Stages Of Wound Healing Research Articles

Development of a multifunctional nano-hydroxyapatite platform (nHEA) for advanced treatment of severely infected full-thickness skin wounds

The treatment of full-thickness skin injuries complicated by severe infection is hampered by the lack of comprehensive solutions that can regulate the various stages of wound healing. Consequently, there is an urgent need for a multifunctional dressing capable of multi-level regulation. In this study, we propose a novel solution by covalently integrating ε-poly-l-lysine-grafted gallic acid (EG) and in situ bioreduced silver nanoparticles (AgNPs) onto nano-hydroxyapatite (nHAP), thereby developing a multi-layered, multifunctional nanoplatform (nHEA). Cell experiments have shown that, compared to nHAP and nHAP loaded only with EG (nHEG), the addition of AgNPs to nHEA confers excellent antibacterial properties while maintaining optimal biocompatibility. The incorporation of EG onto nHEG and nHEA imparts antioxidation, anti-inflammatory, and pro-angiogenic functions, and the release of Ca2+ and EG further enhances fibroblast migration and collagen secretion. In a rat model of full-thickness skin injury with severe infection, nHEA demonstrates remarkable antibacterial and anti-inflammatory effects, along with promoting collagen remodeling and regeneration. Together, both cell experiments and animal studies confirm the significant potential of this innovative multifunctional nanoplatform in the treatment of full-thickness skin injuries with severe infection. Statement of significanceTreating infected full-thickness skin injuries poses a longstanding challenge due to the lack of comprehensive solutions that can regulate different stages of wound healing. This study introduces a novel multifunctional nanoplatform, nHEA, developed by covalently integrating ε-poly-l-lysine grafted with gallic acid (EG) and in situ bioreduced AgNPs onto nano-hydroxyapatite (nHAP). Cell experiments reveal that the integration of AgNPs enhances nHEA's antibacterial performance while maintaining optimal biocompatibility. The inclusion of EG bestows antioxidant, inflammation-regulating, and angiogenetic properties upon nHEA, and the release of Ca2+ and EG stimulates the migration and collagen secretion of fibroblast cells. Consequently, nHEA exhibits superior antibacterial and inflammation-regulating efficacy, and stimulates collagen remodeling and regeneration in vivo, making it a promising treatment for severely infected skin injuries.

Synergistic Drug-Loaded Shear-Thinning Star Polymer Hydrogel Facilitates Gastrointestinal Lesion Resection and Promotes Wound Healing.

Easy injection, long-lasting barrier, and drug loading are the critical properties of submucosal injection materials for endoscopic surgery. However, conventional injectable polymers face challenges in simultaneously attaining these properties due to the inherent conflict between injectability and in situ stability. Here, a multi-arm star polymer hydrogel (denoted as βCP hydrogel) with long-lasting submucosal barrier (exceeding 120 min), rapid hemostasis, and sustained antibacterial properties is successfully developed by grafting poly(oligo(ethylene glycol) methyl ether methacrylate)(PEGMA) side-chains from β-CD via atom transfer radical polymerization (ATRP). During the onset of shearing, βCP hydrogel experiences the unwinding of polymer side-chains between neighboring star polymers, which facilitates the process of endoscopic injectability. After submucosal injection, βCP hydrogel undergoes the winding of polymer side-chains, thereby establishing a long-lasting barrier cushion. Meanwhile, owing to its distinctive structures with a hydrophobic inner cavity and an outer layer of hydrophilic polymer side-chains, βCP hydrogel enables simultaneous loading and on-demand release of diverse categories ofdrugs. This unique performance can adapt to the diverse demands during different stages of wound healing in a porcine endoscopic surgery model. These results indicate an appealing prospect for new application of star polymers as a good submucosal injection material in endoscopic treatments.

A new mechanism in negative pressure wound therapy: interleukin-17 alters chromatin accessibility profiling.

