ON101 Cream Increases the Wound Healing Rate in Diabetic Patients with Uremia—Cases Report

Diabetic patients who underwent long-term dialysis may increase the prevalence of foot ulceration. In addition, diabetic foot ulcer (DFUs) patients with end-stage renal disease (ESRD) do not heal well, and the amputation rate is 6.5 - 10 times higher compared to the non-nephropathic diabetic population. Thus, a suitable therapeutic agent was needed. ON101 is a topical cream that promotes diabetic wound healing through a unique macrophage-regulating ability. In this case series, we included 5 diabetes patients (mean age 54.6 ± 8.7 years, 4 mal) with ESRD (mean eGFR 7.4 ± 3.35 mL/min/1.73m2) and had experienced dialysis for at least 4.5 years. These patients also have UT (University of Texas) grade 2A DFUs that have existed for at least 1.5 months (mean ulcer duration 8.3 ± 8.97 months). These subjects were applied ON101 twice daily for up to 20 weeks, and wound size was recorded during treatment. Among these subjects, three ulcers (patient No. 1, 2, and 3) completely healed within 10 weeks upon ON101 application, and one ulcer was 99% reduced at 20th weeks (patient No. 4). Only one ulcer didn’t show an obvious response that may due to poor compliance in wound care and glucose control. In summary, the overall healing rate was 60%, suggesting ON101 performed equivalence healing efficacy in dialysis patients compared with those who did not have dialysis.

A Skin-Inspired Self-Adaptive System for Temperature Control During Dynamic Wound Healing

The thermoregulating function of skin that is capable of maintaining body temperature within a thermostatic state is critical.However,patients suffering from skin damage are struggling with the surrounding scene and situational awareness.Here,we report an interactive self-regulation electronic system by mimicking the human thermos-reception system.The skin-inspired self-adaptive system is composed of two highly sensitive thermistors(thermal-response composite materials),and a low-power temperature control unit(Laserinduced graphene array).The biomimetic skin can realize self-adjusting in the range of 35–42℃,which is around physiological temperature.This thermoregulation system also contributed to skin barrier formation and wound healing.Across wound models,the treatment group healed~10%more rapidly compared with the control group,and showed reduced inflammation,thus enhancing skin tissue regeneration.The skin-inspired self-adaptive system holds substantial promise for nextgeneration robotic and medical devices.

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.

Advanced metal-organic frameworks-polymer platforms for accelerated dermal wound healing

Skin wound healing is an important aspect of regenerative medicine.Metal-organic frameworks(MOFs)have attracted considerable attention as promising nanomaterials for skin wound healing due to their remarkable versatility,tunable pore size,surface area,targeted delivery of various therapeutic agents,and controlled release properties.The combination of these materials with biocompatible and synthetic polymers can help improve their performance in wound regeneration.This review examines the potential of MOF-polymer composites in skin wound healing.Physical and biological chemical properties and methods of making MOFs and their composites have been investigated.In the final section of this review,challenges and future prospects for the development of MOF-polymer composites are stated.

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.

Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis

Diabetic wounds,characterized by prolonged inflammation and impaired vascularization,are a serious complication of diabetes.This study aimed to design a gelatin methacrylate(GelMA)hydrogel for the sustained release of netrin-1 and evaluate its potential as a scaffold to promote diabetic wound healing.The results showed that netrin-1 was highly expressed during the inflammation and proliferation phases of normal wounds,whereas it synchronously exhibited aberrantly low expression in diabetic wounds.Neutralization of netrin-1 inhibited normal wound healing,and the topical application of netrin-1 accelerated diabetic wound healing.Mechanistic studies demonstrated that netrin-1 regulated macrophage heterogeneity via the A2bR/STAT/PPARγsignaling pathway and promoted the function of endothelial cells,thus accelerating diabetic wound healing.These data suggest that netrin-1 is a potential therapeutic target for diabetic wounds.

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.

Thermosensitive and Wound-Healing Gelatin-Alginate Biopolymer Hydrogels Modified with Humic Acids

The main goal of the article is the creation and study of thermosensitive and wound-healing gelatin-alginate bio-polymer hydrogels modified with humic acids.Their rheological properties,swelling and contraction behavior were experimentally investigated,elucidated using Fourier transform infrared spectroscopy and used to achieve the physiological melting point,which is necessary for successful drug delivery.It has been shown that in the gelatin-alginate-humic acid biopolymer hydrogels systems,it is possible to obtain a gel-sol transition temperature close to the physiological temperature of 37°C,which is important for drug delivery in the treatment of wounds.By changing the type and concentration of humic acids in the gelatin-alginate hydrogel,it turned out to be achiev-able to regulate the softening time of the gel on the human body in the range from 6 to 20 min,which provides the possibility of controlled prolonged delivery of drugs.Based on the study of the influence of calcium ions on the properties of humic acids and ion exchange,as well as the interaction of humic acids,sodium alginate and gelatin with the formation of tighter gel networks,approaches to regulate the rate of softening of hydrogels at physiological temperature and their swelling,which simulates the absorption of exudate,were proposed and implemented.In addition,low shrinkage of the hydrogel surface due to cross-linking of gelatin-alginate networks when modified with humic acids was experimentally confirmed,which is important for avoiding problems of wound contracture and contour deformations when using dressings for wound healing.Thus,the developed opti-mized innovative biopolymer hydrogels synergistically combine the outstanding properties of natural molecular polymers and humic acids and are promising for the creation of effective medicines for wound healing.

