Chitosan-gallic acid conjugates were synthesized by carbodiimide method and characterized by physicochemical methods (UV-vis, FTIR, 1H NMR, TGA). The FTIR and NMR assays confirmed that the chemical interaction occurred solely due to the formation of an amide bond. It was established that by varying the ratio of the components during synthesis it is possible to obtain conjugates with desired conjugation ratio, grafting efficiency and gallic acid content up to 8.09 ± 1.72 %, 70.51 ± 9.45 % and 79.9 ± 2.4 μg gallic acid/mg chitosan, respectively. Chitosan-gallic acid conjugate with a 5 % conjugation ratio demonstrated excellent antioxidant properties: the IC50 value for ABTS radical scavenging activity was 0.0073 ± 0.0001 mg/mL. In vitro tests showed that conjugation of chitosan with gallic acid provided the antiglycemic activity of the material and its good biocompatibility. A low level of cytotoxicity was recorded in the HaCaT cell line model (IC50 was 1030.4 μg/mL). The received eco-friendly chitosan-gallic acid conjugate effectively inhibited the growth of thermophilic spore-forming bacteria G. thermodenitrificans and the resistant to classical antibiotics strain A. palidus. The results of an in vivo comparative analysis showed that chitosan-gallic acid conjugate had excellent wound healing properties due to the synergism of the polysaccharide and the natural antioxidant.

Diabetes mellitus is a chronic disease that has become more prevalent worldwide because of lifestyle changes. It leads to serious complications, including increased atherosclerosis, protein glycosylation, endothelial dysfunction, and vascular denervation. These complications impair neovascularization and wound healing, resulting in delayed recovery from injuries and an elevated risk of infections. The present study aimed to investigate the effect of lipoic acid (LA) on the key mediators involved in the wound healing process, specifically CD4 + CD25 + T cell subsets, CD4 + CD25 + Foxp3 + regulatory T (Treg) cells, T-helper-17 (Th17) cells that generate IL-17 A, glucocorticoid-induced tumor necrosis factor receptor (GITR) expressing cells, as well as cytokines such as IL-2, IL-1β, IL-6, and TNF-α and IFN-γ. These mediators play crucial roles in epidermal and dermal proliferation, hypertrophy, and cell migration.

We divided mice into 5 groups: the non-diabetic (normal control; NC), wounded non-diabetic mice (N + W), wounded diabetic mice (D + W), wounded diabetic mice treated with 50 mg/kg lipoic acid (D + W + L50) for 14 days, and wounded diabetic mice treated with 100 mg/kg lipoic acid (D + W + L100) for 14 days.

Flow cytometric analysis indicated that lipoic acid-treated mice exhibited a significant decrease in the frequency of intracellular cytokines (IL-17 A, TNF-α and IFN-γ) in CD4 + T cells, as well as a reduction in the number of GITR-expressing cells. Conversely, a significant upregulation in the number CD4+, CD25+, FOXp3 + and CD4 + CD25 + Foxp3 + regulatory T (Treg) cells was observed in this group compared to both the normal + wounded (N + W) and diabetic + wounded (D + W) groups. Additionally, the mRNA Levels of inflammatory mediators (IL-2, IL-1β, IL-6, and TNF-α) were downregulated in lipoic acid-treated mice compared to other groups. T thereby he histological findings of diabetic skin wounds treated with lipoic acid showed well-healed surgical wounds.

These findings support the beneficial role of lipoic acid in fine-tuning the balance between anti-inflammatory and pro-inflammatory cytokines, influencing both their release and gene expression.

Infected wounds are common clinical injuries that often complicated by inflammation and oxidative stress due to bacterial invasion. These wounds typically suffer from impaired vascularization, which delays healing and increases the risk of complications such as sepsis and chronic wounds. Therefore, developing an effective treatment for infected wounds is highly necessary. Egg white can promote cell regeneration and repair, while chitosan is effective in resisting bacterial invasion. Sildenafil is believed to have the potential to promote angiogenesis. Based on these properties, we have prepared a new type of hydrogel using egg white and chitosan as the framework, loaded with sildenafil (CEHS). The hydrogel combines the benefits of its components, exhibiting good biocompatibility and promoting the proliferation and migration of NIH 3T3 (3T3) cells and human umbilical vein endothelial cells (HUVEC), as well as the angiogenesis in HUVEC. It also exhibits significant antioxidant, anti-inflammatory, and antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Additionally, in a mouse model of infected wounds, the CEHS effectively promoted wound healing through its excellent antioxidant and anti-inflammatory properties, antibacterial activity, and pro-angiogenic effects. In summary, this simple-to-prepare, multifunctional natural hydrogel shows great promise for the treatment of infected wounds.

A diabetic wound (DW) is an alteration in the highly orchestrated physiological sequence of wound healing especially, the inflammatory phase. These alterations result in the generation of oxidative stress and inflammation at the injury site. This further leads to the impairment in the angiogenesis, extracellular matrix, collagen deposition, and re-epithelialization. Additionally, in DW there is the presence of microbial load which makes the wound worse and impedes the wound healing cycle. There are several treatment strategies which have been employed by the researchers to mitigate the aforementioned challenges. However, they failed to address the multifactorial pathogenic nature of the disease. Looking at the severity of the disease researchers have explored snail mucus and its components such as achacin, allantoin, elastin, collagen, and glycosaminoglycan due to its multiple therapeutic potentials; however, glycosaminoglycan (GAGs) is very important among all because they accelerate the wound-healing process by promoting reepithelialization, vascularization, granulation, and angiogenesis at the site of injury. Despite its varied applications, the field of snail mucus in wound healing is still underexplored. The present review aims to highlight the role of snail mucus in diabetic wound healing, the advantages of snail mucus over conventional treatments, the therapeutic potential of snail mucus, and the application of snail mucus in DW. Additionally, clinical trials, patents, structural variations, and advancements in snail mucus characterization have been covered in the article.

Silk fibroin (SF) is a natural polymeric material that has attracted intense research attention in the field of wound healing due to its exceptional mechanical properties, tunable biodegradability, and multifunctional bioactivity. This review systematically summarizes the preparation strategies, functional modifications, and multidimensional application mechanisms of SF and its composite materials in wound healing. The innovative applications of SF in intelligent dressing design, immunometabolic regulation, controlled drug release, stem-cell function modulation, and bioelectrical-activity-mediated microenvironment remodeling is further explored, while analyzing the therapeutic efficacy and cost-effectiveness of SF through clinical translation cases. Distinct from previous reviews, this work not only integrates the latest advances in SF molecular mechanisms and material design but also emphasizes its potential in precision medicine, such as the development of genetically engineered SF for customized immunoregulatory networks. Finally, the article highlights the current challenges in the development of SF materials, including mechanical stability, degradation controllability, and standardization of large-scale production, and envisions future research directions driven by 3D bioprinting and synthetic biology technologies. This review provides a theoretical foundation and technical reference information for the development of efficient, multifunctional, and clinically translatable SF-based materials for application in wound healing.

