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.

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.

Prevalence and risk factors of wound complications after transtibial amputation in patients with diabetic foot

BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infection.AIM To analyze the prognosis and risk factors related to wound complications after transtibial amputation in patients with diabetes.METHODS This retrospective cohort study included seventy-two patients with DMF complications who underwent transtibial amputation between April 2014 and March 2023.The groups were categorized based on the occurrence of wound complications,and we compared demographic data between the complication group and the non-complication group to analyze risk factors.Moreover,a multivariate logistic regression analysis was performed to identify risk factors.RESULTS The average follow-up period was 36.2 months.Among the 72 cases,31(43.1%)had wound complications.Of these,12 cases(16.7%)received further treatment,such as debridement,soft tissue stump revision,and re-amputation at the proximal level.In a group that required further management due to wound complications after transtibial amputation,the hemoglobin A1c(HbA1c)level was 9.32,while the other group that did not require any treatment had a 7.54 HbA1c level.The prevalence of a history of kidney transplantation with wound complications after transtibial amputation surgery in DMF patients was significantly greater than in cases without wound complications(P=0.02).Other factors did not show significant differences.CONCLUSION Approximately 43.1%of the patients with transtibial amputation surgery experienced wound complications,and 16.7%required additional surgical treatment.High HbA1c levels and kidney transplant history are risk factors for postoperative wound complications.

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.

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.

Therapeutic role of growth factors in treating diabetic wound

Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.

Non-surgical treatment of diabetic foot ulcers on the dorsum of the foot with polydeoxyribonucleotide injection:Two case reports

BACKGROUND Diabetic foot ulcers are caused by a variety of factors,including peripheral neuropathy,peripheral arterial disease,impaired wound healing mechanisms,and repetitive trauma.Patients with diabetic foot ulcer on the dorsum of the foot are often treated surgically.However,the right non-surgical therapy must be chosen if surgical choices are contraindicated or if the patient prefers conservative treatment over surgery.CASE SUMMARY The purpose of this case report is to highlight the efficacy of polydeoxyribonucleotide(PDRN)injection as a non-surgical treatment option for diabetic foot ulcers on the dorsum of the foot,particularly in patients who choose against surgical intervention.This case report presents two cases of diabetic foot ulcers located on the dorsum of the foot that were successfully treated with PDRN injection as a non-surgical intervention.CONCLUSION If the patient declines surgery for diabetic ulcers with Wagner grade II or below,PDRN injection can be effective if necrotic tissue is removed and the wound bed kept clean.

Adipose-derived stem cells in diabetic foot care:Bridging clinical trials and practical application

Diabetic foot ulcers(DFUs)pose a critical medical challenge,significantly impairing the quality of life of patients.Adipose-derived stem cells(ADSCs)have been identified as a promising therapeutic approach for improving wound healing in DFUs.Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU,its clinical applications remain elusive.In this review,we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs.The review begins with a discussion of the classification and clinical management of diabetic foot conditions.It then discusses the current landscape of clinical trials,focusing on their geographic distribution,reported efficacy,safety profiles,treatment timing,administration techniques,and dosing considerations.Finally,the review discusses the preclinical strategies to enhance ADSC efficacy.This review shows that many trials exhibit biases in study design,unclear inclusion criteria,and intervention protocols.In conclusion,this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches,with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

Clinical comprehensive treatment protocol for managing diabetic foot ulcers:A retrospective cohort study

BACKGROUND Diabetic foot ulcers(DFUs)are a common complication of diabetes,often leading to severe infections,amputations,and reduced quality of life.The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications.A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs.The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing,reduced amputation rates,and improved overall patient outcomes compared to standard treatment protocols.AIM To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol.METHODS This retrospective study included 62 patients with DFUs,enrolled between January 2022 and January 2024,randomly assigned to the experimental(n=32)or control(n=30)group.The experimental group received a comprehensive treatment comprising blood circulation improvement,debridement,vacuum sealing drainage,recombinant human epidermal growth factor and anti-inflammatory dressing,and skin grafting.The control group received standard treatment,which included wound cleaning and dressing,antibiotics administration,and surgical debridement or amputation,if necessary.Time taken to reduce the white blood cell count,number of dressing changes,wound healing rate and time,and amputation rate were assessed.RESULTS The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate,wound healing time,and amputation rate.Additionally,the comprehensive treatment protocol was safe and well tolerated by the patients.CONCLUSION Comprehensive treatment for DFUs is more effective than standard treatment,promoting granulation tissue growth,shortening hospitalization time,reducing pain and amputation rate,improving wound healing,and enhancing quality of life.

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.

Mechanisms of medicinal plants in the treatment of diabetic wound

Wound repair is noticeably prolonged in a diabetic state due to a faulty inflammatory process and an underlying neuropathy.Several medicinal plants and their products have been of prime importance for the management of wounds over the years.Various mechanisms whereby medicinal plants elicit their action in wound repair are revealed and some plants are proven to be experimentally effective in enhancing wound closure and achieving healing.The mechanisms identified include hyperglycemic control,alleviation of physiological inflammation,controlled oxidative stress,infection control,and influence on gene expression.Information in this review was sourced from research and review articles in electronic databases such as Web of Science,Scopus,PubMed,and Google Scholar.