Negative pressure wound therapy (NPWT) is extensively used in clinical settings to enhance the healing of wounds. Despite its widespread use, the molecular mechanisms driving the efficacy of NPWT have not been fully elucidated. In this study, skin wound-healing models were established, with administration of NPWT. Vimentin, collagen I, and MMP9 of skin tissues were detected by immunofluorescence (IF). Gene expression analysis of skin wound tissues was performed by RNA-sequencing (RNA-seq). Protein expression was assayed by a Western blotting or IF assay, and mRNA levels were quantified by quantitative PCR. Chromatin accessibility profiles of fibroblasts following NPWT or IL-17 exposure were analyzed by ATAC-seq. In rat wound-healing models, NPWT promoted wound repair by promoting reepithelialization, extracellular matrix (ECM) synthesis, and proliferation, which mainly occurred in the early stage of wound healing. These differentially expressed genes (DEGs) in NPWT wounds versus control wounds were enriched in the IL-17 signaling pathway. IL-17 was identified as an upregulated factor following NPWT in skin wounds. Moreover, the IL-17 inhibitor secukinumab (SEC) could abolish the promoting effect of NPWT on wound healing. Importantly, chromatin accessibility profiles were altered following NPWT and IL-17 stimulation in skin fibroblasts. Our findings suggest that NPWT upregulates IL-17 to promote wound healing by altering chromatin accessibility, which is a novel mechanism for NPWT's efficacy in wound healing.NEW & NOTEWORTHY To our knowledge, this is the first report of the efficacy of negative pressure wound therapy (NPWT) in promoting wound healing via IL-17. Moreover, NPWT and IL-17 can alter chromatin accessibility. Our study identifies a novel mechanism for NPWT's efficacy in wound healing.

The Role of TNF-Alpha in the Wound Healing Process: Molecular and Clinical Perspectives - A Systematic Literature Review

Wounds are conditions of damage and partial loss of body tissue caused by physical trauma, sharp objects, blunt objects, temperature fluctuations, chemical exposure. Wound healing is a complex interaction between cells, cytokines, mediators, and blood vessels as a natural physiological response to tissue damage. TNF-α has a crucial role in the wound healing process, facilitating body immunity, immune cell mobilization, fibroblast cell proliferation, keratinocytes, and growth factor expression. Although TNF-alpha has benefits in the early stages of wound healing, excessively high levels or a sustained inflammatory response can lead to problems, such as excessive scar tissue formation or blockages, which can impede the wound healing process. This study utilized the PRISMA-ScR (Scoping Review) protocol. A review was conducted of articles discussing the Role of TNF-Alpha in the Wound Healing Process: Molecular and Clinical Perspectives within the last 10 years. Literature search in this study using PubMed, ScienceDirect, Elsivier and Google Scolar databases Search using English, abstract and full text. After searching with the keywords: The Role of TNF-Alpha, 19,022 articles were found. The search continued using the keyword The Role of TNF-Alpha in the Wound Healing found 346 articles. The last search using the keyword The Role of TNF-Alpha in the Wound Healing: Molecular and Clinical found 26 articles. TNF-α plays an important role in the early stages of cutaneous wound healing, significantly delayed after day 3, but not by day 7. TNF-α has a crucial role in the early stages of skin wound healing, and its administration is recognized to have a positive impact on the healing response, which may pave the way for innovative strategies to address chronic skin wound healing problems.

Building erudition in the wound healing process: an inflammation model analysis

The main four stages of wound healing are hemostasis, inflammation, proliferation, and remodelling. In the inflammation stage, the body rids of pathogens and debris, and prepares for tissue regrowth. An ordinary differential equation model of the inflammation is constructed that expands on previous models and incorporates dynamics reported in the updated literature. The interaction between debris and apoptotic neutrophils, along with classical and alternative macrophages are included. In all, the model incorporates pathogens, debris, apoptotic neutrophils, neutrophil, M1 macrophages, and M2 macrophages. Parameter values are analysed based on 1. experimental data and 2. reported ranges and expected peak times of white blood cells. Next, global sensitivity analyses which is able to test change in parameter values in tandem is conducted to interpret the overall influence each parameter has on white blood cell, debris, and pathogen output.