Wound infections are one of the major threats to human health, accounting for millions of deaths annually. Real-time monitoring, accurate diagnosis, and on-demand therapy are crucial to minimizing complications and saving lives. Herein, we propose a "monitor-and-treat" strategy for infected wound management by integrating the emerging development of bacterio-therapeutics and bio-optics. The upper layer consists of gelatin methacryloyl (GelMA)-collagen III methacryloyl (Col3MA) (GC), Reuterin (Reu) isolated from the probiotic Lactobacillus reuteri (L. reuteri) and microfluidic safflower polysaccharide (SPS)@GelMA microspheres using 3D printing technology. The lower layer is made of acryloylated glycine (ACG) hydrogel with tissue adhesion capability, which enables the hydrogel to adapt to the movement and stretching of the skin. By integrating temperature-sensitive polydimethylsiloxane (PDMS) optical fibers, the ACG-GC/Reu/SPS-PDMS hydrogel could accurately and steadily sense and send wound temperature information to intelligent devices for real-time monitoring of the healing status ("monitor"). The double-layered hydrogel not only inhibited bacterial survival and colonization (97.4 % against E. coli and 99 % against S. aureus), but also exhibited remarkable hemostatic properties. Furthermore, it was conducive to L929 cell proliferation and pro-angiogenesis, and promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype, therefore creating a favorable immune microenvironment at the wound site. Animal experiments using SD rats and Bama minipigs demonstrated that this hydrogel promoted wound closure, directed polarization to M2 macrophages, alleviated inflammation, enhanced neovascularization, therefore accelerating infected wound healing ("treat"). In addition, RNA-Seq analysis revealed the mechanism of action of ACG-GC/Reu/SPS-PDMS hydrogel in modulating key signaling pathways, including down-regulation of AMPK, IL-17, and NF-κB signaling pathways, activation of NLRP3 inflammatory vesicles, and enrichment of MAPK, TGF-β, PI3K-Akt, TNF, and VEGF signaling pathways. The modulation of these signaling pathways suggests that hydrogels play an important role in the molecular mechanisms that promote wound healing and tissue regeneration. Therefore, the design of this study provides an innovative and multifunctional bandage strategy that can significantly improve pathologic diagnosis and wound treatment.

Radionecrosis of skin (RNS) is the severe consequence of radiodermatitis (RD), which is a common complication experienced in up to 95 % of cancer patients after radiation therapy (RT). Recent publications revealed an absence of grading criteria for RNS and only crude forms for RD. However, treatments for RNS of different severity vary widely in terms of treatment difficulty and prognosis. This Delphi study aims to provide wound repair surgeons and oncologists a comprehensive guide for accurate RNS diagnosis, facilitating more effective surgical or operative interventions.

A three-round Delphi method was conducted between May and September 2022, involving 24 experts who specialize in the care or research of RNS. The process identified and weighted primary and secondary items to create a scale that reflects the severity of RNS. A receiver operating characteristic (ROC) curve was generated using the expert's ratings (n = 15) as the benchmark to establish the grading criteria on RNS (GCRNS) with patient data (n = 64). To assess test-retest reliability, 32 physicians re-evaluate 64 patients' files 2 weeks after their initial evaluation. The correlation between expert ratings and physician's re-evaluated grading was calculated to confirm concurrent validity.

The final GCRNS consisted of 18 secondary items categorized under 6 primary items, including ulcer duration, peripheral skin, ulcer area, underlying disease, ulcer depth, and severe complications. Severity classification thresholds were proposed by ROC curve, defining severity levels as mild, moderate, and severe. Six primary items were positively correlated the severity of RNS with affirming its concurrent validity (r = 0.751, p < 0.001). Good internal consistency (α=0.831) and test-retest reliability (r = 0.969, p < 0.001) were demonstrated.

GCRNS is an expert-driven and comprehensive approach to RNS assessment for further wound repair. By improving diagnostic accuracy, particularly among junior surgeons, GCRNS with strong concurrent validity and reliability, enhances clinical decision-making and supports more effective treatment planning.

Wound management is a critical aspect of healthcare, necessitating continuous monitoring and timely interventions to ensure optimal healing outcomes. In recent years, the integration of sensor technology into wound dressings has emerged as a transformative approach, enabling real-time monitoring of healing parameters and facilitating on-demand treatment delivery. Sensor-based wound dressings leverage various sensing modalities, including temperature, pH, moisture, oxygen, and other biochemical markers, to provide comprehensive insights into the wound microenvironment. These dressings are equipped with miniaturized sensors capable of transmitting the data wirelessly, facilitating remote monitoring and timely interventions. Moreover, some advanced dressings incorporate responsive drug delivery systems, enabling the on-demand release of therapeutics based on real-time sensor feedback. Additionally, the incorporation of on-demand treatment mechanisms allows targeted delivery of therapeutics based on the specific needs of the wound, further enhancing the efficacy of the healing process. This comprehensive approach improves patient outcomes by promoting faster and more effective wound healing and reducing the burden through streamlined monitoring and treatment protocols. This paper presents an overview of recent advancements in sensor technology applied to wound healing, focusing on their role in monitoring wound parameters and delivering targeted therapy. These sensors leverage temperature, pH, and glucose sensing modalities to provide comprehensive insights into the healing process.

High-intensity focused ultrasound (HIFU) has demonstrated efficacy as a non-invasive treatment for uterine fibroids, though individual variability exists. This study aims to develop a risk scoring model using clinical and biochemical features to predict HIFU treatment outcomes.

This study collected clinical data from patients receiving HIFU treatment, including demographic characteristics, clinical symptoms, treatment information, and biochemical indicators. A risk scoring model was constructed using the random forest analysis method, and its performance was evaluated. Meanwhile, the impact of risk models and other factors on the efficacy of HIFU was evaluated. Furthermore, the interrelationships between the risk model and other factors were explored through interaction analysis. Finally, a nomogram was developed to evaluate its clinical utility.

The risk model, 4 or more treatments, age, and tumor necrosis factor levels were identified as independent influencing factors, with the risk model demonstrating the best performance (area under the curve (AUC) = 0.693). Interaction analysis revealed a significant synergistic effect between the risk model and receiving 4 or more treatments. The nomogram analysis indicated that lower risk scores and fewer treatment sessions were associated with better HIFU treatment outcomes. The receiver operating characteristic curves and calibration curves in both the training and validation sets demonstrated good performance of the nomogram.