Progress and expectation of stem cell therapy for diabetic wound healing

Impaired wound healing presents great health risks to diabetics.Encouragingly,the current clinical successfully found out meaningful method to repair wound tissue,and stem cell therapy could be an effective method for diabetic wound healing with its ability to accelerate wound closure and avoid amputation.This minireview aims at introducing stem cell therapy for facilitating tissue repair in diabetic wounds,discussing the possible therapeutic mechanism and clinical application status and problems.

Diabetic wounds and artificial intelligence:A mini-review

Diabetic wound takes longer time to heal due to micro and macro-vascular ailment.This longer healing time can lead to infections and other health complications.Foot ulcers are one of the most common diabetic wounds.These are one of the leading cause of amputations.Medical science is continuously striving for improving quality of human life.A recent trend of amalgamation of knowledge,efforts and technological advancement of medical science experts and artificial intelligence researchers,has made tremendous success in diagnosis,prognosis and treatment of a variety of diseases.Diabetic wounds are no exception,as artificial intelligence experts are putting their research efforts to apply latest technological advancements in the field to help medical care personnel to deal with diabetic wounds in more effective manner.The presented study reviews the diagnostic and treatment research under the umbrella of Artificial Intelligence and computational science,for diabetic wound healing.Framework for diabetic wound assessment using artificial intelligence is presented.Moreover,this review is focused on existing and potential contribution of artificial intelligence to improve medical services for diabetic wound patients.The article also discusses the future directions for the betterment of the field that can lead to facilitate both,clinician and patients.

Revolutionizing diabetic wound healing:The power of microneedles

Diabetic wounds significantly affect patient quality of life.Microneedles are a promising treatment to accelerate wound healing owing to their high drug-loading capacity and efficient drug delivery;however,few studies to date have comprehensively reviewed microneedles for diabetic wound healing.This up-to-date review summarizes the research progress in microneedles for diabetic wound healing,including manufacturing materials and techniques,structures,designs,release mechanisms,delivery substances,and their specific effects.This study showed that most microneedles designed for diabetic wounds are made of synthetic polymers and/or natural materials using polydimethylsiloxane micromolding.The geometric structure and design directly influence penetration ability and drug delivery capacity.Microneedles can deliver antibiotics,hypoglycemic agents,traditional Chinese medicines,metal ions,growth factors,exosomes,stem cells,and microorganisms,thus promoting diabetic wound healing through diverse mechanisms,such as antibacterial,anti-inflammatory,antioxidant,hypoglycemic,and angiogenic activities,at different stages of the healing process.In conclusion,microneedles are promising drug delivery systems for the treatment of diabetic wounds.

Effectiveness of topical oxygen therapy in wound healing for patients with diabetic foot ulcer

Objectives:Non-healing wounds have been one of the major challenges in health care because of increased morbidity,especially for those who have diabetes mellitus.Numerous regimens are being innovated to produce an evidence-based practice that would minimize complications and promote healing.Topical oxygen therapy is an innovation in wound care that has been considered influential in the wound healing process.This intervention aims to increase the oxygen concentration in the affected limb to promote wound healing.Methods:This research applied an experimental design that targeted a total of 60 adult patients aged 45–64 years with diabetic foot ulcers.A randomized systematic sampling technique was used to allow equal chances and prevent bias.In total,30 patients in the control group received usual care for diabetic foot ulcers,and the remaining 30 patients in the experimental group received topical oxygen therapy together with standard care for diabetic foot ulcers.Subjects were assessed using the Wagner-Meggitt Wound Classification System.Results:The result proved that there was a significant difference in the wound grade of patients in the experimental group after the application of the usual wound care plus the topical oxygen therapy using Friedman's test.The control and experimental groups were compared using Mann–Whitney statistical analyses,and the results showed that there was a significant difference between the control and experimental groups after the application of topical oxygen therapy.Conclusions:Topical oxygen therapy was demonstrated to be effective to aid in the wound healing process of patients with diabetic foot ulcers.Fur ther research was recommended to improve the application of topical oxygen therapy to patients with chronic wounds and promote the wound healing process.