Porous Functionally Graded Scaffold prepared by a single-step freeze-drying process. A bioinspired approach for wound care

Nowadays, chronic wounds are the major cause of morbidity worldwide and the healthcare costs related to wound care are a billion-dollar issue; chronic wounds involve a non-healing process that makes necessary the application of advanced wound dressings to promote skin integrity recovery. Functionally Graded Scaffolds (FGSs) are currently driving interest as promising candidates in mimicking the skin tissue environment and, thus, in enhancing a faster and more effective wound healing process. Aim of the present work was to design and develop a porous FGS based on κ-carrageenan (κCG) for the management of chronic skin wounds; a freeze-drying process was optimized to obtain in a single-step a three-layered FGS characterized by a pore size gradient functional to mimic the structure of native skin tissue. In addition to κCG, arginine and whey protein isolate were used as multifunctional agents for FGS preparation; these substances can not only intervene in some stages of wound healing but are able to establish non-covalent interactions with κCG, which were responsible for the production of layers with different pore size, water content capability and mechanical properties. Cell migration, adhesion and proliferation within the FGS structure were evaluated in vitro on fibroblasts and FGS wound healing potential was also studied in vivo on a murine model.

Low-temperature plasma jet suppresses bacterial colonisation and affects wound healing through reactive species.

An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-β levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.

Electrospun Nanofibers Loaded with Marigold Extract Based on PVP/HPβCD and PCL/PVP Scaffolds for Wound Healing Applications.

Marigold flower is a traditionally used plant material topically applied on the skin due to its anti-inflammatory properties and antibacterial activity. This potential of action justifies the implementation of marigold extract in nanofiber scaffolds based on poly-vinylpyrrolidone/hydroxypropyl-β-cyclodextrin (PVP/HPβCD) and polycaprolactone/polyvinylpyrrolidone (PCL/PVP) obtained by electrospinning for wound treatment. Using SEM, the morphology of electrospun scaffolds showed a fiber diameter in the range of 298-527 nm, with a uniform and bead-free appearance. ATR-FTIR spectroscopy confirmed the presence of marigold extracts in nanofibrous scaffolds. The composition of the nanofibers can control the release; in the case of PVP/HPβCD, immediate release of 80% of chlorogenic acid (an analytical and functional marker for marigold extract) was achieved within 30 min, while in the case of PCL/PVP, the controlled release was achieved within 24 h (70% of chlorogenic acid). All systems showed weak antibacterial activity against skin and wound-infecting bacteria Staphylococcus aureus (MIC 100 mg/mL), and Pseudomonas aeruginosa (MIC 200 mg/mL) and yeasts Candida albicans (MIC 100 mg/mL). Analysis of the effect of different scaffold compositions of the obtained electrofibers showed that those based on PCL/PVP had better wound healing potential. The scratch was closed after 36 h, compared to the 48 h required for PVP/HPβCD. Overall, the study shows that scaffolds of PCL/PVP nanofibers loaded with classic marigold extract have the best potential as wound dressing materials because of their ability to selectively modulate inflammation (via inhibition of hyaluronidase enzyme) and supportive antimicrobial properties, thereby aiding in the early stages of wound healing and repair.

Modulating macrophage phenotype for accelerated wound healing with chlorogenic acid-loaded nanocomposite hydrogel

