. The authors' study demonstrates that curcumin pretreatment has a conducive effect on the irradiated wound and could be a substantial therapeutic strategy for ameliorating radiation-induced delay in wound repair in cases of radiation-induced skin injuries.

In this paper the results of an experimental-clinical study substantiating the use of low level laser radiation (LLLR) at certain wavelengths for treatment of cancer patients are given. In the first part of this study, with animal experiments, laser action parameters providing reliable renewal and regeneration stimulation are selected. It is shown that, under the effect of LLLR, the speed and quality of regeneration in wounds after tumor removal are changed as well as the intensity of dissemination and tumor growth. A change also occurs in the functional properties of lymphocytes, which have immunological control in the organism. On the basis of the experimental data obtained, the contingent of cancer patients for whom LLLR can be recommended was determined.

Hyperbaric oxygen therapy (HBOT) is thought to promote vascular regeneration in wounds. The purpose of this study was to investigate the role of HBOT in advancing vascular regeneration in healing oral mucosal surgical flaps. A palatine partial-thickness mucosal flap was raised in 10 male-specific pathogen-free New Zealand White rabbits. Randomized into 2 groups of 5 animals each (control and HBOT), functional capillary density was measured preoperatively (baseline), and immediately postoperatively until day 21 using sidestream dark-field video microscopy. Ten HBOT sessions were administered over the course of 2 weeks at 2.5 atmospheres (2.5 bar O2 /90 minutes). Repeated measures analysis of variance was used to compare the HBOT and control group on the sequential functional capillary density measurements. A significant interaction effect was present between time and group (F [8, 64] = 9.60; p < .0001) resulting from a significant increase in microcirculation in the HBOT group relative to the control group on days 7, 9, and 11. Our results suggest that HBOT is capable of advancing wound vascular regeneration in healing keratinized oral mucosal flaps.

The intact and healthy skin forms a barrier to the outside world and protects the body from mechanical impact. The skin is a complex structure with unique mechano-elastic properties. To better direct the design of biomimetic materials and induce skin regeneration in wounds with optimal outcome, more insight is required in how the mechano-elastic properties emerge from the skin’s main constituents, collagen and elastin fibers. Here, we employed two-photon excited autofluorescence and second harmonic generation microscopy to characterize collagen and elastin fibers in 3D in 24 human dermis skin samples. Through uniaxial stretching experiments, we derive uni-directional mechanical properties from resultant stress-strain curves, including the initial Young’s modulus, elastic Young’s modulus, maximal stress, and maximal and mid-strain values. The stress-strain curves show a large variation, with an average Young’s modules in the toe and linear regions of 0.1 MPa and 21 MPa. We performed a comprehensive analysis of the correlation between the key mechanical properties with age and with microstructural parameters, e.g., fiber density, thickness, and orientation. Age was found to correlate negatively with Young’s modulus and collagen density. Moreover, real-time monitoring during uniaxial stretching allowed us to observe changes in collagen and elastin alignment. Elastin fibers aligned significantly in both the heel and linear regions, and the collagen bundles engaged and oriented mainly in the linear region. This research advances our understanding of skin biomechanics and yields input for future first principles full modeling of skin tissue.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10237-023-01813-3.

Fish rely, to a high degree, on the innate immune system to protect them against the constant exposure to potential pathogenic invasion from the surrounding water during homeostasis and injury. Zebrafish larvae have emerged as an outstanding model organism for immunity. The cellular component of zebrafish innate immunity is similar to the mammalian innate immune system and has a high degree of sophistication due to the needs of living in an aquatic environment from early embryonic stages of life. Innate immune cells (leukocytes), including neutrophils and macrophages, have major roles in protecting zebrafish against pathogens, as well as being essential for proper wound healing and regeneration. Zebrafish larvae are visually transparent, with unprecedented in vivo microscopy opportunities that, in combination with transgenic immune reporter lines, have permitted visualisation of the functions of these cells when zebrafish are exposed to bacterial, viral and parasitic infections, as well as during injury and healing. Recent findings indicate that leukocytes are even more complex than previously anticipated and are essential for inflammation, infection control, and subsequent wound healing and regeneration.

Wound Repair and Regenerationis the official, peer-reviewed of the European Tissue Repair Society (ETRS) and the Wound Healing Society (WHS). These societies were incorporated in 1988 and 1989, respectively. As a publication of the latest information on wound healing, repair, and regeneration, this journal fulfills an objective of both the ETRS and the WHS. A thorough review of the first five issues ofWound Repair and Regenerationconfirms the perception that the editors' intent to facilitate production of a greater progress towards the understanding of the process of wound healing is well achieved. The field of wound healing, previously dominated by surgeons, dermatologists, and pathologists, has widened to include the investigations of other specialists. Consequently, state-of-the-art molecular biology, immunology, and bioengineering join the traditional basic sciences to occupy a prominent place inWound Repair and Regeneration, as manifested by a preponderance of original articles dedicated to the purely

Branching scleractinian corals are niche-constructing organisms, providing continuously-growing, structural foundation for spectacularly biodiverse coral reef ecosystems. A large part of their success lies in the ability to quickly regenerate following mechanical damage. Even now, when the corals undergo great decline due to anthropogenic weather and storm extremes, it is surprising how little is known about molecular mechanisms governing regeneration in these iconic organisms. In this study, we used RNA-seq to identify genes involved in the regeneration of Acropora millepora, starting with the initial wound closure up to complete rebuilding of lost structures. Many of the differentially expressed genes we found in the wound healing steps are homologues of genes known to be involved in wound healing and regeneration of bilaterian and other cnidarian species, prominently including multiple components of FGF and Wnt signalling pathways. Comparison between genes involved in wound healing and continuous growth of the colony demonstrates both similarity and distinctiveness of the genetic programmes controlling these processes. A striking example is specific expression of c-Fos, a transcription factor with conserved role in early injury response, during the earliest stages of wound healing of A. millepora. By comparing results obtained in diverse experimental conditions including a closed-loop, recirculating aquarium and a flow-through system of marine station, we have demonstrated feasibility of using zooxanthellate scleractinian corals as experimental models in fundamental biology research, including studies of regeneration.