wound healing

Radiation dermatitis is the most common side-effect of radiation therapy. The current daily therapy uses topical corticosteroids to reduce inflammation. However, long-term usage may cause some side-effects. Aloe vera could act as an anti-inflammatory and antioxidant agent, and ozone exhibits an antioxidant dan bactericidal effect. The present study aimed to analyze the effect of topical administration of ozonated Aloe vera oil on inflammatory and growth factors in radiation dermatitis wounds. This was an experimental study with a "post-test only control group” design. A total number of 36 Sprague Dawley rats were divided into two control and four intervention groups. C1: no intervention, C2: hydrocortisone ointment, P1: Aloe vera oil, P2/P3/P4: ozonated Aloe vera oil 300/600/1200 mg/ml. Termination and histopathological analysis of inflammatory and growth factors were performed after seven days of treatment. Statistical analysis was performed using SPSS version 22 (IBM corporation, USA). The normality test of the data was carried out using the Sapphiro Wilk test. Normally distributed data were subjected to the One-Way ANOVA test and continued with the Post Hoc LSD test after a significant difference was obtained. Data that were not normally distributed were tested using the Kruskal-Wallis test, followed by the Mann-Whitney U test. Therefore, all values obtained were considered significant at P < 0.05. Significant differences were found between the control and the treatment groups. Decreased tumor necrosis factor-alpha expression, neutrophil infiltration, endothelial damage, and increased tumor growth factor beta, platelet-derived growth factor, and fibroblast count were seen after seven days of intervention. Ozonated Aloe vera oil can accelerate wound healing of radiation dermatitis.

Traditional wound dressings primarily promote passive wound healing and infrequently promote active wound healing by influencing skin cell. It is known that electrical stimulation (ES) can control the actions of skin cells. In the present study, the conductive electrospun PU/rGO was designed and fabricated and its qualities as skin wound dressings in animal models were examined. 

In this study, nanocomposite PU (polyurethane)/rGO (reduce graphene oxide) was synthesized using an electrospinning process, investigated via scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), water contact angle, degradation studies, electrochemical impedance spectroscopy (EIS), bactericidal efficacy, hemolysis and MTT assay.  Then, the scaffolds were grafted in full-thickness wounds of animal rats and evaluated by wound closure and histological.

The results showed that the PU/rGO scaffold exhibited antibacterial activity in comparison with PU scaffold and viability showed a notable improvement in cell promotion. In the histopathological analysis, improved dermis development and collagen deposition at the healed wound area of the PU/rGO scaffold with electrical stimulation in comparison to other groups were observed. 

A PU/rGO scaffold with electrical stimulation could be an appropriate option for skin tissue engineering and wound healing.

Context: 

Recent advances in induced pluripotent stem cells (iPSCs), CRISPR-Cas9 gene editing, nanotechnologies, and artificial intelligence have revolutionized regenerative medicine (RM) as a transformative field for tackling difficult medical problems. These breakthroughs promise specific treatments, proper restoration of tissue function, and substantial improvements in the quality of life for patients whose ailments cannot yet be cured.This review explores cutting-edge advancements in RM platforms such as stem cell therapy, gene editing, 3D bioprinting, and nanotechnology. The study also aims to shed light on the challenges of clinical translation and policy implications, which are crucial for fostering sustainable and progressive advances in the discipline. 

Evidence Acquisition: 

This manuscript draws on cutting-edge research on the development and application of RM technologies. It synthesizes data on stem cells, gene therapy, tissue engineering, the in vitro organoid industry, artificial intelligence (AI), and nanotechnology that illustrate therapeutic potential. It also aims to identify ethical, regulatory, and practical hurdles for translating RM from research to clinical practice.

Breakthroughs such as those in iPSC-derived organoids, CRISPR-Cas9 gene editing, 3D bioprinting, and nanostructured materials exhibit significant promise in preclinical and clinical settings. Platforms such as organ-on-chip and AI tools further enhance drug discovery and treatment monitoring, while biomaterials and scaffold-based approaches enhance tissue repair and regeneration. Nevertheless, despite these advances, challenges persist regarding scale-up, safety, and ethical considerations.

