Understanding wound healing in obesity

Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.

Mesenchymal stem cells in wound healing:A bibliometric analysis as a powerful research tool

Bibliographic analysis is still very rarely used in experimental basic study papers.The comprehensive bibliometric analysis of scientific literature on research progress and challenges in stem cell therapy for diabetic chronic wounds,which was conducted in the work of Shi et al can be a case study and a source of valuable information for writing reviews and experimental papers in this field.Basic experimental studies on a role of mesenchymal stem cells(MSCs)in wound healing that are published in 2023-2024,such as Zhang et al in 2023,Hu et al in 2023,Wang et al in 2023 are certainly also subjects for applying this powerful tool to analyze current research,challenges and perspectives in this field.This is due to the fact that these studies have addressed a great variety of aspects of the application of MSCs for the treatment of chronic wounds,such as using both the cells themselves and their various products:Sponges,hydrogels,exosomes,and genetic constructions.Such a wide variety of directions in the field of study and biomedical application of MSCs requires a deep understanding of the current state of research in this area,which can be provided by bibliometric analysis.Thus,the use of such elements of bibliographic analysis as publication count by year and analysis of top-10 keywords calculated independently or cited from bibliometric analysis studies can be safely recommended for every basic study manuscripts,primarily for the“Introduction”section,and review.

Preliminary pharmacological evaluation of Martynia annua Linn leaves for wound healing

Objective:To evaluate the wound healing potential of fractions from ethanol extract of Martynin annua(M.annua) Linn leaves.Methods:Ethanol extract of Af.annua Linn leaves was fractionate into three different fractions(MAF-A,MAF-B and MAF-C) which were screened for wound healing potential using two models:excision and incision on rats.The thin layer chromatography(TLC) profile of all fractions were analysed and TLC of luteolin was also done.The PovidoneIodine Ointment was used as reference for comparision.Excision and incision wounds were created on dorsal portion of rats for study.Wound contraction,biochemical parameters(protein level and hydroxyproline level) and histopathological study were performed in excision wound model whereas incision model was used for determination of tensile strength.Results:The wound contraction and tensile strength of skin tissues were observed significantly greater in MAF-C fraction treated group than other two fractions(P<0.01).In excision wound method(on day 18) protein content and hydroxyproline were found significantly higher in MAF-C group than control group(P<0.01).Histopathological study also showed better angiogenesis,matured collagen fibres and fibroblast cells as compared with the control group.Conclusions:In conclusion, our findings suggest that fiaction MAF-C from ethanol extract of M.annua leaves is found most effective in wound healing.

Effects of allogeneic PRP combined with ADSC on wound healing and serum HA and VEGF levels in mice

Objective:Elet-rich plasma(PRP)combined with adipose-derived mesenchymal stem cells(ADSC)on skin wound healing and serum hyaluronic acid(HA)and vascular endothelial growth factor(VEGF)levels in mice.Methods:Forty-five mice were randomly divided into three groups(n=15),which were control,ADSC,and ADSC+PRP.The wound injury model was established in all three groups.The control group was injected subcutaneously with normal saline,the ADSC group was injected subcutaneously with allogeneic PRP,and the ADSC+PRP was injected subcutaneously with ADSC and PRP.Wound healing was observed at 3 d,5 d,and 7 d after modeling,and histomorphological features were observed by HE staining.CollagenⅠand CollagenⅢlevels were detected using Western blot.The levels of serum HA and VEGF in each group were detected and compared.Results:The wound healing rate of ADSC group and ADSC+PRP group was significantly higher than that of control group at 3 d,5 d and 7 d after modeling(P<0.01).The wound healing rate of the ADSC+PRP group was significantly higher than that of the ADSC group(P<0.01).The inflammatory response of the control group and the ADSC group was significant at 3 and 5 d after modeling,and there was a small amount of granulation tissue in the ADSC group.The ADSC+PRP group had a milder inflammatory response and more granulation tissue;After 7 d,the ADSC+PRP group had more neovascularization and higher re-epithelialization rate.The control group and the ADSC group had poorer epithelialization and fewer new blood vessels.The expression levels of CollagenⅠand CollagenⅢin ADSC group and ADSC+PRP group were significantly higher than those in control group at 3 d,5 d and 7 d after modeling(P<0.01).CollagenⅠand CollagenⅢin the ADSC+PRP group were significantly higher than those in the ADSC group(P<0.01).Serum HA and VEGF in ADSC group and ADSC+PRP group were significantly higher than those in control group at 3 d,5 d and 7 d after modeling(P<0.01).Serum HA and VEGF were significantly higher in the ADSC+PRP group than in the ADSC group(P<0.01).Conclusion:Allogeneic PRP combined with ADSC can promote the regeneration and healing of skin wounds in mice.The mechanism may be related to the up-regulation of the expression of vascular endothelial growth factor and HA and the promotion of the formation of blood vessels and granulation tissue.