This study successfully constructed a risk scoring model based on clinical features and biochemical indicators, which can effectively predict the efficacy of HIFU treatment for uterine fibroids. There is a significant interaction between the risk model and 4 or more treatments. The constructed nomogram provides strong support for individualized treatment.

Cotton has long been regarded as a naturally abundant and clinically indispensable material for medical textiles. Cotton gauze, a cornerstone material in wound management due to its inherent fluid absorption capacity, faces limitations in simultaneously addressing hemorrhage and infection. In this work, we developed a multifunctional wound dressing by functionalizing commercial cotton gauze with a tannic acid-assisted layer-by-layer assembly strategy to immobilize zinc-based metal-organic frameworks (Zn-BDC). The resulting cg@PTA@Zn-BDC-5 dressing synergizes the intrinsic advantages of cotton textiles with advanced functionalities, achieving a 76.4 % reduction in blood clotting time through Zn2+-activated coagulation cascades and enhanced platelet adhesion (73.6 % red blood cell attachment). Crucially, the modified cotton gauze also exhibits broad-spectrum antibacterial activity (>95 % inhibition against E. coli and S. aureus), addressing the dual demands of hemostasis and infection prevention unmet by conventional cotton dressings. Biosafety assessments confirm clinical viability (<3 % hemolysis, ~90 % cell viability). In vivo studies demonstrate accelerated wound closure through Zn2+-mediated collagen deposition and anti-inflammatory modulation, with the cotton scaffold synergistically enables therapeutic amplification due to its mechanical compliance, breathability and fluid management capabilities.

Chronic non-healing wounds represent a growing global health challenge that is poorly addressed by current advances in wound care dressings. Hyperosmotic stress linked, for example, to poor glycaemic control, is a known but under-investigated contributor to the chronic wound environment and a known inflammatory stimulus. MXene (Ti3C2Tx) has been considered for smart dressing applications but has not been investigated for use with bioactive agents to directly moderate hyperosmotic stress for improved wound care. In this study, Ti3C2Tx, in combination with osmolyte betaine, was used to investigate hyperosmotic stress-induced effects on wound closure. The effect of these materials was measured using a wound closure scratch assay, and data was used to mathematically model changes in HaCaT human keratocyte migratory rate and velocity. Changes in the upregulation of apoptotic and inflammatory markers were measured, and qualitative changes in phalloidin-labelled actin cytoskeletal structure were observed. A tert-butyl glycine betainate (tBu-GB) polyacrylate microgel loaded Ti3C2Tx dressing was then fabricated and tested for biocompatibility and slow elution of osmolyte over time. Osmotic stress at levels that did not induce cell death reduced the migratory capacity of keratocytes to close the scratch. Migration by osmotically stressed keratocytes was reduced by more than 50% at 24 h and remained at 65% (±5%) at 48 h compared to complete scratch closure at 24 h in the cell only control. This reduction was reversed by a Ti3C2Tx coating, allowing complete scratch closure by 48 h in the osmotically stressed group. Exposure of osmotically stressed cells to betaine increased normalised wound closure in the osmotically stressed keraotycte group at each time point and this was augmented by the presence of a Ti3C2Tx coating. Osmotic stress induced upregulation of inflammatory markers IL-6, IL-1α, IL-1β, CXCL1, and CXCL8 by at least 10-fold. The effect was significantly greater in the presence of bacterial LPS and this was significantly reduced by the presence of Ti3C2Tx alone and in combination with betaine. Sustained and slow release of betaine was demonstrated from a tBu-GB-microgel loaded Ti3C2Tx dressing over 48 h supporting the use of such dressings to improve osmotic stress induced, poor wound closure rates.

Stem cell therapy has emerged as a groundbreaking approach in regenerative medicine, offering immense potential for tissue regeneration and wound healing. Stem cells, with their ability to self-renew and differentiate into specialized cell types, provide innovative therapeutic strategies for variety of medical conditions. Key stem cell types, including embryonic, induced pluripotent, and adult stem cells such as mesenchymal and hematopoietic stem cells, play pivotal roles in regenerative processes and wound repair. In tissue regeneration, stem cells replenish damaged or necrotic cells by differentiating into specialized cell types like bone, muscle, or nerve cells, thus restoring the structural and functional integrity of tissues. In wound healing, stem cells stimulate angiogenesis, generate new skin cells, and modulate immune responses to enhance repair. This multifaceted therapeutic potential has paved the way for clinical applications in cardiovascular, neurological, musculoskeletal, and autoimmune disorders, as well as skin and burn injuries. This review highlights recent advancements in stem cell therapy, exploring its clinical applications and addressing challenges such as immune rejection, ethical concerns, scalability, and the need for long-term clinical trials. The article underscores the importance of continued research to fully realize the transformative potential of stem cell therapy in modern medicine.

The dysfunction of wound-healing processes can result in chronic non-healing wounds and pathological scar formation. Current treatment options often fall short, necessitating innovative approaches. Exosomes, extracellular vesicles secreted by various cells, have emerged as promising therapeutic agents serving as an intercellular communication system. By engineering exosomes, their cargo and surface properties can be tailored to enhance therapeutic efficacy and specificity. Engineered exosomes (eExo) are emerging as a favorable tool for treating non-healing wounds and pathological scars. In this review, we delve into the underlying mechanisms of non-healing wounds and pathological scars, outline the current state of engineering strategies, and explore the clinical potential of eExo based on preclinical and clinical studies. In addition, we address the current challenges and future research directions, including standardization, safety and efficacy assessments, and potential immune responses. In conclusion, eExo hold great promise as a novel therapeutic approach for non-healing wounds and non-healing wounds and pathological scars. Further research and clinical trials are warranted to translate preclinical findings into effective clinical treatments.

Diabetic foot ulcers (DFUs) are a devastating complication of diabetes mellitus (DM) that affect millions of people worldwide every year. They have a long-term impact on patients' quality of life and pose a significant challenge for both patients and clinicians, alongside negative economic implications on affected individuals. The current therapeutic approaches are costly and, in many cases, ineffective, highlighting the urgent need to develop novel, affordable, more efficient, and personalized treatments. Recent advances in high-throughput omics technologies, including proteomics, bulk RNA sequencing (bulk RNA-seq), single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics in both preclinical animal and human clinical studies, have enhanced our understanding of the molecular function and mechanisms of DFUs, thereby offering potential for targeted therapies. Additionally, these technologies provide valuable insights behind the mechanism of action of novel wound dressings and treatments. In this review, we outline the latest application of omics technologies in DFU preclinical animal and human clinical research on diabetic wound healing, and spotlight recent findings.A graphical abstract is available with this article.