Innovations in RM represent a paradigm shift from purely symptomatic treatments to restorative therapies. Successful integration of RM into clinical practice will require multidisciplinary collaborative work, imposition of rigorous safety protocols, and enabling regulatory frameworks. Addressing these challenges would enable RM to realize its true potential as a foundation for 21st-century healthcare.

Chronic wounds, a major clinical challenge, still need to develop new methods based on efficient technologies to improvetreatment results. Stem cells, particularly mesenchymal stem cells (MSC), as an advanced approach in skin regenerativemedicine, brought new hopes. The multifaceted effects of MSCs, including paracrine signaling, trophic factor secretion, andmodulation of the wound microenvironment, orchestrate a cascade of regenerative, plays a critical role in tissue repair. Preclinicalinvestigations have revealed the regenerative capacity of MSCs in accelerating wound closure, promoting angiogenesis, andfostering a pro-healing environment in chronic wound models. Clinical trials have also confirmed these findings and show theefficacy of MSC treatment in accelerating wound healing and improving the quality of healed tissue in patients with chronicwounds. Despite the therapeutic progress, key issues, such as optimal cell sourcing, cell dosage, delivery modalities, andlong-term safety profiles, there are a number of unresolved issues which need to be dealt with. This review aims to provide acomprehensive overview of current state of stem cell research in wound healing, and offers a new new hope for effective andinnovative treatments in regenerative medicine.

Chemical drugs are effective for wound healing, but herbal drugs with relative safety mainly reduce the adverse effects of chemical drugs in wound healing. The use of Opuntia ficus-indica oil and punica granatum oil as a natural remedy is prevalent due to the perceived beneficial properties. The aim of the present study is to compare the impact of “opuntia oil” and “punica oil” separately and in combination on skin wound healing.

This triple-blind clinical trial included 32 male adult New Zealand rabbits with a mean weight ranging from 1.5 to 2.0 Kg. Four circular standardized wounds were created on the dorsal region of each rabbit using a sterile biopsy punch with a diameter of 8 mm. The wounds intentionally left uncovered and the wound on the upper right side was not treated. The wound located on the upper left side was subjected to treatment with Opuntia ficus-indica oil. Punica granatum oil was used to treat a wound located on the lower right side. The lower-left-side wound was ultimately treated with a mixture of opuntia ficus-indica oil and punica granatum oil. The three experimental groups received daily treatment including topical application of 10 µl of opuntia ficus-indica oil, punica granatum oil, or a combination of these two oils, and wound healing in the groups was compared on days 1, 3, 7, and 14.

Wound healing in experimental groups showed a significant difference compared to the control group. The combination group exhibited the greatest mean value of wound contraction at day 14, reaching 84.6% at the experimental site. The analysis of inflammatory cell count revealed that the experimental groups treated with punica granatum oil exhibited the greatest mean values, reaching 68% on day one. Additionally, the mean values of epithelial thickness rose with time in all groups, with the combination group displaying a mean value of 38.5±3.5 um on day 14. There were notable differences between the control and experimental groups throughout all healing phases.

The results of the study showed that both opuntia ficus-indica oil and punica granatum oil are effective in wound healing compared to the control groups.

The aim of the present study was to investigate the potential of Nanochelating-based copper to accelerate the wound healing process and prevent infection in burn wounds.

Six to eight-week- old female BALB/c mice were burned with a 1 cm2 heated copper plate on the left flank and then divided into four treatment groups, treated with C8 (nanochelating-based CuNPs), cold cream (supplementary materials) as a control drug, Silver Sulfadiazine and no treatment, respectively. Skin tissue samples were taken from the mice on days 0, 3, 8, 15 and 24. One piece was fixed in 10% neutral buffered formalin for pathological examination and the others were stored at -80°C until used for pro-inflammatory and growth factor gene expression.

The healing process in the group treated with 10 mg/ml C8 was significantly faster, and the survival rate of the mice in this group was significantly higher than in the other groups. The pro-inflammatory genes were expressed and down-regulated earlier in the C8 treated mice. Histopathology confirmed the higher cure rate in the group treated with 10 mg/ml C8 compared to other control groups.

