Excisional Wounds Research Articles

Amoeba-Inspired Soft Robot for Integrated Tumor/Infection Therapy and Painless Postoperative Drainage.

Tumor recurrence and wound infection are devastating complications of wide excision surgery for melanoma, and deep postoperative wound drainage typically increases pain. An amoeba-inspired magnetic soft robot (ASR) with switchable dormant and active phases is developed to address the aforementioned challenges. The dormant ASR supports wounds through its solid-like elasticity and regulates reactive oxygen species (ROS) levels bidirectionally, promoting healing in infected wounds and eliminating residual tumors. It solves the challenge caused by the contradictory need for ROS scavenging in wound healing and ROS amplification in tumor/infection management. The active ASR removes absorbed wound exudate by crawling out from irregular wounds; interestingly, this crawling motion prevents damage to fragile tissues and alleviates wound pain via "non-direct friction." More importantly, ASR switches different states in response to an alternating magnetic field owing to its magnetothermal properties, and this process also exerts synergistic antitumor and bacteriostatic effects. Due to the appropriate mechanical structure (cohesive force) of ASR, the content of magnetic nanoparticles required to drive the ASR is ten-fold lower than that of conventional magnetic soft robots, enabling in vivo degradation. These outcomes highlight the vantage of the ASR for treating post-tumor excision wounds and underscore their potential for clinical application.

Tissue nano-transfection of antimicrobial genes drives bacterial biofilm killing in wounds and is potentially mediated by extracellular vesicles

The emergence of bacteria that are resistant to antibiotics is on track to become a major global health crisis. Therefore, there is an urgent need for new treatment options. Here, we studied the implementation of tissue-nanotransfection (TNT) to treat Staphylococcus aureus-infected wounds by delivering gene cargos that boost the levels of naturally produced antimicrobial peptides. The Cathelicidin Antimicrobial Peptide gene (CAMP), which produces the antimicrobial peptide LL-37, was used as model gene cargo. In vitro evaluation showed successful transfection and an increase in the transcription and translation of CAMP-coding plasmid in mouse primary epithelial cells. Moreover, we found that the extracellular vesicles (EVs) derived from the transfected cells (in vitro and in vivo) carried significantly higher concentrations of CAMP transcripts and LL-37 peptide compared to control EVs, possibly mediating the trafficking of the antimicrobial contents to other neighboring cells. The TNT platform was then used in vivo on an excisional wound model in mice to nanotransfect the CAMP-coding plasmid on the edge of infected wounds. After 4 days of daily treatment, we observed a significant decrease in the bacterial load in the CAMP-treated group compared to the sham group. Moreover, histological analysis and bacterial load quantification also revealed that TNT of CAMP on S. aureus-infected wounds was effective in treating biofilm progression by reducing the bacterial load. Lastly, we observed a significant increase in macrophage recruitment to the infected tissue, a robust increase in vascularization, as well as and an increased expression of IL10 and Fli1. Our results demonstrate that TNT-based delivery of gene cargos coding for antimicrobial compounds to the wound is a promising approach for combating biofilm infections in wounds.

Barks of Dacryodes Kukachkana presents antiinflammatory effect in rat cutaneous wounds

Background: Dacryodes kukachkana (Burseraceae) is found in the Amazon rainforest of Brazil, being the genera widely used in folk medicine for several inflammatory conditions. Objective: In this study, it was investigated the anti-inflammatory effect of the Hydroethanolic Extract of D. kukachkana (HEDk) barks in the rat model of excisional skin wounds. Methods: The wounds were induced on the dorsal region of Wistar rats and treated daily by topical application of HEDk (500 mg/100 μL), compared to the control Saline (0.9% NaCl). Clinical parameters (edema, hyperemia, exudate, hypernociception), histopathological (leukocyte infiltrate, fibroblasts, blood vessels) and oxidative stress markers were evaluated from the 2nd to the 6th day post-ulceration. Results: HEDk reduced the following parameters at the 2nd day: inflammatory exudate (0 [0-0] vs. saline: 2 [1 – 3]); wound area (36%), healing index (48.56% ± 1.886 vs. saline: 27.99% ± 2.460) and malondialdehyde (27%). HEDk also reduced leukocyte infiltrate (49 – 34%) from the 4th to the 6th days post-ulceration. HEDk increased the parameters: nociceptive threshold (31 – 73%) from the 2nd to the 4th days; blood vessels (1.9x) and reduced glutathione (32%) at the 4th day; and the number of fibroblasts (91 – 44%) at the 2nd and 6th days. Conclusion: HEDk accelerates the healing process in the rat model of excisional cutaneous wounds via attenuation of inflammatory parameters and stimulation of fibroplasia and angiogenesis.