Wound healing involves distinct phases, including hemostasis, inflammation, proliferation, and remodeling, which is a complex and dynamic process. Conventional preparations often fail to meet multiple demands and provide prompt information about wound status. Here, a pH/ROS dual-responsive hydrogel (OHA-PP@Z-CA@EGF) was constructed based on oxidized hyaluronic acid (OHA), phenylboronic acid-grafted ε-polylysine (PP), chlorogenic acid (CA)-loaded ZIF-8 (Z-CA), and epidermal growth factor (EGF), which possesses intrinsic antibacterial, antioxidant, and angiogenic capacities. Due to the Schiff base and Phenylboronate ester bonds, the hydrogel exhibited excellent mechanical properties, strong adhesion, good biodegradability, high biocompatibility, stable rheological properties, and self-healing ability. Moreover, introducing Z-CA as an initiator and nanofiller led to the additional cross-linking of hydrogel through coordination bonds, which further improved the mechanical properties and antioxidant capabilities. Bleeding models of liver and tail amputations demonstrated rapid hemostatic properties of the hydrogel. Besides, the hydrogel regulated macrophage phenotypes via the NF-κB/JAK-STAT pathways, relieved oxidative stress, promoted cell migration and angiogenesis, and accelerated diabetic wound healing. The hydrogel also enabled real-time monitoring of the wound healing stages by colorimetric detection. This multifunctional hydrogel opens new avenues for the treatment and management of full-thickness diabetic wounds.

The effect of human recombinant epidermal growth factor on neovascularization and pedicle division time in a rat interpolation flap model.

In practice, waiting 2-3 weeks for interpolation flaps pedicle division result in certain morbidities and discomfort for patient. The division time of flap pedicle depends on neovascularization from the recipient bed and includes wound healing stages. We aimed to investigate the effect of recombinant human epidermal growth factor (rhEGF) on the flap viability during early pedicle division. Thirty-six rats were allocated to two main groups as control and study. A cranial based flap measuring 5 × 5 cm was elevated from the back, including all layers of the skin. While the cranial half of the defect was primarily closed, the flap was inset into the distal half. In the study group, a single dose of 20 μg EGF was injected into the recipient site and wound edges before the flap inset. The control group received no treatment. Each main group was divided into three subgroups based on pedicle division time of 8, 11 and 14 days. After pedicle division, each flap was monitored and photographed for 7 days, and histopathological samples were collected. Viable and necrotic areas were compared, and flaps were examined histopathologically. The necrosis area in the study group on the 11th day was significantly lower than that in the control group. The fibroblastic activity, granulation tissue and neovascularization on the 8th day, the granulation tissue level on the 11th day, and the neovascularization level on the 14th day were significantly higher in the study groups. Following the application of EGF, the necrosis area decreased within the study group. Histopathological assessments revealed a statistically significant increase in parameters related to granulation tissue and fibroblastic activity, notably neovascularization, across all subgroups within the study. It was concluded that the use of EGF positively affected the neovascularization, and flaps could be divided earlier.

Ethanolic extract of Gracilaria spp. Attenuates the inflammatory stage of oral mucosa wound healing: An in vivo study.

Millions of bacteria present in the mouth cavity contribute to the challenging management of oral mucosa injury. On the other hand, Gracilaria spp. (red algae) is one of the widely cultivated algae that have a strong potential as a wound-healing agent for oral mucosa injury. This study aimed to investigate the wound-healing property of the red algae by observing its effect on polymorphonuclear (PMN), a neutrophil that is usually recruited during the initial wound healing. The extract was obtained through maceration and used as bioactive ingredient in gel preparation. Rattus norvegicus with incision wounds in the oral mucosa was used as the animal model. Our results revealed that rats treated with the red algae gel had significantly lower PMN on the injury site (P < 0.01) as observed on days 1, 3, and 5. Identification using gas chromatography-mass spectrometry showed that the extract was rich in hexadecenoic acid and glycerol. The brine shrimp lethality test suggested low cytotoxicity of this extract with LC50 = 10694.93 mg/mL. In conclusion, the extract could be potentially used as bioactive ingredient in gel formulation for topical management of oral mucosa wounds. Further, research to confirm these findings is warranted.

Enhancing cutaneous wound healing: A study on the beneficial effects of nano-gelatin scaffold in rat models.