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.

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.

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.

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.

Impact of tibial transverse transport in tissue regeneration and wound healing with perspective on diabetic foot ulcers

In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatment for patients with diabetic foot ulcers(DFU).TTT has been associated with tissue regeneration,improved blood circulation,reduced amputation rates,and increased expression of early angiogenic factors.Mechanistically,TTT can influence macrophage polarization and growth factor upregulation.Despite this potential,the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development.These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation,and blood vessel and bone marrow improvement.Immunomodu-lation via systemic responses contributes to its therapeutic potential.Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT.This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease.Here,we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.

Value of negative pressure sealing drainage on wound healing of Gustilo IIIB and IIIC open fractures

BACKGROUND Gustilo III fractures have a high incidence and are difficult to treat.Patients often experience difficulty in wound healing.Negative pressure drainage technology can help shorten wound healing time and has positive value in improving patient prognosis.AIM To explore the clinical value of the negative pressure sealing drainage technique in wound healing of Gustilo IIIB and IIIC open fractures.METHODS Eighty patients with Gustilo IIIB and IIIC open fractures with skin and soft tissue injuries who were treated in the Second People’s Hospital of Dalian from March 2019 to December 2021 were selected as the research subjects.They were divided into a study group(n=40,healed with negative pressure closed drainage)and a control group(n=40,healed with conventional dressing changes)according to the variation in the healing they received.The efficacy of the clinical interventions,the variations in the regression indicators(time to wound healing,time to fracture healing,time to hospitalization),and the conversion and healing of bacterial wounds were compared 1-3 mo after the intervention.RESULTS The total effective rate of patients among the study group was 95.00%(38/40),which was notably higher than 75.00%(30/40)among the control group(P<0.05).The wound healing time,fracture healing time,and hospital stay of the patients in the study group was shorter than the control group(P<0.05).After the intervention,the negative bacterial culture at the wound site rate and wound healing rate of the patients among the study group increased compared to the control group(P<0.05).CONCLUSION Negative pressure sealing and drainage technology has a good therapeutic effect on patients with Gustilo IIIB and IIIC open fracture wounds with skin and soft tissue injury.It can notably enhance the wound healing rate and the negative rate of bacteria on the wound surface and help to speed up the recovery process of patients.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway

BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence and development of DFU,focusing on the therapeutic mechanisms of X-Paste(XP)of wound healing in diabetic mice.METHODS Employing traditional Chinese medicine ointment preparation methods,XP combines various medicinal ingredients.High-performance liquid chromatography(HPLC)identified XP’s main components.Using streptozotocin(STZ)-induced diabetic,we aimed to investigate whether XP participated in the process of diabetic wound healing.RNA-sequencing analyzed gene expression differences between XP-treated and control groups.Molecular docking clarified XP’s treatment mechanisms for diabetic wound healing.Human umbilical vein endothelial cells(HUVECs)were used to investigate the effects of Andrographolide(Andro)on cell viability,reactive oxygen species generation,apoptosis,proliferation,and metastasis in vitro following exposure to high glucose(HG),while NF-E2-related factor-2(Nrf2)knockdown elucidated Andro’s molecular mechanisms.RESULTS XP notably enhanced wound healing in mice,expediting the healing process.RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment.HPLC identified 21 primary XP components,with Andro exhibiting strong Nrf2 binding.Andro mitigated HG-induced HUVECs proliferation,metastasis,angiogenic injury,and inflammation inhibition.Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation,with Nrf2 knockdown reducing Andro’s proliferative and endothelial protective effects.CONCLUSION XP significantly promotes wound healing in STZ-induced diabetic models.As XP’s key component,Andro activates the Nrf2/HO-1 signaling pathway,enhancing cell proliferation,tubule formation,and inflammation reduction.

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.