Wound Healing Activity of Hydroalcoholic Extracts of Lycopersicon Esculentum Seeds and Ficus Racemosa on Wistar Rats

In the Present study Investigation on the preliminary phytochemicals screening of ethanolic extract showed the presence of Resin, Protin, Quinones, Anthraquinon, Carbohydrates, Alkaloids, Glycoside, Steroids, and Phenols. By ethanol extract using standardized procedure and also subjected to wound healing activity exhibited significant wound healing activity with respect to control biological effects of its extracts ointment, mainly the ones related to wound process. The present data clearly showed that the extract of dried Seeds of Lycoperscon esculentum seeds and Ficus racemosa has wound healing activity the highly significant response of some extracts .The result obtained from the excision wound model, Effect of EECG on Percentage Wound Contraction and Epithelialization Period. During the course of treatment the extract was found to show its preliminary effect from day 4 up to day 16.

Gallic acid functionalized silk fibroin/gelatin composite wound dressing for enhanced wound healing.

ABSTRACT
As the incidence of chronic wounds increases, the requirements for wound dressings are rising. The specific aim of this study is to propose a novel gallic acid (GA) functionalized silk fibroin (SF) and gelatin (Gel) composite wound dressing in which GA is used as an antibacterial and wound healing substance. Via electrospinning, SF, Gel, and GA mixed solutions could be conveniently fabricated into a composite nanofiber mat (SF-Gel-GA), consisting of uniform fibers with an average diameter around 134.57 ± 84 nm. The internal mesh structure of SF-Gel-GA provides sufficient drug loading capacity, proper moisture permeability, and proper degradation rate. SF-Gel-GA presents excellent biocompatibility. NIH-3T3 fibroblast cells could adhere and spread stably on the SF-Gel-GA surface with slightly promoted proliferation. In the presence of SF-Gel-GA, the growth of both Gram-positive and Gram-negative bacteria, including Staphylococcus aureusand Pseudomonas aeruginosa, is significantly inhibited in both plate and suspension cultures. A cutaneous excisional mouse wound model proves the efficient ability of SF-Gel-GA to promote wound healing. Compared with pure SF dressing and commercial Tegaderm Hydrocolloid3M dressing, the wound closure rate with SF-Gel-GA treatment is significantly improved. The histological assessments further demonstrate SF-Gel-GA could facilitate collagen deposition, neovascularization, and epithelialization at wound sites to promote wound healing. In conclusion, a novel SF-Gel-GA composite wound dressing with efficient wound healing activities have been developed for chronic wound treatment with broad healing potential.

Histomorphometric analysis of excisional cutaneous wounds with different diameters in an animal model.

The skin wound model in rats is a fundamental stage in preclinical trials, but there is a lack of standardization in these trials regarding the initial wound area, making analysis and comparison between studies difficult. Therefore, this study evaluates the healing progression of excisional skin lesions of varying diameters in Wistar rats, aiming to identify the optimal wound size for monitoring treatment effects on wound healing. Excisions of 0.8, 1.5, 2.0 and 3.0 cm in diameter were made on the back of the animals. Thirty animals were used per treatment and evaluated on days 3, 7, 10, 14 and 21 after surgery. The lesions were cleaned daily with saline solution until they were completely closed. The 0.8 cm group showed complete repair on D14, while in the other groups, the wounds persisted until day 21, with a reddened surface and no complete epidermal coverage, but with greater keratinization and presence of appendages in the 1.5 cm lesions. Therefore, as a standardization model for creating skin wounds, we suggest using 1.5 or 2.0 cm excisions, considering that 0.8 cm wounds close very early and 3.0 cm wounds, although behaving similarly to 2.0 cm wounds, are more invasive for the animals. The 1.5 cm model proved to be suitable for closure within 21 days. When evaluating a product intended to accelerate wound healing, 2.0 cm lesions are recommended to assess the effectiveness of the treatment.