C8 has beneficial effects on the healing of burn wounds and the effective dose of this compound should be further investigated. The present study demonstrates the anti-inflammatory properties of nano-chelate-based copper particles' on mouse skin burns. This research opens up new possibilities in dermatology and burn therapy and highlights the potential of copper-based formulations in the treatment of burn injuries.

Due to the critical importance of post-surgical care for pilonidal sinus wounds, particularly in managing edema, infection, and related complications, it is essential to promote rapid wound healing.

This study aimed to evaluate the effect of Teucrium polium extract ointment as a wound repair agent for open pilonidal sinus surgery.

This randomized double-blind clinical trial was conducted from April 2021 to March 2022. A total of 132 participants admitted to public hospitals in Yasuj with pilonidal sinus disease were randomized into three groups: T. polium ointment, serum, and placebo. The primary outcomes were changes in wound size and wound recovery time after surgery, while secondary outcomes included changes in wound edema and wound exudate.

The results indicated that the mean changes in wound size were statistically significant across all three groups over time (P <0.001). Between-group comparisons showed that from weeks 4 to 8, differences between the three groups were statistically significant (P< 0.001). Wound recovery time demonstrated a significant difference between the ointment and serum groups (P = 0.006) and between the ointment and placebo groups (P < 0.001). Wound edema and exudate improved over time for all three groups (P < 0.001), but follow-up results revealed a significant difference among the groups (P < 0.001).

Based on the findings of this study and the comparison of the effects of T. polium ointment, it can be concluded that this ointment positively impacts wound healing following pilonidal sinus surgery, enhancing the healing process in both short-term and longterm care.

Natural component-included scaffolds can provide numerous benefits for skin healing and tissue regeneration. Nanofibers (NFs) with intricately intertwined three-dimensional structures afford an exclusive matrix for delivering therapeutics. This research assessed nanofibrous scaffolds loaded with Achillea wilhelmsii extract (5-15 wt%) for skin tissue engineering. 

A. wilhelmsii-loaded scaffolds, composed of poly(vinyl alcohol) (PVA) and chitosan (CS), were fabricated by the electrospinning process. Subsequently, the physicochemical properties of the scaffolds were evaluated through relevant analyses. The antioxidant activity and degradation rate of the scaffolds were also determined. Cell viability and scratch assays on dermal fibroblasts were conducted to assess proliferation and migration activities.  

Electron micrographs revealed interconnected fibers with a nano-scale diameter (> 400 nm) and uniform morphology. Additionally, the intact presence of A. wilhelmsii extract in the polymeric matrix was confirmed without any undesirable interactions. The proposed scaffolds verified favorable mechanical properties, a hydrophilic nature, high volume porosity (>90%), and water absorption capability (<500%). Besides, the findings demonstrated the remarkable radical scavenging ability of A. wilhelmsii extract in the nanofibrous scaffolds, along with controlled degradation kinetics over 72 h. The viability assay proved that the A. wilhelmsii-loaded scaffolds not only exhibited no cytotoxicity but also improved cell proliferation. The scaffolds also significantly accelerated fibroblast migration and complete closure of scratched areas. 

At last, the obtained results revealed that A. wilhelmsii-loaded PVA/CS NFs can be applied as a potential scaffold for skin regeneration and wound healing promotion.

This study assessed how Silver nanoparticles (Ag NPs) and hydroalcoholic extract of Salvia officinalis (Sage) influence the expression levels of the vascular endothelial growth factor (VEGF) and matrix metalloproteinase 2 (MMP2) genes, which play a role in wound healing.

An excision wound was induced on the back of the 48 adult male mice. Wound treatments done with AgNPs and Salvia officinalis extract in separate animal groups for 14 days. On two weeks after treatment, the wound skin tissue was removed and gene expression analysis was done by real-time polymerase chain reaction.

The results showed that the expression of both target genes (VEGF and MMP2) in the wound skins treated with 0.05% Ag NPs increased significantly compared with the wound skin of control. The expression of VEGF gene increased significantly in the wound tissues treated with Sage extract compared with the Vaseline group, but the expression of MMP2 gene didn’t change significantly. The expression of two target genes increased significantly in the wound tissues treated with 0.5% Sage extract plus 0.05% Ag NPs in comparison to the wound tissues treated with 0.5% Sage extract alone. The expression of the two target genes did not significantly differ in the wound tissues treated with Sage extract and Ag NPs compared to those treated with 0.05% Ag NPs alone.