Necrotizing soft tissue infections (NSTIs) are rapidly progressive, life-threatening infections associated with significant morbidity and mortality. Surgical debridement, the cornerstone of treatment, often results in extensive, complex wounds located in anatomically difficult regions. Management of these wounds can be challenging, especially for surgeons with limited experience in complex wound care and reconstruction. Yet, proper management of these wounds is critical to patient recovery and long-term quality of life. This review provides a comprehensive overview of current strategies in NSTI wound reconstruction. It begins by outlining the biological underpinnings of wound healing and the unique challenges posed by NSTI-related wounds. The review then explores a range of dressing materials and advanced wound care modalities, including negative pressure wound therapy, cellular and tissue-based products, and hyperbaric therapy. Finally, it presents a guide to surgical reconstruction techniques, including skin grafting and flap coverage. By consolidating current knowledge and practical guidance, this review seeks to support generalist and acute care surgeons with the knowledge needed to optimize wound healing, enhance functional outcomes, and improve quality of life for NSTI survivors.

The rapid increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) infections, along with the cross-resistance of CRKP to other antibiotics, has created an urgent need for novel therapeutic agents. Among the potential options for next-generation antibiotics, antimicrobial peptides (AMPs) show great promise. In this study, we aimed to elucidate the mechanisms underlying the antibacterial activity against CRKP of an antibacterial peptide named Cecropin-4 (Cec4), which we successfully identified previously. Our results demonstrate that Cec4 not only exhibits rapid antibacterial activity but also effectively inhibits and eradicates bacterial biofilm at a low concentration of 8 µg/mL. Additionally, when used in combination with traditional antibiotics, Cec4 enhances their antibacterial effect. Microscopy techniques, including transmission electron microscopy (TEM), confocal laser scanning microscopy, and scanning electron microscopy (SEM), found that Cec4 destroyed bacteria's cell membrane integrity and increased the membrane permeability (flow cytometry instrument technology further characterization of Cec4 against K. pneumoniae bacteria antibacterial effect). Furthermore, in vitro experiments demonstrated that Cec4 binds to bacterial DNA and RNA of CRKP. Moreover, in vivo studies using a mouse skin wound model confirmed the efficacy of Cec4, and transcriptomic analysis shed light on the molecular mechanisms underlying its antibacterial activity. Based on our findings, Cec4 appears to be a promising candidate for combating CRKP infections.IMPORTANCEThe rapid increase in carbapenem-resistant Klebsiella pneumoniae (CRKP) infections and the serious cross-resistance to multiple antibiotics make the development of new therapeutic drugs urgent. Antimicrobial peptides (AMPs) have attracted much attention as a potential option for the next generation of antibiotics. Previous studies have identified the antimicrobial peptide Cecropin-4 (Cec4), and this study further explored its antimicrobial mechanism against CRKP. Studies have found that Cec4 shows high antibacterial activity at low concentrations, can inhibit and eradicate bacterial biofilms, and can also enhance the efficacy of traditional antibiotics. Its mechanism of action, such as destroying cell membranes and binding nucleic acid, has been revealed by various techniques, and its effectiveness has been confirmed in vivo, providing a promising candidate drug for combating CRKP infection.

Diabetic foot represents a significant healthcare challenge, accounting for a substantial portion of diabetes-related hospitalizations and amputations globally. The complexity of diabetic foot management stems from the interplay of poor glycemic control, neuropathy, and peripheral vascular disease, which hinder wound healing processes. The high incidence, recurrence, and amputation rates associated with diabetic foot underscore the urgency for innovative treatment strategies. Recent advancements in nanotechnology, particularly the emergence of MXenes (two-dimensional transition metal carbides and/or nitrides), have shown promising potential in addressing these challenges by offering unique physicochemical and biological properties suitable for various biomedical applications. It is a novel potential strategy for diabetic foot wound healing in the future. This review comprehensively summarizes current knowledge, unique characteristics, and underlying mechanisms of MXenes in the context of diabetic foot management. Additionally, we propose the potential application of MXenes-based therapeutic strategies in diabetes foot. Furthermore, we also provide an overview of their current challenges and the future perspectives in related fields of diabetic wound healing.

Numerous efforts have been done to develop wound dressings for effective wound treatment, remains a considerable challenge. The aim of current research work was to prepare multifunctional sodium alginate/thiolated karaya gum hydrogel dressings containing moxifloxacin in combination with artemesia/cedarwood essential oil. Thiolation of karaya gum was achieved by esterification reaction with 3 mercapto-propionic acid and synthesis of blended sodium alginate and thiolated karaya gum hydrogel films without (S1/TK1) and with moxifloxacin and artemesia/cedarwood oil (S1/TK1.DA1, S1/TK1.DC1) was achieved using solvent casting technique and were evaluated for fourier transform infrared spectrum and thermogravimetric analysis. Increasing the concentration of thiolated karaya gum substantially enhanced the bioadhesion, with a 350 % increase in bioadhesion-force and 353 % improvement in bond-strength while exhibiting balanced mechanical properties with an increase rate of 166 % in tensile strength and 73 % in percent-elongation. Incorporation of both moxifloxacin and artemesia/cedarwood oil also considerably enhanced the antibacterial activity of Optimized S1/TK1.DA1 and S1/TK1.DC1 formulations by 286 % and 253 % against s. aureus and 367 % and 269 % against e. coli respectively. Furthermore 2, 2 - di phenyl picryl hydrazyl (DPPH) and superoxide anion scavenging potential of S1/TK1.DA1 and S1/TK1.DC1 were enhanced by 1587 %, 1379 % and by 1384 % and 1245 % respectively. In vivo wound healing efficacy in cutaneous rat model also confirmed almost complete wound closure (≈ 99 %), collagen deposition and anti-inflammatory activity, enabling rapid wound recovery in twelve days. In conclusion, prepared hydrogel dressings might be an outstanding choice for wound healing applications.