Effects of comprehensive nutrition support on immune function,wound healing,hospital stay,and mental health in gastrointestinal surgery

BACKGROUND Postoperative patients undergoing gastrointestinal surgery often encounter challenges such as low immune function,delayed wound healing owing to surgical trauma,and increased nutritional demands during recovery.AIM To assess the effect of comprehensive nutritional support program on immune function and wound healing in patients undergoing gastrointestinal surgery.METHODS This retrospective comparative study included 60 patients who underwent gastrointestinal surgery,randomly assigned to either the experimental group(n=30)or the control group(n=30).The experimental group received comprehensive nutritional support,including a combination of enteral and parenteral nutrition,whereas the control group received only conventional comprehensive nutritional support.Evaluation indicators included immune function markers(e.g.,white blood cell count,lymphocyte subsets),wound healing(wound infection rate,healing time),pain score[visual analog scale(VAS)score],and psychological status(anxiety score,depression score)7 days post-surgery)and duration of stay.RESULTS The immune function of patients in the experimental group was significantly better than that in the control group.The white blood cell count was 8.52±1.19×109/L in the experimental group vs 6.74±1.31×109/L(P<0.05).The proportion of CD4+T cells was higher in the experimental group(40.09%±4.91%)than that in the control group(33.01%±5.08%)(P<0.05);the proportion of CD8+T cells was lower(21.79%±3.38%vs 26.29%±3.09%;P<0.05).The CD4+/CD8+ratio was 1.91±0.32 in the experimental group whereas 1.13±0.23 in the control group(P<0.05).The wound infection rate of the experi-mental group was significantly lower than that of the control group(10%vs 30%,P<0.05),and the wound healing time was shorter(10.35±2.42 days vs 14.42±3.15 days,P<0.05).The VAS score of the experimental group was 3.05±1.04,and that of the control group was 5.11±1.09(P<0.05);the anxiety score(Hamilton Anxiety Rating Scale)was 8.88±1.87,and that of the control group was 12.1±3.27(P<0.05);the depression score(Hamilton Depression Rating Scale)was 7.37±1.41,and that of the control group was 11.79±2.77(P<0.05).In addition,the hospitalization time of the experimental group was significantly shorter than that of the control group(16.16±3.12 days vs 20.93±4.84 days,P<0.05).CONCLUSION A comprehensive nutritional support program significantly enhances immune function,promote wound healing,reduces pain,improves psychological status,and shortens hospitalization stays in patients recovering from gastrointestinal surgery.

Pharmacological studies on Buchanania lanzan Spreng.-A focus on wound healing with particular reference to anti-biofilm properties

Objective:To evaluate the wound healing activity of the methanolic root extract of Buchanania lanzan Spreng.(B.lanzan),with a focus on antimicrobial and anti-biofilm properties.Methods:The extract was evaluated for its wound healing properties(excision and incision models)as evident from the analysis of tensile strength and wound contraction.The extract was also screened for antibacterial properties against different Cram positive and Gram negative bacterial strains.B.lanzan was also studied for its effect on biofilm formation and disruption of preformed biofilms.The synergistic effect of B.lanzan was determined in combination with gentamicin.Results:Topical application of B.lanzan(10%w/w ointment)significantly increased(40.84%)the tensile strength in the incision wound model.B.lanzan also showed significant wound healing activity in excision model and such significant activity was observed from the 9th day.Whereas Soframycin displayed significant wound healing activity from the 6th day.It was found that root extracts of B.lanzan revealed significant inhibition against all tested pathogens.B.lanzan displayed antimicrobial activity against Cram positive(MIC 0.625 mg/mL)and Cram negative(MIC0.625-1.25 mg/mL).B.lanzan was able to reduce biofilm formation and also caused disruption of preformed biofilms in a manner similar to ciprofloxacin.However,gentamicin was found to be ineffective against biofilms formed by Gram negative organism.According to the fractional inhibitory concentration index,B.lanzan displayed synergistic activity when it was combined with gentamicin.Conclusions:From this study it may be concluded that the root extract of B.lanzan revealed significant wound healing potential,which was supported and well correlated with pronounced antibacterial activity of the tested plant parts.