Current scenario of traditional medicines in management of diabetic foot ulcers:A review

Diabetic foot infections and diabetic foot ulcers(DFU)cause significant suffering and are often recurring.DFU have three important pathogenic factors,namely,microangiopathy causing local tissue anoxia,neuropathy making the foot prone to injuries from trivial trauma,and local tissue hyperglycaemia favouring infection and delaying the wound healing.DFU have been the leading cause for non-traumatic amputations of part or whole of the limb.Western medicines focus mainly on euglycaemia,antimicrobials,debridement and wound cover with grafts,and off-loading techniques.Advances in euglycaemic control,foot care and footwear,systemic antimicrobial therapy,and overall health care access and delivery,have resulted in an overall decrease in amputations.However,the process of wound care after adequate debridement remains a major cost burden globally,especially in developing nations.This process revolves around two basic concerns regarding control/eradication of local infection and promotion of faster healing in a chronic DFU without recurrence.Wound modulation with various dressings and techniques are often a costly affair.Some aspects of the topical therapy with modern/Western medicines are frequently not addressed.Cost of and compliance to these therapies are important as both the wounds and their treatment are“chronic.”Naturally occurring agents/medications from traditional medicine systems have been used frequently in different cultures and nations,though without adequate clinical base/relevance.Traditional Chinese medicine involves restoring yin-yang balance,regulating the‘chi’,and promoting local blood circulation.Traditional medicines from India have been emphasizing on‘naturally’available products to control wound infection and promote all the aspects of wound healing.There is one more group of chemicals which are not pharmaceutical agents but can create acidic milieu in the wound to satisfy the above-mentioned basic concerns.Various natural and plant derived products(e.g.,honey,aloe vera,oils,and calendula)and maggots are also used for wound healing purposes.We believe that patients with a chronic wound are so tired physically,emotionally,and financially that they usually accept native traditional medicine which has the same cultural base,belief,and faith.Many of these products have never been tested in accordance to“evidence-based medicine.”There are usually case reports and experience-based reports about these products.Recently,there have been some trials(in vitro and in vivo)to verify the claims of usage of traditional medicines in management of DFU.Such studies show that these natural products enhance the healing process by controlling infection,stimulating granulation tissue,antimicrobial action,promoting fibroblastic activity and collagen deposition,etc.In this review,we attempt to study and analyse the available literature on results of topical traditional medicines,which are usually advocated in the management of DFU.An integrated and‘holistic’approach of both modern and traditional medicine may be more acceptable to the patient,cost effective,and easy to administer and monitor.This may also nevertheless lead to further improvement in quality of life and decrease in the rates of amputations for DFU.

Mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer:A review

The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

Effect of Bismuth Subgallate/Borneol Combined with Autologous Platelet-Rich Gel in the Treatment of Patients with Diabetic Foot Ulcers

Objective: To explore the effect of Bismuth Subgallate/Borneol (SuileTM BSB) healing dressing combined with autologous platelet-rich gel (APG) in the treatment of diabetic foot ulcer (DFU). Methods: A total of 120 patients with DFU hospitalized in the Changsha Central Hospital from August 2020 to September 2021 were selected and randomly divided into an experimental group (BSB + APG, n = 60) and a control group (BSB, n = 60) according to random number table method. The total therapeutic effect, healing time, hospital stay, level indexes of various inflammatory factors before and after treatment and ulcer area were observed in the two groups. Results: The total effect of the control group was worse than that of the experimental group, and the data between the two groups were significant (P 0.05);after treatment, the levels of inflammatory factors including WBC, CRP, IL-6 and TNF-α in the control group were higher than those in the experimental group, and there was significant difference between the two groups (P 0.05);after 14 days of treatment, the ulcer area in the control group was larger than that in the experimental group, and the data between the two groups were significant (P Conclusion: BSB combined with APG can achieve better therapeutic effect, reduce the inflammatory reaction of patients, and promote wound healing in the treatment of patients with diabetic foot ulcer.

Management of negative pressure wound therapy in the treatment of diabetic foot ulcers

Diabetic foot(DF) is a common complication of diabetes and the first cause of hospital admission in diabetic patients. In recent years several guidelines have been proposed to reinforce the the management of DF with a notable increase in diabetes knowledge and an overall reduction of amputations. Significant improvements have been reached in the treatment of diabetic foot ulcers(DFUs) and nowadays clinicians have several advanced medications to apply for the best local therapy. Among these, negative pressure wound therapy(NPWT) is a useful adjunct in the management of chronic and complex wounds to promote healing and wound bed preparation for surgical procedures such as skin grafts and flap surgery. NPWT has shown remarkable results although its mechanisms of action are not completely understood. In this paper, we offer a complete overview of this medication and its implication in the clinical setting. We have examined literature related to NPWT concerning human, animal and in vitro studies, and we have summarized why, when and how we can use NPWT to treat DFUs. Further we have associated our clinical experience to scientific evidence in the field of diabetic foot to identify a defined strategy that could guide clinician in the use of NPWT approaching to DFUs.

Choice of wound care in diabetic foot ulcer: A practical approach

Diabetic foot ulcers are the consequence of multiple factors including peripheral neuropathy,decreased blood supply,high plantar pressures,etc.,and pose a significant risk for morbidity,limb loss and mortality.The critical aspects of the wound healing mechanism and host physiological status in patients with diabetes necessitate the selection of an appropriate treatment strategy based on the complexity and type of wound.In addition to systemic antibiotics and surgical intervention,wound care is considered to be an important component of diabetic foot ulcer management.This article will focus on the use of different wound care materials in diabetic foot.From a clinical perspective,it is important to decide on the wound care material depending on the type and grade of the ulcer.This article will also provide clinicians with a simple approach to the choice of wound care materials in diabetic foot ulcer.