Due to poor angiogenesis under the wound bed, wound treatment remains a clinical challenge. Therefore, there is an urgent need for new dressings to combat bacterial infections, accelerate angiogenesis, and accelerate wound healing. In this study, we prepared carbon dots nanomaterial (PF-CDs) derived from traditional Chinese medicine paeoniflorin using a simple green one pot hydrothermal method. The average particle size of the CSs we prepared was 4 nm, and a concentration of 200 μg ml-1was ultimately selected for experiments. Subsequently, PF-CDs were loaded into the chitosan hydrogel to form a new type of wound dressing CSMA@PF-CDs hydrogel. CSMA@PF-CDs demonstrated positive biocompatibility by promoting a 20% increase in cell proliferation and strong antibacterial activity. In comparison to the control group, CSMA@PF-CDs enhanced the expression level of anti-inflammatory factors by at least 2.5 times and reduces the expression level of pro-inflammatory factors by at least 3 times. Furthermore, CSMA@PF-CDs promoted the migration of Human umbilical vein endothelial cells and increased vascular endothelial growth factor expression by 5 times. The results ofin vivoexperiments indicate that CSMA@PF-CDs significantly promoted the healing of back wounds in rats. These characteristics make it a promising material for repairing infected wounds and a potential candidate for clinical skin regeneration applications.

Keratinocytes, the most important cell type constituting the epidermis, migrate to restore the epithelial barrier during wound healing and are a crucial step in wound healing. This study utilized bioinformatics analysis of comprehensive expression datasets of aberrantly expressed genes in wound healing to identify the abnormal expression of the critical transcription factor Fos-like antigen-1 (FOSL1), which is involved in various diseases. Currently, there is limited research on the role of FOSL1 in wound healing, and its molecular mechanisms remain unclear. This study explores the role and regulatory mechanisms of FOSL1 in the wound-healing process. A comprehensive expression dataset of abnormal genes in wound repair was constructed by bioinformatics analysis. Mouse trauma models and mouse wound splint models were constructed to verify the role of FOSL1 in vivo. Real-time quantitative polymerase chain reaction (qRT-PCR), immunoblot, immunofluorescence staining, and HE staining were used to confirm the analysis, and FOSL1 was used as the target in the wound healing process. At the cellular level, using 5'-ethynyl-2'-deoxyuridine (EdU) assay, Transwell assay, Migration assay, western blotting and immunofluorescence, FOSL1 promoted the molecular mechanism of wound repair by regulating the proliferation and migration of keratinocytes through IL-17 signaling pathway. Bioinformatics analysis revealed differential expression of FOSL1 during wound healing. In the mouse back wound model, qRT-PCR, western blotting (WB), and immunofluorescence staining showed significant upregulation of FOSL1 and IL-17 expression during wound tissue healing, indicating a close association between FOSL1 and mouse wound healing. In the mouse wound splinting model, subcutaneous injection of recombinant FOSL1 protein contributed to wound surface healing. Overexpression of FOSL1 in HaCaT cells promoted their proliferation and migration abilities. When IL-17 inhibitor was added to HaCaT cells, both FOSL1 overexpression and knockdown inhibited the proliferation and migration abilities of HaCaT cells. Thus, this study confirms that FOSL1 promotes keratinocyte proliferation and migration through the IL-17 signaling pathway, facilitating wound healing in epidermal wound repair. The results of this study indicate that FOSL1 plays a key role in epidermal wound healing, and elucidate a new molecular mechanism by which FOSL1 promotes keratinocyte proliferation and migration through IL-17 signaling pathway in epidermal wound repair, thereby promoting wound healing.

Background/Objectives: Over the last decade, the development of innovative wound products has continued to be a focus of intense research to meet the huge demand of patients. The aim of this work was to develop novel medicated Spanish broom wound dressings capable of releasing Rosa canina extract, recognized for its high antioxidant activity. Methods:Rosa canina extract was encapsulated in two different nanocarriers, namely glycethosomes and allanthosomes. The physico-chemical and functional characteristics of the obtained vesicles were described, including their size, particle size distribution, ζ potential, and encapsulation efficiency (EE). In addition, vesicles cytotoxicity and cell proliferation were evaluated on human fibroblasts. Furthermore, loaded vesicles were sunk into Spanish broom dressings, analyzed by confocal microscopy, and, finally, evaluated for their wound healing ability by scratch test. Results: Both carriers are nanometric in size, with a good EE (>70%), and a negative ζ potential. Additionally, vesicles are biosafe, non-cytotoxic, and lead to complete closure of the scratch in about 30 h. Conclusions: The findings showed that the developed Spanish broom dressings have the potential to be an efficient and innovative wound care product for accelerating skin wounds.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) are quickly growing in popularity as effective tools in the management of diabetes and weight loss. Despite this increased usage, there is a paucity of literature investigating the use of GLP-1RA in patients with ankle fractures. This study aims to compare the outcomes of patients undergoing ankle fracture open reduction and internal fixation (ORIF) receiving therapy with GLP-1RA to those not receiving treatment. A retrospective analysis was performed utilizing the TriNetX research network to query patients who underwent ankle fracture ORIF between 2000-2024. Two cohorts were established according to preoperative GLP-1RA usage with 1:1 matching by propensity scores for demographics and comorbidities. Primary outcomes included the risk of postoperative complications (i.e. infection, sepsis, wound dehiscence, cellulitis, thrombosis, nonunion, reoperation, revision, etc.) at 30-days, 90-days, 1-year, and 5-years. There were 123,546 patients not taking GLP-1RA and 1,173 patients taking GLP-1RA who underwent ORIF for an ankle fracture, with propensity score matching resulting in two cohorts of 1,173 patients each. After matching, there were no significant differences in demographics or comorbidities, including a 75.6 % prevalence of diabetes mellitus and 68.7 % prevalence of overweight or obesity in both cohorts. At 30-days postoperatively, the no GLP-1RA cohort had a significantly higher rate of removal of hardware (Odds Ratio [OR] 1.953, 95 % Confidence Interval (CI) 1.062-3.591); no other complications demonstrated significant differences at 30-days, 90-days, 1-year, or 5-years postoperatively. These findings further underscore the low risk of preoperative GLP-1RA usage noted in other orthopaedic procedures.