Advances in flexible and wearable pH sensors for wound healing monitoring

Wound healing has been recognized as a complex and dynamic regeneration process and attracted increasing interests on its management.For effective wound healing management,a continuous monitoring on the wound healing based on sensors is essential.Since pH has been found to play an important role on wound healing process,a variety of pH sensors systems for wound healing monitoring have been greatly developed in recent years.Among these pH sensors,flexible and wearable pH sensors which can be incorporated with wound dressing have gained much attention.In this review,the recent advances in the development of flexible and wearable pH sensors for wound healing monitoring have been comprehensive summarized from the range of optical and electrochemical bases.

3-D Print Celulose Nanoskin: Future Diabetic Wound Healing

3D printing is the future. It will change the way in which we produce new materials—maybe much less in factories and much easier in shops. However, biobased materials have been difficult to 3D print. Most 3D printers use heat to melt the plastic or metal to be printed, and biobased materials are degraded. But cellulose nanofibrils have a solution to this problem: the printing paste is wet and dries out to a solid material. In this work, it was showed recent wound healing in Vinous Ulcer with kidney and other health complications using bacterial cellulose 3D print membranes.

Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients.Mesenchymal stem cells(MSCs)promote diabetic wound healing.Particularly when MSCs aggregate into multicellular spheroids,their therapeutic effect is enhanced.However,traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids,resulting in inefficiencies and inconveniences in MSC spheroid therapy.In this study,a three-dimensional porous nanofibrous dressing(NFD)is prepared using a combination of electrospinning and homogeneous freeze-drying.Using thermal crosslinking,the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility.Through the design of its structure and chemical composition,the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes,serving as MSC spheroid delivery systems for diabetic wound sites.Most importantly,MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor,basic fibroblast growth factor,and hepatocyte growth factor,thereby accelerating diabetic wound healing.The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.

Antimicrobial,antibiofilm,angiogenesis,anti-inflammatory,and wound healing activities of zinc nanoparticles green synthesized using Ferula macrecolea extract

Objective:To assess the antimicrobial,antibiofilm,anti-inflammatory,angiogenic,and wound healing activities of zinc nanoparticles(ZNPs)green synthesized using Ferula macrecolea extract.Methods:The green synthesis was conducted using the precipitation method.Then,the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),and minimum biofilm inhibition concentration 50%(MBIC50)of ZNPs against Staphylococcus aureus(S.aureus)and Pseudomonas aeruginosa(P.aeruginosa)were evaluated.The effects of ZNPs on the gene expressions of Staphylococcus spp.[intracellular adhesion A(icaA)and D(icaD)]and P.aeruginosa(rhlI and rhlR)were investigated using quantitative real-time PCR.In addition,the effects of ZNPs on wound healing,angiogenesis,and anti-inflammatory markers were assessed.Results:The green-synthesized ZNPs demonstrated significant antimicrobial efficacy against S.aureus and P.aeruginosa.The biofilm formation in S.aureus and P.aeruginosa was also inhibited by ZNPs with MBIC50 values of 3.30μg/mL and 2.08μg/mL,respectively.Additionally,ZNPs downregulated the expression of biofilm-related genes icaA,icaD,rhlI,and rhlR in the tested bacteria.They also demonstrated promising in vitro wound healing effects by promoting fibroblast cell proliferation and wound closure in a dose-dependent manner.A significant increase in the expression of HLA-G5 and VEGF-A genes as well as a marked decrease in the expression of NF-κB,IL-1β,and TNF-αgenes were observed in cells treated with ZNPs compared to the control group(P<0.05).Conclusions:ZNPs display promising antibacterial effects against S.aureus and P.aeruginosa and wound-healing effects by inhibiting biofilm formation,inducing angiogenesis,and reducing inflammation.However,further studies must be conducted to specify the accurate mechanisms of action and toxicity of ZNPs.

Single-cell sequencing technology in diabetic wound healing:New insights into the progenitors-based repair strategies

Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.