Wound Healing, Anti-Inflammatory and Anti-Oxidant Activities, and Chemical Composition of Korean Propolis from Different Sources

Propolis, such as is used as bio-cosmetics and in functional materials, is increasing because of its antioxidant medicinal benefits. However, its pharmacological and chemical composition is highly variable, relative to its geography and botanical origins. Comparative studies on three propolis samples collected from different regions in Korea have been essential for linking its provenance, chemical composition, and biological activity, thereby ensuring the efficient utilization of its beneficial properties. Here, we report the chemical composition and biological activities such as the antioxidant, wound healing, and anti-inflammatory effects of the ethanolic extract of Korean propolis collected from two regions. We compared the chemical constituents of three 70% ethanol-extracted (EE) samples, including the Andong, Gongju field (GF), and Gongju mountain (GM)-sourced propolis using Gas chromatography–mass spectrometry (GC–MS). The major and common components of these EE Korean propolis were flavonoids such as pinocembrin (12.0–17.7%), chrysin (5.2–6.8%), and apigenin (5.30–5.84%). The antioxidant property using a 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay of EEP showed substantial differences among samples with the highest from Andong. The sample 10% GM levigated in simple ointment was found to be the most active in wound healing activity based on the excision, incision, and dead space wound models. The potential of propolis for wound healing is mainly due to its evidenced properties, such as its antimicrobial, anti-inflammatory, analgesic, and angiogenesis promoter effects, which need further study. The anti-inflammatory activity and NO production inhibitory effect were highest in GM samples. However, GM and GF samples demonstrated similar inhibitory effects on the expression of inflammatory mediators such as iNOS, IL-1β, and IL-6. The presence of a higher concentration of flavonoids in Korean EE propolis might be responsible for their promising wound healing, anti-inflammatory, and antioxidant properties.

Wound healing activity of Ipomoea staphylina leaves extract in Wistar rats

Wound repair is the practice of repairing the skin and other soft tissues after an injury. An inflammatory response is activated after an injury, and cells below the dermis (deepest skin layer) begin to produce more collagen (connective tissue). A scientific assessment was made for the wound-healing potential of Ipomoea staphylina leaves extract, using ethanol. The crude extract was made into a 2.5% and 5% (w/w) ointment and tested for wound healing activity in Wistar rats using excision and incision wound models. In the excision wound model, the period of epithelialization was reduced and an increase in wound contraction rate was observed in the extract treated groups (III and IV). On the tenth day, tissue from the excision wound area was taken and processed for the assessment of pro-inflammatory cytokines (TNF-α), and it was found that there was a notable decrease in the TNF-α concentration in the extract-treated animals. In an incision wound model, the breaking strength was significantly increased in animals treated with 2.5% and 5% (w/w) ointment of I. staphylina leaves extract. The extract significantly promoted fibroblast migration in an in vitro experiment (scratch assay), which may have been caused by the presence of flavonoids.

Deciphering the Wound-Healing Potential of Collagen Peptides and the Molecular Mechanisms: A Review.

Collagen peptides have been reported to display various bioactivities and high bioavailability. Recently, increasing evidence has revealed the excellent wound-healing activity of collagen peptides, but their molecular mechanisms remain incompletely elucidated. This review systematically evaluates the therapeutic efficacy of collagen peptides from diverse sources based on various wound models. Furthermore, the structure-activity relationships of collagen peptides and wound-healing mechanisms are discussed and summarized. Characterized by their low molecular weight and abundant imino acids, collagen peptides facilitate efficient absorption by the body to deliver nutrition throughout the wound-healing process. The specific mechanism of collagen peptide for wound healing is mainly through up-regulation of related cytokines and participation in the activation of relevant signaling pathways, such as TGF-β/Smad and PI3K/Akt/mTOR, which can promote cell proliferation, angiogenesis, collagen synthesis and deposition, re-epithelialization, and ECM remodeling, ultimately achieving the effect of wound healing. Collagen peptides can offer a potential therapeutic approach for treating incision and excision wounds, mucosal injuries, burn wounds, and pressure ulcers, improving the efficiency of wound healing by about 10%-30%. The present review contributes to understanding of the wound-healing potential of collagen peptides and the underlying molecular mechanisms.