Novel topical nanosponges were implemented to improve the skin availability of simvastatin (SV) for treating full-thickness wounds while controlling the scarring process. SV exhibits great potential in treating various skin diseases owing to its antibacterial, antioxidant, anti-inflammatory, and immunomodulatory properties. However, its poor oral bioavailability and systemic side effects have hindered its clinical application in dermatology. For the first time, nanosponges were utilized to target injured skin, creating an SV reservoir within the wound bed to enhance therapeutic efficacy while minimizing adverse effects. Herein, SV-loaded ethyl-cellulose nanosponges (SV-NS) were prepared using the emulsion solvent evaporation technique, optimizing organic solvents, SV concentration, and stabilizer concentration. The selected SV-NS (20 mg SV) exhibited nanoporous particles (786.2 ± 50 nm), a specific surface area of 10.3 m2/g, and a total pore volume of 0.016 cm3/g, offering sustained release and enhanced skin retention capacity. In vivo studies on full-thickness rat wounds confirmed that topical SV-NS (5 mg SV, applied every 5 days) significantly accelerated wound closure (P < 0.0001), achieving 76.23 ± 3.20% closure by day 8, a 47% improvement over free SV. Consequently, SV-NS facilitated wound closure exceeding 90% by day 11, whereas free SV required 16 days to attain a comparable level, representing a 31.2% faster healing rate. Histological analysis further revealed that SV-NS promoted optimal epidermal layer formation and well-organized collagen deposition, with collagen expression significantly (P < 0.0001) reaching 59.85 ± 3.17% by day 16. Conclusively, SV-NS enhances SV's dermal availability, improving wound healing and minimizing side effects, demonstrating a promising approach for wound restoration.

Wound healing is a highly coordinated biological process encompassing four distinct yet interconnected stages. Notably, microRNA (miRNA) dysregulation is related to non-healing wounds, and miRNAs are considered promising therapeutic targets for wound healing. However, its function and underlying mechanism in wound healing remain incompletely understood. Here, we detected and characterized the miRNA expression patterns during wound healing. Interestingly, miR-301a-5p was significantly downregulated in the initial inflammatory stage and finally peaked in early proliferative phases, suggesting its potential role in modulating phase transition from inflammatory to proliferative phase. Moreover, miR-301a-5p not only promoted the proliferation and migration of macrophages, but also suppressed the excessive inflammatory response, as evidenced by both facilitating the expression of IL-10 and TGF-β and suppressing the pro-inflammatory factors expression. Mechanistically, miR-301a-5p directly targeted inhibitor of κB kinaseβ (IKKβ) and regulated its expression to modulate nuclear factor κB (NF-κB) pathway and macrophage polarization (M1 to M2). Importantly, miR-301a-5p overexpression significantly promoted the regeneration of full-thickness skin wound in mice by regulating NF-κB and macrophage polarization, thereby facilitating epidermal regeneration and collagen deposition. Together, our study found that miR-301a-5p as a novel regulator in the wound healing process transition, and provided potent pro-healing agents for wound healing.

Non-healing chronic wounds with high susceptibility to infection represent a critical challenge in modern healthcare. While growth factors play a pivotal role in regulating chronic wound repair, their therapeutic efficacy is compromised in infected microenvironments. Current wound dressings inadequately address the dual demands of sustained bioactive molecule delivery and robust antimicrobial activity.

In this study, we developed a sodium alginate hydrogel (termed P-SA/Ins), which incorporated polyhexamethylene biguanide (PHMB) grafting and long-acting glargine insulin loading. P-SA/Ins exhibited the favorable physicochemical performance, biocompatibility and antibacterial efficacy against both Gram-negative and Gram-positive pathogens through inhibition of bacterial proliferation and biofilm formation. Glargine insulin was applied to prolonged insulin delivery. P-SA/Ins treatment attenuated S. aureus induced pro-inflammatory cytokine cascades in macrophages. The evaluation in vivo using a rat model with S. aureus infected wound demonstrated that P-SA/Ins significantly enhanced wound healing and optimized skin barrier through antimicrobial-mediated modulation of macrophage polarization and subsequent inflammatory cytokine profiling.

Our findings demonstrate that P-SA/Ins promotes wound healing and restores epidermal barrier integrity, indicating its potential as a therapeutic dressing for chronic wound healing, particularly in cases with infection risk.

Chronic trauma is a prevalent and significant complication of diabetes. Mesenchymal stem cell(MSC)-derived exosomes (Exos) have been reported to accelerate the healing of chronic diabetic wounds. MSCs pretreated with chemical or biological factors were reported to enhance the biological activity of MSC-derived exosomes. Hence, this study investigated the role of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) pretreated with metformin (MET) on diabetic wound healing. The results showed that MET-Exos promoted endothelial cell migration, tube formation, and angiogenesis, leading to accelerated wound healing in diabetic mice. Mechanistically, MET-Exos upregulated LINC-PINT, which, through competitive binding to miR-139-3p, activated FOXC2, a key regulator of angiogenesis. These data reveal that MET-Exos might promote revascularization and wound healing through the LINC-PINT/miR-139-3p/FOXC2 axis, showing its potential as a therapeutic modality for diabetic wounds.

The development of injectable bio-stimulating polycaprolactone (PCL) microspheres for wound healing has strict requirement on size and morphology control, particularly favoring microspheres within the range between 20-50 µm. PCL microspheres with smaller sizes are phagocyted at rapid rate while larger microspheres could cause inflammation. Homogenization can be regarded as an irreversible process to generate microspheres of particular size range while it still remains as the most common approach for microspheres production. Membrane emulsification technology shows great potential in fine tailoring of microspheres while still holds promising ability for scale-up production. Membranes with uniform large pores and dual hydrophilicity might be capable of the production of large microspheres via emulsification with tailorable size distribution. The aim of this study is to verify the feasibility of PVDF membranes with large pores on the generation of PCL microspheres via the combined crystallization diffusion (CCD) approach. The effect of dope solution concentration and PVDF molecular weights on membrane morphologies and the corresponding microspheres characteristics were investigated. Results showed that concentration of 20 wt% produced microspheres at desirable size of 24.14 µm and the optimal span of 0.53. Microspheres with narrow distribution showed the highest drug loading efficiency of baicalin at 8.42 %. The baicalin loaded PCL microspheres presented gradual release of drug release over 33-day of in vitro testing and significantly improved cell growth rate of 111.67 % as compared to the ones prepared by homogenization approach. The wound healing ability was enhanced after the treatment of baicalin-loaded PCL microspheres as compared to empty loaded PCL microspheres.

Diabetic wounds are difficult to heal because of persistent oxidative stress and limited angiogenesis. However, traditional wound dressings cannot address these issues simultaneously. In this study, a thermosensitive chitosan (CS) hydrogel loaded with Thonningianin A (TA) nanoparticles (TA-NPs) was constructed. First, TA-NPs were developed via the nanoprecipitation technique. CS was subsequently combined with β‑sodium glycerophosphate (β-GP) to prepare a thermosensitive hydrogel matrix (CS/β-GP). Finally, composite hydrogels (TA-NPs@Gel) with antioxidant and angiogenesis-promoting properties were synthesized by incorporating TA-NPs into a CS/β-GP hydrogel matrix. Characterization revealed that the TA-NPs were uniformly spherical, with a particle size of 186.30 ± 1.15 nm and a zeta potential of -35.07 ± 0.61 mV. Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed the successful integration of TA-NPs into the hydrogel matrix. Both in vitro and in vivo studies demonstrated that TA-NPs@Gel exhibited potent antioxidant and angiogenic effects, significantly accelerating wound healing in a diabetic mouse model. Network pharmacology predictions indicated that TA-NPs@Gel promoted diabetic wound healing through the HIF-1 signaling pathway. Overall, the integration of TA-NPs into a hydrogel system has broad therapeutic potential for the treatment of diabetic wounds.