Based on the results above, it can be concluded that the combination of hydroalcoholic extract of sage and low doses of Ag NPs exhibits significant healing activity and could serve as a viable option for wound healing management.

Post tooth extraction type of wound healing is a convoluted process that helps wounds reform. This study aims to evaluate the impact of polycaprolactone-hydroxyapatite zeolite nanocomposites on the healing processes of mucosa overlying post-extraction alveolus.

Fifteen healthy cats with premolar lower tooth involvement were selected for tooth extraction. The biopsy sampling from the mucosa of the alveolus was performed on the 10th postoperative day. The cats were grouped as control, plateletrich plasma (PRP), and nano polycaprolactone-hydroxyapatite zeolite.

The histopathologic analysis showed that contrary to controls and PRP, the nano group had a lower presence of inflammatory cells, a complete irregular thick epithelium, more granulation tissue, and more fibrosis. So, nano polycaprolactonehydroxyapatite zeolite accelerated the healing process after tooth extraction.

Nanocomposite containing nano zeolite can improve wound healing after tooth extraction.

Cold atmospheric plasma (CAP) has emerged as a promising therapy for wound healing to deliver controlled doses of reactive species to tissues. Argon and helium, as gases used in CAP, are noted for their unique properties and therapeutic potential.

This study compared the effects of argon and helium atmospheric cold plasma jets on wound healing in a rat model, assessing histopathological changes and biochemical parameters.

This randomized, controlled experimental study involved 18 male Wistar rats randomly assigned to control, helium-treated, and argon-treated groups. Wounds were created between the shoulders under anesthesia, treated with respective plasmas, and monitored for healing progress through macroscopic and microscopic evaluations.

Hemoglobin (HGB) and hematocrit (HCT) levels were significantly higher in experimental groups compared to controls (P < 0.05), while mean corpuscular volume (MCV) was lower (P < 0.05). Tumor necrosis factor alpha (TNF-α) levels were highest in helium-treated and lowest in argon-treated rats (P < 0.05). Argon-treated rats showed enhanced IL-6, hyperemia, angiogenesis, and re-epithelialization, with lower TNF-α and necrotic layer thickness than other groups (P < 0.05).

Both argon and helium atmospheric cold plasma jets enhanced wound healing in rat models, demonstrating superior efficacy in promoting angiogenesis and re-epithelialization processes.

Exosomes stimulate tissue regeneration and can be a substitute customary therapies of wound healing. The study aimed to compare the wound healing effects of exosome derived from Mesenchymal Stem Cells (MSCs) and other cells in wounds.

We searched PubMed, MEDLINE, EMBASE, International Clinical Trials Registry Platform, Clinical Trials, Cochrane Library, Wiley, Google Scholar, ISI Web of Knowledge, and Scopus study design, study location, various types of cell origin, and the healing outcome of extracted exosome. Two reviewer authors independently investigated and assessed the titles and abstracts of all articles; the third reviewer determined disagreement between them. Data were documented about study design, study location, various types of cell origin, and the healing outcome of extracted exosome.

A total of 2896 records were choice in an initial search for studies that used exosome for wound healing. Ultimately, 13 studies (seven articles applied MSC as origin of exosome, six studies used other cells expect MSCs as origin of exosome for wound healing) were included in this study. These articles were published from 2001 to December, 2023. This review study showed that MSC-derived exosomes have more wound-healing effects in angiogenesis, proliferation, collagen synthesis, and re-epithelialization. On the other hand, exosome with different cell origin has more wound-healing effects, such as proliferation, re-epithelialization, angiogenesis, and collagen synthesis.

Both MSC-derived exosomes and exosome with different cell origin, have great effects on the wound healing process. But, MSC-derived exosomes have better effects on the wounds that need to more angiogenesis and cell proliferation. Also, exosomes with different cell origin can have better effects on the wounds with more requirement of cell proliferation, and re-epithelialization.

Traditional medicine recommends herbal medicines for metabolic disorders. The present study explores the skin wound healing potential of Hypericum helianthemoides (H. helianthemoides) extract in diabetic and non-diabetic rats.