Evaluation of the Antioxidant and Healing Properties of the Hydroethanolic Extract of Kalanchoe pinnata (Lam) Pers of the Togolese Flora

Natural herbal remedies have always been important in the management of skin disorders and the treatment of skin infections due to limited access to pharmaceuticals and the affordable cost of herbal products. K. Pinnata is a plant used as a medicinal herb by almost all traditional medicines in tropical Africa. The aim of the present work is to evaluate the antioxidant and healing properties of K. pinnata (Lam) pers extract from Togolese flora. The hydroethanol extract of K. pinnata (Lam) pers was subjected to in vitro antioxidant activity screening models, such as molybdate reduction, iron reduction assay (FRAP) and DPPH radical scavenging assay. A 1.5 cm diameter excision wound model was also used to assess the plant's healing activity. Wistar rats were treated after excision by topical application of vaseline, vaseline supplemented with 3% (EHKP 3%) and 10% (EHKP 10%) hydroethanol extract of K. pinnata (Lam) pers leaves, sulfadiazine (reference), or no treatment (negative control). Total antioxidant activity by the molybdate reduction method was 0.12 ± 0.01 µg EAA/mg EL, while the iron reduction assay (FRAP) showed an antioxidant capacity of 4.21 ± 0.04 mol Eq FeS04/ g extract and 10.17 ± 0.03 mol Eq FeS04/ g extract respectively for extract concentrations of 100 µg/ml and 200 µg/ml. In addition, the extract showed a dose-dependent ability to trap the DPPH radical. Results showed a significant reduction in wound surface area in animals treated with 10% EHKP. The hydroxyproline assay showed a significant difference in collagen production in animals treated with 10% EHKP, compared with the control group (P < 0.001) and the vaseline group (P < 0.01) on the last day. Histological analysis showed rapid re-epithelialization in animals treated with the extracts. Keywords: K. pinnata, Antioxidant activity, Healing activity, Hydroxyproline

Isoorientin Improves Excisional Skin Wound Healing in Mice

Background/Objectives: Wound healing relies on a coordinated process with the participation of different mediators. Natural products are a source of active compounds with healing potential. Isoorientin is a natural flavone recognized as having several pharmacological properties, such as anti-inflammatory effects, making it a potential treatment for wounds. We investigated the effect of isoorientin on the healing of excisional skin wounds. Methods: Male Swiss mice were subjected to the induction of excisional skin wounds (6 mm diameter) and treated with a vehicle (2% dimethyl sulfoxide in propylene glycol) or 2.5% isoorientin applied topically once a day for 14 days. The wound area was measured on days 0, 3, 7, and 14. Histopathological analyses were performed on the cicatricial tissue after 14 days. The myeloperoxidase activity and the interleukin-1β, tumoral necrosis factor (TNF)-α, and interleukin-6 concentrations were determined on the third day. Results: We observed that 3 days after the topical application of isoorientin, the lesion area was significantly smaller when compared to those of the vehicle (p < 0.01) and control (p < 0.05) groups. No difference was observed after 7 and 14 days of induction. Despite this, on day 14, histological analysis of cicatricial tissue from the animals treated with isoorientin showed reduced epidermal thickness (p < 0.001) and increased collagen deposition (p < 0.001). These effects were accompanied by decreased myeloperoxidase activity and interleukin-1β concentration on the third day of induction, without alteration in TNF-α and interleukin-6. Conclusions: The treatment with isoorientin promoted better tissue repair in excisional wounds in mice, which may be linked to the modulation of the early inflammatory response.

An injectable hydrogel of porcine cholecyst extracellular matrix for accelerated wound healing.

Hydrogel formulations of xenogeneic extracellular matrices have been widely used for topical wound care because of their exceptional tunability over other formulations like lyophilized sheets, powders, non-injectable gels, pastes, and ointments. This is important in the treatment of wounds with irregular shapes and depth. This study identified an injectable hydrogel formulation of porcine cholecyst extracellular matrix (60%) in medical-grade carboxymethyl cellulose (40%) as vehicle and evaluated its biomaterial properties. Further, an in-depth evaluation of in vivo wound healing efficacy was conducted in a rat full-thickness skin excision wound healing model, which revealed that the hydrogel formulation accelerated wound healing process compared to wounds treated with a commercial formulation and untreated wounds. The hydrogel appeared to have promoted a desirable pro-regenerative tissue reaction predominated by Th2 helper lymphocytes and M2 macrophages as well as an effective collagen remodeling indicative of diminished scarring. In conclusion, the porcine cholecyst extracellular matrix injectable hydrogel formulation appeared to be a promising candidate formulation as an advanced wound care biomaterial for faster healing of skin wounds with minimal scarring.