Diabetic wounds healing is often severely slowed by hyperglycemia, elevated oxidative stress, bacterial infections, and persistent inflammation. This review focuses on the development of hydrogels derived from carbohydrate polymer and protein to facilitate diabetic wound healing. We discuss the primary sources of cellulose, chitosan, hyaluronic acid, sodium alginate, collagen, and gelatin along with their advantages in the preparation of hydrogels. Based on the microenvironment of diabetic wounds, i.e., hyperglycemia, increased oxidative stress, and persistent inflammation, the application of multifunctional hydrogels in promoting diabetic wounds, including stimulus responsiveness, injection self-healing, antibacterial, antioxidant, anti-inflammatory, and synergistic effects, is discussed. We address the main challenges and future perspectives of multifunctional hydrogels based on carbohydrate polymer and protein in the treatment of diabetic wounds.

Wound healing is a natural, however complex, tissue repair and regeneration mechanism. Understanding the cascade of biological events associated with wound healing facilitates scientists in designing topical skin formulations with enhanced therapeutic outcomes. In recent years, several innovative approaches have been utilized to treat wounds. Hyaluronic acid (HA)-based formulations have shown promising results. The current manuscript provides a systematic review of various aspects of HA, including its structure, synthesis, mechanism involved in wound healing, and various formulations developed using HA to treat wounds. Covered are innovative treatment strategies explicitly emphasizing nanocarrier-based approaches. Various patents wherein HA has been used to treat wounds are also summarized with the help of a Google patent search. Diving deep, clinical perspectives, toxicity aspects, and application of computational chemistry in HA research are also discussed.

Background: Diabetic wound is one of the most common diabetic chronic complications. Effective treatments of diabetic wound remain limited. Here, we explored the effects of basic fibroblast growth factor (bFGF)-acellular dermal matrix (ADM) hydrogel on the diabetic wound. Methods: The bFGF-ADM hydrogel was manufactured by mixing 180 µL ADM hydrogel and 20 µL bFGF aqueous solution (10 mg/mL). The morphology of ADM hydrogel and bFGF-ADM hydrogel was observed under scanning electron microscope. The release property of bFGF-ADM hydrogel was determined by ELISA. CCK-8 assay was utilized to estimate the cell viability of mouse skin fibroblasts. The diabetes mellitus (DM) model was established in rats. The four wounds on the back of each DM rat were treated with the ADM hydrogel, bFGF-ADM hydrogel, bFGF aqueous solution and no solution (control), respectively. The wound healing rate of each rat was estimated. The traumatized skin tissue of each rat was observed by H&E staining and Sirius red staining. Results: The bFGF-ADM hydrogel displayed an interconnected pore structure and bFGF was gradually released from the bFGF-ADM hydrogel over time. The bFGF-ADM hydrogel could enhance the cell viability of skin fibroblasts and promote the wound healing rate, the re-epithelialization of wound and increase the collagen fiber content of dermis. And the bFGF-ADM hydrogel exhibited better therapeutic effects of diabetic wound than either bFGF or ADM alone. Conclusions: Our study revealed that the bFGF-ADM hydrogel could promote diabetic wound healing.

Wound healing is often hindered by hyperglycemia, chronic inflammation and ageing. Despite extensive research on the pathophysiology of hard-to-heal wounds, wound healing remains complex and poses challenges in treatment and management. Current wound treatments and care mostly target a single pathology, such as infection, while most hard-to-heal wounds are multifactorial. Therefore, exploring the factors that do not rely on a single pathology is crucial to fill the gap in current wound management. Despite containing more comprehensive information than commonly used wound tissue samples, cells in the wound fluid have not drawn much attention because of collection difficulties. This study aimed to use single-cell RNA sequencing (scRNA-seq) of cells from wound fluid to identify specific biomarkers for hard-to-heal wounds, with the hypothesis that common biomarkers among various wound models can be potentially applied to complex hard-to-heal wounds in clinical settings. Three representative delayed wound models, aged, diabetic and lipopolysaccharide-induced inflammatory wound models, were compared with normal young mice to explore commonly shared genes that exist in different pathological delayed wound healing models. The shared upregulation of cell cycle and cellular senescence-related genes such as Rpl11, Rpl26, Rps3, Rps15, Rps 20, Rps26, Ccl2, Cdk2ap2 and Ccnd3 and the downregulation of immune response regulation genes such as Tnfaip3, Junb, Il1r2, Plaur, Il1rn, Il1a, Cxcl2, Cd14, S100a8 and S100a9 in all delayed healing wound models were found in most immune cell subgroups, especially the macrophage subgroup. The results of this study suggested cellular senescence of cells in wound fluid could be related to hard-to-heal wounds.

Diabetic wounds present a significant healthcare challenge due to impaired healing mechanisms, with dermal fibroblasts playing a crucial role in tissue repair. This study investigates the role of transient receptor potential canonical-3 (TRPC3) in the dysfunction of diabetic fibroblasts and explores the therapeutic potential of TRPC3 inhibition. Findings reveal that TRPC3 expression is significantly elevated in diabetic dermal fibroblasts, which correlates with suppressed transforming growth factor-beta (TGF-β) signaling and impaired differentiation into myofibroblasts. Inhibiting TRPC3 effectively restores fibroblast functionality by upregulating TGF-β1 and its downstream effector, SMAD4. This restoration enhances the expression of key myofibroblast markers, such as α-smooth muscle actin (ACTA2) and type I collagen (COL1a1), which are essential for wound contraction and extracellular matrix remodeling. These results establish TRPC3 as a critical regulator of fibroblast activity and present TRPC3 inhibition as a promising therapeutic strategy for improving wound healing in diabetic patients.