Following wound induction in diabetic (n=50) (induced by a single dose of streptozotocin) and non-diabetic (n=50) rats, H. helianthemoides extract (5% and 10%) was administered versus standard drug phenytoin (1%) and Osrin to positive and sham control groups. Tropical ointment therapy was applied once a day until the end of the study period (20 days). A Vernier caliper (with a 0.1 mm accuracy) was used to measure the wound length at 1, 3, 7, 11, 15, and 20 days after induction. Furthermore, pathological examination categorized the wound healing process into five categories: poor, mild, moderate, fair, and excellent.

On the study’s first day, both diabetic and nondiabetic rats had the same wound area size. After 11 days, the wound area size significantly decreased in groups treated with 5% and 10% H. helianthemoides extract compared to the sham and control groups (P<0.001). Hence, based on the wound pathological evaluation scale, the most frequent phenytoin and H. helianthemoides extract-treated groups were classified as moderate to excellent (P<0.05).

H. helianthemoides extract accelerates full-thickness wound healing in diabetic and non-diabetic rats

 Diabetic Foot Ulcer (DFU) might be worsened by neuropathy and vascular issues. This condition can cause 14.3% fatality, stressing the need for effective wound healing therapy. Wound healing is a complex biological process, and human Wharton's Jelly Mesenchymal Stem Cells (hWJMSCs) may help manage DFU treatment issues. This research focuses on utilizing a gel carrier to deliver bioactive substances from Wharton's Jelly Mesenchymal Stem Cells secretome (hWJ-MSCs-Sec) as a possible treatment for DFU.

 To maintain quality, hWJMSCs-Sec is thoroughly mixed with carbomer gel and freeze-dried. ELISA test is performed to determine the characterization of the gel of hWJMSCs-Sec such as Keratinocyte Growth Factor (KGF), Platelet-Derived Growth Factor (PDGF), Hepatocyte Growth Factor (HGF), Epidermal Growth Factor (EGF), and Heparin-Binding EGF-Like Growth Factor (HB-EGF). The antioxidant activity was also measured with Hydrogen peroxide (H2O2), Nitric oxide (NO), and Ferric Reducing Antioxidant Power (FRAP) assay. Proliferation assay was utilized using WST-8 and the wound healing potential was assessed via the migration cell ability of scratched-human skin fibroblast (BJ cells).

 The freeze-dried hWJ-MSCs-Sec showed higher levels of KGF, HGF, PDGF, EGF, HB-EGF, and the antioxidant activities compared to fresh hWJ-MSCs-Sec. Additionally, the gel of freeze-dried hWJ-MSCs-Sec exhibited higher levels compared to the gel of fresh hWJMSCs-Sec. This was evidenced by faster closure of scratched wounds on BJ cells treated with hWJMSCs-Sec and freeze-dried hWJ-MSCs-Sec gel.

 The freeze-dried hWJ-MSCs-Sec gel exhibits superior quality compared to the non-freeze-dried hWJ-MSCs-Sec gel. This demonstrates that the freeze-drying procedure can maintain the bioactive chemicals found in hWJMSCs-Sec, potentially enhancing the efficacy of this gel in promoting cell regeneration for wound healing.

Burn injury is still the leading cause of mortality and morbidity in burn patients.  We comapred healing effect of Hypericum perforatum, silver sulfadiazine and alpha ointments on burn injuries in rat model.

Sixty female Sprague-Dawley rats in an animal experimental study were randomly divided to 5 equal groups as H. perforatum, silver sulfadiazine and (SSD), alpha, gel base and the burn injury left untreated. Wounds were assessed macroscopically and histologic after burn injury and on days 7th, 14th and 21st after treatments.

Burn wounds decreased in size on day 7th in H. perforatum group (P<0.01). Regarding scoring the inflammation, re-epithelialization, angiogenesis, formation of granulation tissue and number of macrophage, the best scores were visible in H. perforatum group, and the worst in the gel base and the burn injury left untreated (P<0.01).

H. perforatum was shown to significantly induce re-epithelialization, angiogenesis and granulation tissue and decrease the inflammation resulting into a healing process in burn wounds. As H. perforatum is inexpensive and an easily available herbal medicine, it can be considered as a therapeutic of choice to ameliorate burn injuries.