The Impact of Psychosocial Influences on Chronic Wound Healing

This comprehensive review explores the intricate dynamics between psychosocial factors and chronic wound healing processes, specifically focusing on prevalent conditions such as pressure ulcers, diabetic foot ulcers, and venous leg ulcers. By examining the roles of psychiatric conditions, including depression, anxiety, and post-traumatic stress disorder (PTSD), this paper illuminates how these factors intricately influence wound healing dynamics, including mechanisms of pain perception and inflammatory responses. Furthermore, we evaluate the effectiveness of integrated biopsychosocial interventions, which encompass a holistic approach to wound care, thereby enhancing healing outcomes for dermatology patients. Future studies should focus on investigating the specific psychosocial determinants that significantly influence wound healing, exploring novel therapeutic strategies, and implementing personalized interventions to meet the unique needs of each patient. Such endeavors hold promise in advancing the fields of psychodermatology and wound management, fostering a deeper understanding and application of psychosocial considerations in dermatological care.

Tamanu Oil in Acne Management: Potential Anti-Inflammatory and Wound-Healing Properties for Scar Reduction

Tamanu oil, derived from the nuts of Calophyllum inophyllum, has gained increasing attention for its potential in acne management due to its purported anti-inflammatory and wound-healing properties. This analysis evaluates the efficacy of tamanu oil in acne treatment with a specific focus on its impact on inflammation and scar reduction. The novelty of this research lies in its comprehensive analysis of tamanu oil’s dual mechanism of action: reducing acne-related inflammation and promoting the healing of acne scars. Clinical trials and laboratory analyses were conducted to assess the oil’s effectiveness in diminishing erythema, swelling, and post-acne scarring compared to conventional treatments. Preliminary findings demonstrate that tamanu oil significantly reduces inflammation and accelerates wound healing, potentially offering a promising adjunct or alternative to standard acne therapies. Future research should aim to optimize formulation and application protocols, long-term effects, and comparative therapeutic efficacy with other anti-inflammatory agents. Tamanu oil offers a novel and effective approach to acne management, with potential advantages that go beyond inflammation reduction to include enhanced scar reduction, making it a subject that warrants further investigation.

Antibacterial and angiogenic dual-functional fibrous membrane dressing for infected wound healing

Background:Skin,being a vital organ that regulates physiological responses in the human body,is prone to injury from external environmental factors.Healing full-thickness skin defects becomes especially challenging when infections and vascular injuries are involved.Traditional wound dressings with single functions,such as antibacterial or angiogenic properties,fall short in achieving rapid wound healing.To address this,there is a need to develop wound dressing materials that possess both effective antibacterial and angiogenic properties.Methods:In this study,we utilized electrospinning technology to fabricate hyaluronic acid-cellulose acetate fibrous membrane dressings,incorporating poly(ionic liquid)as an antibacterial polymer and deferoxamine as an angiogenic agent.Results:The resulting fibrous membrane dressing contained poly(ionic liquid)and deferoxamin showcased a microporous structure,drug-releasing capabilities,and excellent air permeability.It not only demonstrated highly effective antibacterial properties but also exhibited remarkable angiogenesis,thereby promoting the healing of full-thickness skin defect wounds in both in vitro and in vivo assays.Conclusion:These findings highlight the immense potential of this wound dressing material for future clinical applications.

Janus hydrogel/electrospun-membrane dressing enhancing wound healing in rats

Background:Excessive exudate secreted from chronic wounds often leads to overhydration and infection.Although a variety of dressings are currently available in clinical applications,they frequently fail to provide multifunction to promote chronic wound healing.The dressings with a Janus structure,featuring distinct properties on each side,are potential to improve wound healing.Methods:Composite dressings with a Janus structure were fabricated,comprising freeze-dried polycaprolactone(PCL)electrospun membrane and alginate-based hydrogel.The PCL fibrous membrane provided air permeability,while the hydrogel loaded with Deferoxamine,composed of alginate and poly(N-isopropylacrylamide)(PNIPAM),exhibited hygroscopic properties.The inclusion of PNIPAM imparted thermo-responsivity.Results:The hydrogel(thickness of 2.778±0.082 mm)exhibited a robust adhesion to the fiber membrane(thickness of 0.261±0.041 mm).For ANDC(Alginate-PNIPAM hydrogel with Deferoxamine/PCL membrane)samples,the water vapor transmission rate(WVTR)was measured to be 3364.80±23.23 g∙m−2∙day−1 and the swelling ratio at 2 h was determined to be 1179±125%.The thermo-responsivity of ANDC samples manifested in an increased swelling rate,escalating from 797±189%at 37°C to 1132±147%at 4°C.The elastic modulus was assessed for lyophilized and rehydrated ANDC sample.When theωof the rheometer rotor was decreased from 10 rad/s to 0.1 rad/s,the lyophilized dressing exhibited a decrease from 2.65±0.01 MPa to 1.80±0.90 MPa,while the rehydrated dressing demonstrated an increase from 133.65±55.68 Pa to 264.23±141.71 Pa.The pro-healing properties of the dressings were evaluated using full-thickness skin defect model on SD rats,and a circular wound of diameter 10 mm healed completely by day 12.Conclusion:The dressings not only protected the wound and absorbed excess exudate,but also demonstrated nondestructive peelability upon cooling,providing a novel approach for accelerating wound healing and management.