Significance: Nonhealing or chronic wounds represent a significant and growing global health concern, imposing substantial burdens on individuals, health care systems, and economies worldwide. Although the standard-of-care treatment involves the application of wound dressings, most dressing materials are not specifically designed to address the pathological processes underlying chronic wounds. This review highlights recent advances in biomaterial design tailored to chronic wound healing. Recent Advances: Chronic wounds are characterized by persistent inflammation, impaired granulation tissue formation, and delayed re-epithelialization. Newly developed designer materials aim to manage reactive oxygen species and extracellular matrix degradation to suppress inflammation while promoting vascularization, cell proliferation, and epithelial migration to accelerate tissue repair. Critical Issues: Designing optimal materials for chronic wounds remains challenging due to the diverse etiology and a multitude of pathological mechanisms underlying chronic wound healing. While designer materials can target specific aberrations, designing a materials approach that restores all aberrant wound-healing processes remains the Holy Grail. Addressing these issues requires a deep understanding of how cells interact with the materials and the complex etiology of chronic wounds. Future Directions: New material approaches that target wound mechanics and senescence to improve chronic wound closure are under development. Layered materials combining the best properties of the approaches discussed in this review will pave the way for designer materials optimized for chronic wound healing.

Platelet-rich plasma (PRP) is a blood product with higher platelet concentrations than whole blood, offering controlled delivery of growth factors (GFs) for regenerative medicine. PRP plays pivotal roles in tissue restoration mechanisms, including angiogenesis, fibroblast proliferation, and extracellular matrix development, making it applicable across various regenerative medicine treatments. Despite promising results in different tissue injuries, challenges such as short half-life and rapid deactivation by proteases persist. To address these challenges, biomaterial-based delivery scaffolds, such as sponges or hydrogels, have been investigated. Current studies exhibit that PRP-loaded scaffolds fix these issues due to the sustained release of GFs. In this regard, given the widespread application of PRP in clinical studies, the use of PRP-loaded scaffolds has drawn significant consideration in tissue engineering (TE). Therefore, this review briefly introduces PRP as a rich origin of GFs, its classification, and preparation methods and discusses PRP applications in regenerative medicine. This study also emphasizes and reviews the latest research on the using scaffolds for PRP delivery in diverse fields of TE, including skin, bone, and cartilage repair.

Light-based biofabrication techniques have revolutionized the field of tissue engineering and regenerative medicine. Specifically, the projection of structured light, where the spatial distribution of light is controlled at both macro and microscale, has enabled precise fabrication of complex three dimensional structures with high resolution and speed. However, despite tremendous progress, biofabrication processes are mostly limited to benchtop devices which limit the flexibility in terms of where the fabrication can occur. Here, a Fiber-assisted Structured Light (FaSt-Light) projection apparatus for rapid in situ crosslinking of photoresins is demonstrated. This approach uses image-guide fiber bundles which can project bespoke images at multiple wavelengths, enabling flexibility and spatial control of different photoinitiation systems and crosslinking chemistries and also the location of fabrication. Coupling of different sizes of fibers and different lenses attached to the fibers to project small (several mm) or large (several cm) images for material crosslinking is demonstrated. FaSt-Light allows control over the cross-section of the crosslinked resins and enables the introduction of microfilaments which can further guide cellular infiltration, differentiation, and anisotropic matrix production. The proposed approach can lead to a new range of in situ biofabrication techniques which improve the translational potential of photofabricated tissues and grafts.

This study aimed to optimize the extraction of phytocompounds intended for wound care applications from three plant species, Sambucus nigra L. flowers and Epilobium hirsutum L. and Lythrum salicaria L. aerial parts, by using a Quality by Design approach. The effects of different extraction methods (ultra-turrax and ultrasonic-assisted extraction), ethanol concentrations (30%, 50%, 70%), and extraction times (3, 5, 10 min) were studied, and during the optimization step, the polyphenol and flavonoid contents were maximized. The phytochemical profiles of the optimized HEs (herbal extracts) were assessed using LC-MS/MS methods. The antioxidant capacity of the optimized HEs was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity) TEAC (Trolox equivalent antioxidant capacity), and FRAP (ferric reducing antioxidant power) assays, while the antibacterial activity was evaluated against Escherichia coli, Pseudomonas aeruginosa, and MSSA-methicillin-sensitive Staphylococcus aureus and MRSA-methicillin-resistant Staphylococcus aureus). Cell viability and antioxidant and wound healing potential were assessed on keratinocytes and fibroblasts. The anti-inflammatory effect was assessed on fibroblasts by measuring levels of interleukins IL-6 and IL-8 and the production of nitric oxide from RAW 264.7 cells. The major compounds of the optimized HEs were rutin and chlorogenic acid. The Lythrum salicaria optimized HE showed the strongest antibacterial activity, while the Sambucus nigra optimized HE demonstrated high cell viability. Lythrum salicaria and Epilobium hirsutum optimized HEs showed increased antioxidant capacities. All extracts displayed anti-inflammatory effects, and the Epilobium hirsutum optimized HE exhibited the best in vitro wound-healing effect.

Diabetes, both Type 1 and Type 2, often leads to chronic wounds due to impaired healing processes, marked by prolonged inflammation, delayed blood vessel formation, and abnormal collagen production. These issues disrupt normal tissue regeneration, slowing healing. To address these challenges, polymer-based wound dressings are being explored as a promising solution. Natural polymers like alginate, chitosan, and hyaluronic acid, as well as synthetic ones like PCL, PLA, and PLGA, offer potential for more effective healing. These materials can be used in advanced delivery systems, such as nanofibrous scaffolds, nanoparticles, and hydrogels, which help deliver medications, maintain a moist healing environment, and stimulate cell growth. By improving the wound environment, polymer-based systems provide new hope for diabetic patients with slow-to-heal wounds, enhancing therapeutic outcomes and accelerating healing. These innovations could significantly improve the management of chronic wounds in diabetes.

While the literature on molecular and clinical effects of smoking on the lungs and other organs has been expansively reviewed, there is no comprehensive compilation of the effects of smoking on stem cell (SC) populations. Recent research has shown that tobacco exposure severely compromises the function of SC populations, particularly those involved in tissue regeneration: mesenchymal SCs (MSCs), neural progenitors, and hematopoietic SCs. SC-based therapies have emerged as a promising approach to counteract smoking-related damage. In particular, MSCs have been extensively studied for their immunomodulatory properties, demonstrating the ability to repair damaged tissues, reduce inflammation, and slow disease progression in conditions such as chronic obstructive pulmonary disease. Combination therapies, which integrate pharmaceuticals with SC treatments, have shown potential in enhancing regenerative outcomes. This review examines the impact of smoking on SC biology, describes the processes impairing SC-mediated repair mechanisms and highlights recent advancements in SC-based therapies in the treatment of smoking-induced diseases. This review has two prongs: (1) it attempts to explain potential smoking-related disease etiology, and (2) it addresses a gap in the literature on SC-mediated repair mechanisms in chronic smokers.