Biological scaffold as potential platforms for stem cells:Current development and applications in wound healing

Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Effect of recombinant human epidermal growth factor on porcine partial-thickness wound healing

Wound healing is a complex biologic event. Numerous growth factors are involved in the regulation of tissue repair and remodelling processes. In this study, several techniques were used to observe the effects of recombinant human epidermal growth factors (rh-EGF) on porcine partial-thickness burn wound healing. Healing rates of the burn wounds were quantitated by computer image analysis of the wound Pkotographs. Biopsies were taken for examining the cell DNA cycle by flow cytometry, and for observing the keratinocyte migration and degree of reepithelialization quantitated by anti-keratin antibodies. The results indicated that daily topical application of rh-EGF in suitable concentrations accelerated epithelial healing of partial-thickness burn wounds, and there was also a dose-dependent effect of rh-EGF on healing rates of the partial-thickness burn wounds.

Effects of Cold Atmospheric Pressure Plasma on Accelerating Acute Wound Healing: A Comparative Study among 4 Different Treatment Groups

Cold atmospheric pressure plasma (CAP) has been expected to be effective for wound healing among plasma medicines and has been attracting attention. The aim of this retrospective clinical study was to evaluate and compare the effects of CAP on acute wounds created by a fractional CO2 (FXCO2) laser on four treatment groups. Methods: This study was conducted between September 2017 and November 2018. Radiated surface wounds were created using a FXCO2 laser on four identically-sized regions on the medial side of the left forearm of 12 healthy volunteer subjects, for a total of 48 treatment regions. Each region was then randomly assigned to one of four groups: 1) no treatment (control group), 2) irradiated CAP for 60 seconds (plasma group), 3) topical application of ointment containing betamethasone valerate (steroid group), or 4) two to three sprays of basic fibroblast growth factor (bFGF group). The primary outcome of the skin was the change in absolute values of lightness index (L*), redness index (a*I) of L*a*b color space, arithmetical mean roughness (Ra), and mean melanin concentration. The secondary outcome was the clinical condition of the wounds, including inflammation, crust formation, and hyper/hypo-pigmentation on the recovering skin surface relative to the surrounding intact skin. Each item was evaluated at post-treatment 0, 1, 3, 7, 14, 28 days and 1 year. Results: Although no significant difference was observed among all groups, the CAP group exhibited more rapid recovery regarding a*I and Ra. No side-effects were observed in the CAP group. Conclusion: CAP is considered to accelerate healing of irradiated wounds via anti-inflammatory activity. Our study confirmed the effectiveness and safety of CAP which is devoid of side-effects of conventional therapies, and may aid in future development of medical plasma therapies.

Keladi candik(Alocasia longiloba Miq.) petiole extracts promote wound healing in a full thickness excision wound model in rats

Objective: To investigate the wound-healing effect of Alocasia longiloba(A. longiloba) petiole extract on wounds in rats.Methods: Twenty-two male Sprague-dawley rats were randomly assigned to receive 10% solcoseryl gel, phosphate buffer saline, 50% ethanol, 95% ethanol and hexane extracts of A. longiloba at 1.5%, 3% and 6% doses, respectively. A full thicknesses wound(6 mm) was created on the dorsal of the rat; and all rats were applied with the extract solutions, 10% solcoseryl gel and phosphate buffer saline once a day topically until day 12. The wound was photographed on day 1, 6 and 12, and the percentage of wound contraction was calculated. On day 12, rats were sacrificed and histological examination of granulation tissue was carried out using haematoxylin & eosin and Masson's Trichrome stain to determine the wound healing effect.Results: In this study, 6% of 50% and 95% ethanol extracts of A. longiloba showed 82.50% and 82.32% wound contraction, respectively, and were comparable with 10% solcoseryl gel(82.30%). Meanwhile, phosphate buffer saline treated group showed the lowest wound contraction(69.86%). Histological assessment of wound treated with 6% of 95% ethanol extract of A. longiloba showed distinct epidermal and dermal layer, higher proliferation of fibroblast and more angiogenesis with collagen compared to other wound treated groups.Conclusions: A. longiloba petiole extracts have a wound healing potential and 6% of 95% ethanol extract of A. longiloba is more effective. Further studies are required to understand the wound healing mechanism of action of the extract.

