Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives

BACKGROUND Stem cell therapy has shown great potential for treating diabetic foot(DF).AIM To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades,with the aim of depicting the current global research landscape,identifying the most influential research hotspots,and providing insights for future research directions.METHODS We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF.Bibliometric analysis was carried out using CiteSpace,VOSviewer,and R(4.3.1)to identify the most notable studies.RESULTS A search was conducted to identify publications related to the use of stem cells for DF treatment.A total of 542 articles published from 2000 to 2023 were identified.The United States had published the most papers on this subject.In this field,Iran’s Shahid Beheshti University Medical Sciences demonstrated the highest productivity.Furthermore,Dr.Bayat from the same university has been an outstanding researcher in this field.Stem Cell Research&Therapy is the journal with the highest number of publications in this field.The main keywords were“diabetic foot ulcers,”“wound healing,”and“angiogenesis.”CONCLUSION This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years.Current research findings suggested that the hotspots in this field include stem cell dressings,exosomes,wound healing,and adipose-derived stem cells.Future research should also focus on the clinical translation of stem cell therapies for DF.

Academic productivity correlates with industry earnings in foot and ankle fellowship programs in the United States:A retrospective analysis

BACKGROUND The study investigates the connection between academic productivity and industry earnings in foot and ankle orthopedic surgery fellowships.Utilizing metrics like the H-index and Open Payments Database(OPD)data,it addresses a gap in understanding the relationship between scholarly achievements and financial outcomes,providing a basis for further exploration in this specialized medical field.AIM To elucidate the trends between academic productivity and industry earnings across foot and ankle orthopedic surgery fellowship programs in the United States.METHODS This study is a retrospective analysis of the relationship between academic productivity and industry earnings of foot and ankle orthopedic surgery fellowships at an individual faculty and fellowship level.Academic productivity was defined via H-index and recorded from the Scopus website.Industry earnings were recorded from the OPD.RESULTS Forty-eight foot and ankle orthopedic surgery fellowships(100%of fellowships)in the United States with a combined total of 165 physicians(95.9%of physicians)were included.Mean individual physician(n=165)total life-time earnings reported on the OPD website was United States Dollar(USD)451430.30±1851084.89(range:USD 25.16-21269249.85;median:USD 27839.80).Mean physician(n=165)H-index as reported on Scopus is 14.24±12.39(range:0-63;median:11).There was a significant but weak correlation between individual physician H-index and individual physician total life-time earnings(P<0.001;Spearman’s rho=0.334)and a significant and moderate positive correlation between combined fellowship H-index and total life-time earnings per fellowship(P=0.004,Spearman’s rho=0.409).CONCLUSION There is a significant and positive correlation between academic productivity and industry earnings at foot and ankle orthopedic surgery fellowships in the United States.This observation is true on an individual physician level as well as on a fellowship level.

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.

Surgical management of the diabetic foot:The current evidence

The prevalence of diabetes mellitus and its associated complications,particularly diabetic foot pathologies,poses significant healthcare challenges and economic burdens globally.This review synthesises current evidence on the surgical management of the diabetic foot,focusing on the interplay between neuropathy,ischemia,and infection that commonly culminates in ulcers,infections,and,in severe cases,amputations.The escalating incidence of diabetes mellitus underscores the urgency for effective management strategies,as diabetic foot complications are a leading cause of hospital admissions among diabetic patients,significantly impacting morbidity and mortality rates.This review explores the pathophysiological mechanisms underlying diabetic foot complications and further examines diabetic foot ulcers,infections,and skeletal pathologies such as Charcot arthropathy,emphasising the critical role of early diagnosis,comprehensive management strategies,and interdisciplinary care in mitigating adverse outcomes.In addressing surgical interventions,this review evaluates conservative surgeries,amputations,and reconstructive procedures,highlighting the importance of tailored approaches based on individual patient profiles and the specific characteristics of foot pathologies.The integration of advanced diagnostic tools,novel surgical techniques,and postoperative care,including offloading and infection control,are discussed in the context of optimising healing and preserving limb function.