The challenges in achieving optimal outcomes for wound healing have persisted for decades, prompting ongoing exploration of interventions and management strategies. This study focuses on assessing the potential benefits of implementing a nano-gelatin scaffold for wound healing. Using a rat skin defect model, full-thickness incisional wounds were created on each side of the thoracic-lumbar regions after anesthesia. The wounds were left un-sutured, with one side covered by a gelatin nano-fibrous membrane and the other left uncovered. Wound size changes were measured on days 1, 4, 7, and 14, and on day 14, rats were sacrificed for tissue sample excision, examined with hematoxylin and eosin, and Masson's trichrome stain. Statistical comparisons were performed. The gelatin nanofibers exhibited a smooth surface with a fiber diameter of 260 ± 40 nm and porous structures with proper interconnectivity. Throughout the 14-day experimental period, significant differences in the percentage of wound closure were observed between the groups. Histological scores were higher in the experiment group, indicating less inflammation but dense and well-aligned collagen fiber formation. A preliminary clinical trial on diabetic ulcers also demonstrated promising results. This study highlights the potential of the nano-collagen fibrous membrane to reduce inflammatory infiltration and enhance fibroblast differentiation into myofibroblasts during the early stages of cutaneous wound healing. The nano-fibrous collagen membrane emerges as a promising candidate for promoting wound healing, with considerable potential for future therapeutic applications.

Identification of IGF2 promotes skin wound healing by co-expression analysis.

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

A Preliminary Study on Quantitative Analysis of Collagen and Apoptosis Related Protein on 1064 nm Laser-Induced Skin Injury.

To investigate the associated factors concerning collagen and the expression of apoptosis-related proteins in porcine skin injuries induced by laser exposure, live pig skin was irradiated at multiple spots one time, using a grid-array method with a 1064 nm laser at different power outputs. The healing process of the laser-treated areas, alterations in collagen structure, and changes in apoptosis were continuously observed and analyzed from 6 h to 28 days post-irradiation. On the 28th day following exposure, wound contraction and recovery were notably sluggish in the medium-high dose group, displaying more premature and delicate type III collagen within the newly regenerated tissues. The collagen density in these groups was roughly 37-58% of that in the normal group. Between days 14 and 28 after irradiation, there was a substantial rise in apoptotic cell count in the forming epidermis and granulation tissue of the medium-high dose group, in contrast to the normal group. Notably, the expression of proapoptotic proteins Bax, caspase-3, and caspase-9 surged significantly 14 days after irradiation in the medium-high dose group and persisted at elevated levels on the 28th day. During the later stage of wound healing, augmented apoptotic cell population and insufficient collagen generation in the newly generated skin tissue of the medium-high dose group were closely associated with delayed wound recovery.

A review of the current state of natural biomaterials in wound healing applications.

Skin, the largest biological organ, consists of three main parts: the epidermis, dermis, and subcutaneous tissue. Wounds are abnormal wounds in various forms, such as lacerations, burns, chronic wounds, diabetic wounds, acute wounds, and fractures. The wound healing process is dynamic, complex, and lengthy in four stages involving cells, macrophages, and growth factors. Wound dressing refers to a substance that covers the surface of a wound to prevent infection and secondary damage. Biomaterials applied in wound management have advanced significantly. Natural biomaterials are increasingly used due to their advantages including biomimicry of ECM, convenient accessibility, and involvement in native wound healing. However, there are still limitations such as low mechanical properties and expensive extraction methods. Therefore, their combination with synthetic biomaterials and/or adding bioactive agents has become an option for researchers in this field. In the present study, the stages of natural wound healing and the effect of biomaterials on its direction, type, and level will be investigated. Then, different types of polysaccharides and proteins were selected as desirable natural biomaterials, polymers as synthetic biomaterials with variable and suitable properties, and bioactive agents as effective additives. In the following, the structure of selected biomaterials, their extraction and production methods, their participation in wound healing, and quality control techniques of biomaterials-based wound dressings will be discussed.