Wound healing activity of Abroma augusta in Wistar rats

Objective:The study was undertaken to evaluate the wound healing profile of alcoholic extract of Abroma augusta and its effect on dexamethasone suppressed wound healing in Wistar rats.Methods:An alcoholic extract of Abroma augusta was prepared.Three models were used - incision,excision and dead space wound models. Four groups of animals were used for each model.They were administered 2%gum acacia(orally),alcoholic extract of Abroma augusta(orally),dexamethasone(intramuscularly) and combination of Abroma augusta(orally) with dexamethasone(intramuscularly) respectively.The parameters studied included breaking strength of incision wound,period of epithelization and wound contraction rate in the excision wound,breaking strength,dry weight and hydroxyproline content of granulation tissue in dead space wound.Results:The breaking strength of incision wound of Abroma augusta treated group was significantly increased(P <0.001 ) while that of dexamethasone treated animals was significantly decreased(P<0.001) as compared to control. Coadministration of dexamethasone and Abroma augusta significantly reversed the dexamethasone suppressed wound healing in incision wound model(P< 0.001 ).Animals treated with both dexamethasone and Abroma augusta also showed significant(P <0.004) increase in the breaking strength of granulation tissue in the dead space wound and a significant(P <0.011) reduction in the period of epithelization in the excision wound as compared to rats treated with dexamethasone alone.The rate of wound contraction was not significantly altered in any of the groups.Conclusion:The alcoholic extract of Abroma augusta was found to reverse dexamethasone suppressed wound healing.

Regulatory T cells in skin regeneration and wound healing

As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue.Such temporally-and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation.In this context,regulatory T cells(Tregs)hold a key role in balancing immune homeostasis and mediating cutaneous wound healing.A comprehensive understanding of Tregs’multifaceted field of activity may help decipher wound pathologies and,ultimately,establish new treatment modalities.Herein,we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair.Further,we discuss how Tregs operate during fibrosis,keloidosis,and scarring.

Botulinum Toxin Type A and Its Possible Mechanisms on Wound Healing

Botulinum toxin type-A (BTX-A), a subtype from known seven types of botulinum neurotoxin (serotype A-G), is produced by a gram-positive bacterium, Clostridium botulinum. The toxin is now widely and efficiently used in treating a plethora of diverse symptoms and conditions. Recent evidence in the literature also shows that BTX-A exhibits a wide range of effects on non-neuronal cells. Its potential has markedly expanded to clinical applications other than the treatment of neurological and muscular conditions that are characterized by neuronal hyperactivity. A number of studies have shown BTX-A to improve the quality of scar outcome and prevent the formation of keloids and HTS. Although the mechanism of action of BTX-A on wound healing is still not clearly understood, lately there has been extensive research to grasp the underlying mechanisms of this multifunctional toxin. BTX-A seems to affect wound healing by a number of mechanisms that include action on tensile forces, inhibition of fibroblasts differentiation, downregulation of TGF-β1 and collagen expression. This review will explore the responses of Botulinum toxin type-A on wound healing and preventing pathological scars like HTS and keloids, and comprehend the overall effect BTX-A has on wound healing.

Macrophages:Key players in diabetic wound healing

In this editorial,we discuss the article by Wen et al published.Diabetic foot ulcers are prevalent and serious complications of diabetes,significantly impacting patients’quality of life and often leading to disability or death,thereby placing a heavy burden on society.Effective diabetic wound healing is hindered by an imbalance in macrophage polarization;many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,which is crucial for tissue remodelling and repair.The wound healing process is both dynamic and complex.Healthy M1 macrophages,which have strong phagocytic abilities,are vital during the inflammatory phase of diabetic wound healing.However,the failure to transition to M2 macrophages during the proliferative phase hinders wound healing.We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase,thereby enhancing the overall healing process.

Relevance of macrophages in the wound healing process among individuals afflicted with diabetic foot ulcers

In this paper,we provide a commentary on an article focusing on diabetic foot ulcer(DFU)as a dreadful complication of diabetes mellitus.The development of this condition is influenced by factors such as diabetic peripheral neuropathy,lower extremity artery disease,and infection.However,the underlying mecha-nism remains elusive.Macrophages play a critical role in wound healing proce-sses,suggesting that therapies targeting these cells could potentially improve the management of DFU.A comprehensive understanding of developmental trends of macrophages within the field of DFU may facilitate research advancements and the development of novel treatment strategies.