Immortelle Essential-Oil-Enriched Hydrogel for Diabetic Wound Repair: Development, Characterization, and In Vivo Efficacy Assessment

Background: Alarming data revealed that 19% to 34% of adults with diabetes mellitus develop chronic wounds, which are characterized by impaired healing and a higher risk of infections. Inspired by the traditional use of immortelle for wound healing and the lack of scientific evidence regarding how it thoroughly influences tissue regeneration, we aimed to formulate a hydrogel loaded with immortelle essential oil and assess its effectiveness on diabetic excision wounds. Methods: The rheological properties of the hydrogel, an in vivo safety test, as well as wound healing capacity, were determined in rats with induced diabetes and excision wounds. Diabetic rats were divided into four groups: untreated, treated with 1% silver sulfadiazine ointment, treated with a gel base, and treated with the immortelle essential oil-based hydrogel. Results: It was revealed that the hydrogel exerts pseudoplastic behavior and has no potential to act as an irritant, thus highlighting its suitability for skin application. Moreover, analysis of macroscopic, biochemical, and histopathological data revealed that the immortelle essential oil-based hydrogel significantly improves wound repair. Superior re-epithelialization, scar maturation, and increased collagen fiber density were achieved after immortelle essential oil-based gel application. Conclusions: These findings suggest that the immortelle essential oil-based hydrogel could be a natural, safe, and effective wound-healing dressing.

A NOVEL WOUND DRESSING WITH SILKWORM COCOON SCAFFOLD TO FASTEN WOUND HEALING: AN IN VIVO STUDY USING RAT EXCISION WOUND MODEL

Objective: The study aimed to compare the effectiveness of silver-nano laden silkworm cocoon scaffold (SWCS), L-Ascorbic acid laden SWCS (AA-SWCS) over standard wet collagen sheet used for wound healing in rat incision wound model. Methods: A total of 24 Wistar rats (of either sex, pathogen free, 10–12 weeks old) were used in this study. SWCS was prepared and an excision wound model was carried out to study the wound healing capacity in four study groups. Dressings were made with silver nanoparticles SWCS (AgNP-SWCS), AA-SWCS and compared with wet collagen sheet regularly. Friedman’s test was used for analysis. Results: The results clearly indicate that both AgNP-SWCS and AA-SWCS significantly accelerate wound healing compared to the standard wet collagen sheet. The AgNP-SWCS outperformed the others in terms of wound contraction rate, histological quality of healing, and microbial load reduction. The AA-SWCS also showed enhanced healing properties, particularly in collagen synthesis and tissue organization. Conclusion: The study suggests that both AgNP-SWCS and AA-SWCS are highly effective alternatives to traditional collagen dressings for wound healing. These innovative scaffolds could represent a new frontier in wound care, providing enhanced healing rates, improved tissue quality, and reduced infection risks, ultimately leading to better patient outcomes.

Inhibition of Ubiquitin C-Terminal Hydrolase L1 Facilitates Cutaneous Wound Healing via Activating TGF-β/Smad Signalling Pathway in Fibroblasts.