Botulinum toxin type A inhibits M1 macrophage polarization by deactivation of JAK2/STAT1 and IκB/NFκB pathway and contributes to scar alleviation in aseptic skin wound healing

The non-neuronal and non-muscular effects of botulinum toxin type A (BTXA) on scar reduction has been discovered. This study was designed to investigate the effects of BTXA on macrophages polarization during the early stage of skin repair. A skin defect model was established on the dorsal skin of SD rats. BTXA was intracutaneous injected into the edge of wound immediately as the model was established. Histological examinations were performed on scar samples. Raw 264.7 was selected as the cell model of recruited circulating macrophages, and was induced for M1 polarization by LPS. Identify the signaling pathways that primarily regulated M1 polarization and respond to BTXA treatment. Application of BTXA at early stage of injury significantly reduced the scar diameter without delaying wound closure. BTXA treatment improved fiber proliferation and arrangement, and inhibited angiogenesis in scar granular tissue. The number of M1 macrophages and the levels of pro-inflammation were decreased after treated with BTXA in scar tissues. LPS activated JAK2/STAT1 and IκB/NFκB pathways were downregulated by BTXA, as well as LPS induced M1 polarization. At early stage of skin wound healing, injection of BTXA effectively reduced the number of M1 macrophages and the levels of pro-inflammatory mediators which contributes to scar alleviation. BTXA resisted the M1 polarization of macrophages induced by LPS via deactivating the JAK2/STAT1 and IκB/NFκB pathways.

A dual network cross-linked hydrogel with multifunctional Bletilla striata polysaccharide/gelatin/tea polyphenol for wound healing promotion

Wound healing is a dynamic and complex biological process, and traditional biological excipients cannot meet the needs of the wound healing process, and there is an urgent need for a biological dressing with multifunctionality and the ability to participate in all stages of wound healing. This study developed tea polyphenol (TP) incorporated multifunctional hydrogel based on oxidized Bletilla striata polysaccharide (OBSP) and adipic acid dihydrazide modified gelatin (Gel-ADH) with antimicrobial, antioxidant hemostatic, and anti-inflammatory properties to promote wound healing. The composite OBSP, Gel-ADH, TP (OBGTP) hydrogels prepared by double crosslinking between OBSP, TP and Gel-ADH via Schiff base bonding and hydrogen bonding had good rheological and swelling properties. The introduction of TP provided the composite hydrogel with excellent antioxidant antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coil). In the rat liver hemorrhage model and skin injury model, the OBGTP composite hydrogel had significant (p < 0.001) hemostatic ability, and had the ability to accelerate collagen deposition, reduce the expression of inflammatory factors, and promote rapid wound healing. In addition, OBGTP hydrogels had adhesive properties and good biocompatibility. In conclusion, OBGTP multifunctional composite hydrogels have great potential for wound healing applications.

Beyond Traditional Boundaries: A Review on Calotropis gigantea’s Efficacy in Wound Healing

Introduction: Wounds result from the disruption of cellular and anatomical continuity in living tissues due to external factors. Calotropis gigantea, also known as crown flower or giant milkweed (or "biduri" in Indonesia), is a small tree or shrub with white or purple flowers, widely used in traditional remedies. Its properties, including antimicrobial, cytotoxic, and wound-healing activities, have prompted this literature review to assess its efficacy in wound healing. Method: A thorough analysis of scientific findings and research conducted in the last 10 years, specifically after January 1, 2014, was undertaken. Data were collected from reputable databases, such as PubMed, Web of Science, and ScienceDirect. After applying publication limitations, three manuscripts were selected as the final outcomes of the review process. Result: The analysis of multiple studies reveals that C. gigantea possesses wound healing properties attributed to phytochemical constituents like flavonoids, tannins, alkaloids, and saponin. These constituents play vital roles in each stage of wound healing, including the inflammatory reaction, proliferation, and remodeling stages. Additionally, C. gigantea promotes wound healing, leaving minimal scar residues. Conclusion: Calotropis gigantea has demonstrated its ability to enhance wound healing through various mechanisms, including astringency, antibacterial activity, promotion of homeostasis, facilitation of collagen synthesis, enhancement of re-epithelialization, and stimulation of cell proliferation via its phytochemical constituents. However, due to the scarcity of recent studies, the plant's true efficacy in wound healing remains unclear.