Ubiquitin C-terminal hydrolase L1 (UCHL1) plays vital roles in cell proliferation, angiogenesis, inflammation and oxidative stress. Nevertheless, it is unclear whether UCHL1 could regulate the biologic behaviour of cells and ultimately influences wound healing. We aim to illustrate the roles and the underlying mechanism of UCHL1 in cutaneous wound healing. Murine full-thickness excisional wound model was utilised to study the effects of UCHL1 on wound healing through topical administration of the UCHL1 inhibitor LDN57444, followed by assessment of wound areas and histological alterations. Subsequently, ethynyldeoxyuridine, scratch and transwell assays were performed to examine fibroblast migration and proliferation. The extracellular matrix (ECM)-related genes expression and transforming growth factor-β (TGF-β)/Smad signalling pathways activation were investigated by immuno-fluorescent staining, Western blots and quantitative reverse transcription polymerase chain reaction. We identified elevated UCHL1 expression in non-healing wound tissues. The UCHL1 expression displayed a dynamic change and reached a peak on Day-7 post-wounding during the healing process in mice. Cutaneous administration of LDN57444 promoted wound healing by facilitating collagen deposition, myofibroblast activation and angiogenesis. Invitro experiments demonstrated that UCHL1 concentration dependently inhibited migration, ECM synthesis and activation of human dermal fibroblasts, which was mechanistically related to downregulation of TGF-β/Smad signalling. Furthermore, these effects could be reversed by TGF-β inhibitor SB431542. Our findings reveal that UCHL1 is a negative regulator of cutaneous wound healing and considered as a novel prospective therapeutic target for effective wound healing.

Orthoplastic Management of Lower Limb Traumas: A Retrospective Study on Polytraumas Versus Isolated Injuries.

Open fractures of the lower limb represent a common challenge for trauma centers. Even where national guidelines are available, these standards are frequently missing. Our study evaluates the influence of polytrauma on the adherence to the timing and management required in an orthoplastic approach. A retrospective review was performed on 36 patients affected by a Gustilo-Anderson grade IIIA, IIIB, or IIIC fracture of the lower limb between 2018 and 2022. Data related to patient management were analyzed: time to the first evaluation by a plastic surgeon, time to soft tissue coverage, time to definitive osteosynthesis, days in intensive care unit (ICU), days of hospitalization, and total cost of hospital stay. Patient satisfaction was evaluated through the administration of 2 questionnaires: the Enneking and the Foot Function Index (FFI). In 23 patients (63.9%), a soft tissue reconstruction was required. Of these, 13 were polytraumas (PT) (56.5%) and 10 were affected by an isolated lower limb fracture (ILLF) (43.5%). The median time to wound excision was 7.0 days (IQR, 0-16.0) in the PT group and 12.5 days (IQR, 1-41.0) in the ILLF group, whereas the mean time to soft tissue coverage was 15.0 days (IQR, 4.0-17.0) in the PT group and 38.0 days (IQR, 25.0-65.0) in the ILLF group. Mean time to definitive fixation was 33.0 days (IQR, 6.5-70.0) in the PT group and 16.5 days (IQR, 3.0-26.0) in the ILLF group. Statistically significant difference was reported on mean time to soft tissue coverage, whereas not relevant differences were reported on mean time to plastic surgeon involvement, first debridement, definitive fixation, days of hospitalization, costs, and Enneking and FFI score. This is the first study comparing the effectiveness of the orthoplastic approach between isolated lower limb fractures and polytraumas. According to our study, open lower limb fracture management is paradoxically more effective in polytraumas rather than in isolated injuries because a multidisciplinary approach is mandatory in severely injured and compromised patients.

Histological study on the effect of different concentrations of adipose derived stem cells in enhancing wound healing of excisional skin wounds in adult albino rats

Histological study on the effect of different concentrations of adipose derived stem cells in enhancing wound healing of excisional skin wounds in adult albino rats

Development and Characterization of Gingerol-Assisted Silver Nanoparticle and Chitosan Alginate Membrane for Antibacterial and Wound Healing Activity.

This study synthesized and characterized gingerol-loaded silver nanoparticles (Ag-NPs), which were incorporated into chitosan-alginate (Cs/Alg) films for advanced wound care applications. Gingerol was isolated with a 9.81% yield, forming pale-yellow needle-shaped crystals with a melting point of 32ºC. The purity and structure of gingerol were confirmed through thin-layer chromatography (TLC), UV-visible, fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) analyses. The synthesized Ag-NPs, particularly from the GN3 batch, exhibited a small particle size (36.52 ± 3.52 nm), high stability (zeta potential of -23.20 mV), and notable encapsulation efficiency (76.35%) and yield (74.11%). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses revealed their spherical and smooth morphology. Stability tests over three months showed no substantial changes in particle size, ZP, or %EE. The Cs/Alg films demonstrated appropriate thickness, weight, water uptake, and pH changes, with GN-CM4 showing the best performance. In-vitro drug release studies indicated increased release rates, especially for GN-CM4, which also exhibited the highest antibacterial activity. In-vivo studies on excision and burn wound models showed that GN-CM4 promoted complete wound closure by day 21, enhanced hydroxyproline levels, reduced myeloperoxidase content, and facilitated superior tissue regeneration. These findings underscore the potential of gingerol-loaded Ag-NPs in enhancing wound healing through their anti-inflammatory and antibacterial properties.