Investigation of topical amniotic membrane suspension and ReGeneraTing Agent on early corneal stromal healing in rats

Innovative topical bioregenerative materials promoting corneal stromal healing provide valuable alternatives for treating patients with deep corneal ulcers, and particularly beneficial for those with a higher anaesthetic risk. This study aimed to investigate the effects of topical amniotic membrane suspension (AMS) and ReGeneraTing Agent (RGTA) on surgically induced deep stromal ulcers in rats. Eighteen Sprague-Dawley rats were divided into 3 treatment groups: control group (topical normal saline, TID); AMS group (topical AMS, TID); RGTA group (topical RGTA, Q2D). Corneal microsurgery was used to create deep stromal ulcer. Evaluations were performed by corneal opacity grading, spectral domain optical coherence tomography (SD-OCT), histopathology, and immunohistochemistry. One-way ANOVA and Dunnett's test were used for statistical analysis. By the seventh day of treatment, both the AMS and RGTA groups showed significantly greater thickness in corneal stroma (both p-value < 0.05) than the control group. Additionally, the RGTA group exhibited a significantly higher degree of myofibroblast infiltration in the stroma and a greater level of corneal opacity (p < 0.05). No significant differences in the count of inflammatory cells were noted. In conclusion, both AMS and RGTA have demonstrated effectiveness in promoting the early stages of stromal wound healing and wound defect recovery in our research. Both AMS and RGTA have good potential for treating deep corneal ulcers in small animals practice. Further research is necessary to investigate the long-term effects and mechanism of using topical AMS and RGTA on treating deep corneal ulcer in clinical practice.

Photobiomodulation preconditioned diabetic adipose derived stem cells with additional photobiomodulation: an additive approach for enhanced wound healing in diabetic rats with a delayed healing wound.

In this preclinical investigation, we examined the effects of combining preconditioned diabetic adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation (PBM) on a model of infected ischemic delayed healing wound (injury), (IIDHWM) in rats with type I diabetes (TIDM). During the stages of wound healing, we examined multiple elements such as stereology, macrophage polarization, and the mRNA expression levels of stromal cell-derived factor (SDF)-1α, vascular endothelial growth factor (VEGF), hypoxia-induced factor 1α (HIF-1α), and basic fibroblast growth factor (bFGF) to evaluate proliferation and inflammation. The rats were grouped into: (1) control group; (2) diabetic-stem cells were transversed into the injury site; (3) diabetic-stem cells were transversed into the injury site then the injury site exposed to PBM; (4) diabetic stem cells were preconditioned with PBM and implanted into the wound; (5) diabetic stem cells were preconditioned with PBM and transferred into the injury site, then the injury site exposed additional PBM. While on both days 4, and 8, there were advanced histological consequences in groups 2-5 than in group 1, we found better results in groups 3-5 than in group 2 (p < 0.05). M1 macrophages in groups 2-5 were lower than in group 1, while groups 3-5 were reduced than in group 2 (p < 0.01). M2 macrophages in groups 2-5 were greater than in group 1, and groups 3-5 were greater than in group 2. (p ≤ 0.001). Groups 2-5 revealed greater expression levels of bFGF, VEGF, SDF- 1α, and HIF- 1α genes than in group 1 (p < 0.001). Overall group 5 had the best results for histology (p < 0.05), and macrophage polarization (p < 0.001). AD-MSC, PBM, and AD-MSC + PBM treatments all enhanced the proliferative stage of injury repairing in the IIDHWM in TIDM rats. While AD-MSC + PBM was well than the single use of AD-MSC or PBM, the best results were achieved with PBM preconditioned AD-MSC, plus additional PBM of the injury.