Antibacterial and Healing Efficacy of Mangiferin-Loaded Silver Nanoparticle and Chitosan-Alginate Membrane Dressings

Mangiferin, a bioactive constituent of Mangifera indica (family Anacardiaceae), has an impressive therapeutic profile, having antioxidant, anti-inflammatory, analgesic, antibacterial, and immunomodulatory properties capable of possessing wound healing potential. Our investigation aims to isolate and characterize mangiferin, green synthesis of silver nanoparticles (Ag-NPs) and production of chitosan alginate (Cs/Alg) film dressing loaded with mangiferin Ag-NPs and assess antibacterial and wound-healing properties against infected excision and burn wounds. The isolated mangiferin was authenticated by estimating melting point, thin layer chromatography (TLC), fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC). Ag-NPs were green synthesized and characterized by UV-visible, particle size, zeta potential (ZP), entrapment efficiency (%EE), scanning electron microscope (SEM), transmission electron microscope (TEM), and stability study. Chitosan alginate membrane dressing was prepared by incorporating mangiferin Ag-NPs, and film thickness, pH, film weight, water intake capacity, and in-vitro drug release parameters were estimated. Among the four mangiferin Ag-NP batches, MN3 formed stable polydispersity spherical Ag-NPs with smaller particle size and high %EE. Mangiferin-loaded Cs/Alg film MN-CM4 showed significantly higher (p < 0.001) drug content, wettability, release profile, and favorable pH changes. The mangiferin Ag-NPs embedded Cs/Alg film dressing showed a significantly high antimicrobial effect against the gram-positive bacterial strain of S. aureus, commonly found in wounds. MN3 and MN-CM4 treatment showed the shortest epithelialization period and enhanced wound closure. The hydroxyproline content has significantly (p < 0.001) increased, and myeloperoxidase content was reduced by MN3 and MN-CM4 treatment. MN-CM4 treatment showed complete re-epithelialization reduced inflammatory cells with thicker and denser collagen fiber deposition. The effectiveness of the Cs/Alg film of mangiferin Ag-NPs dressing has a synergistic effect on promoting speedy wound healing. The Cs/Alg film of mangiferin Ag-NPs showed rapid wound healing against infected and burned wounds, enhanced collagen synthesis, and anti-inflammatory and antibacterial efficacy.

Galectin-3/Gelatin Electrospun Scaffolds Modulate Collagen Synthesis in Skin Healing but Do Not Improve Wound Closure Kinetics.

Chronic wounds remain trapped in a pro-inflammatory state, with strategies targeted at inducing re-epithelialization and the proliferative phase of healing desirable. As a member of the lectin family, galectin-3 is implicated in the regulation of macrophage phenotype and epithelial migration. We investigated if local delivery of galectin-3 enhanced skin healing in a full-thickness excisional C57BL/6 mouse model. An electrospun gelatin scaffold loaded with galectin-3 was developed and compared to topical delivery of galectin-3. Electrospun gelatin/galectin-3 scaffolds had an average fiber diameter of 200 nm, with 83% scaffold porosity approximately and an average pore diameter of 1.15 μm. The developed scaffolds supported dermal fibroblast adhesion, matrix deposition, and proliferation in vitro. In vivo treatment of 6 mm full-thickness excisional wounds with gelatin/galectin-3 scaffolds did not influence wound closure, re-epithelialization, or macrophage phenotypes, but increased collagen synthesis. In comparison, topical delivery of galectin-3 [6.7 µg/mL] significantly increased arginase-I cell density at day 7 versus untreated and gelatin/galectin-3 scaffolds (p < 0.05). A preliminary assessment of increasing the concentration of topical galectin-3 demonstrated that at day 7, galectin-3 [12.5 µg/mL] significantly increased both epithelial migration and collagen content in a concentration-dependent manner. In conclusion, local delivery of galectin 3 shows potential efficacy in modulating skin healing in a concentration-dependent manner.