Acute effect of foot strike patterns on in vivo tibiotalar and subtalar joint kinematics during barefoot running

Background:Foot kinematics,such as excessive eversion and malalignment of the hindfoot,are believed to be associated with running-related injuries.The maj ority of studies to date show that different foot strike patterns influence these specific foot and ankle kinematics.However,technical deficiencies in traditional motion capture approaches limit knowledge of in vivo joint kinematics with respect to rearfoot and forefoot strike patterns(RFS and FFS,respectively).This study uses a high-speed dual fluoroscopic imaging system(DFIS)to determine the effects of different foot strike patterns on 3D in vivo tibiotalar and subtalar joints kinematics.Methods:Fifteen healthy male recreational runners underwent foot computed tomography scanning for the construction of 3-dimensional models.A high-speed DFIS(100 Hz)was used to collect 6 degrees of freedom kinematics for participants’tibiotalar and subtalar joints when they adopted RFS and FFS in barefoot condition.Results:Compared with RFS,FFS exhibited greater internal rotation at 0%-20%of the stance phase in the tibiotalar joint.The peak internal rotation angle of the tibiotalar joint under FFS was greater than under RFS(p<0.001,Cohen’s d=0.92).RFS showed more dorsiflexion at 0%-20%of the stance phase in the tibiotalar joint than FFS.RFS also presented a larger anterior translation(p<0.001,Cohen’s d=1.28)in the subtalar joint at i nitial contact than FFS.Conclusion:Running with acute barefoot FFS increases the internal rotation of the tibiotalar joint in the early stance.The use of high-speed DFIS to quantify the movement of the tibiotalar and subtalar joint was critical to revealing the effects of RF S and FFS during running.

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.

Foot and ankle surgery:Tourniquet placement site to cause as little postoperative pain as possible

There is controversy in the literature on where to place the tourniquet(thigh,calf,ankle)for foot and ankle surgery.While some authors prefer the ankle tourniquet to the calf tourniquet,others state that the surgeon can decide between using the thigh tourniquet or the ankle tourniquet,since there was no difference in postoperative pain between them.Where to place the tourniquet during foot and ankle surgery to cause the least possible postoperative pain to the patient as a result of the tourniquet is a common question in clinical practice.The reality is that,unfortunately,there is no consensus on this issue.Perhaps the only possible way to answer this question would be to conduct a comparative study with sufficient statistical power to reach scientifically sound conclusions.It does not seem easy to carry out such a study,but it would be important to be able to answer the question posed in the title of this Editorial once and for all.

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.

Home-based Detection and Prediction of Diabetic Foot Ulcers at Early Stage Using Sensor Technology and Supervised Learning

For years,foot ulcers linked with diabetes mellitus and neuropathy have significantly impacted diabetic patients’ health-related quality of life(HRQoL). Diabetes foot ulcers impact15% of all diabetic patients at some point in their lives. The facilities and resources used for DFU detection and treatment are only available at hospitals and clinics,which results in the unavailability of feasible and timely detection at an early stage. This necessitates the development of an at-home DFU detection system that enables timely predictions and seamless communication with users,thereby preventing amputations due to neglect and severity. This paper proposes a feasible system consisting of three major modules:an IoT device that works to sense foot nodes to send vibrations onto a foot sole,a machine learning model based on supervised learning which predicts the level of severity of the DFU using four different classification techniques including XGBoost,K-SVM,Random Forest,and Decision tree,and a mobile application that acts as an interface between the sensors and the patient. Based on the severity levels,necessary steps for prevention,treatment,and medications are recommended via the application.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers

BACKGROUND Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability,traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method.AIM To investigate whether Huangma Ding or autologous platelet-rich gel(APG)treatment would benefit diabetic lower extremity arterial disease(LEAD)patients with foot ulcers.METHODS A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups:Group A(62 patients;basal treatment),Group B(38 patients;basal treatment and APG),and Group C(55 patients;basal treatment and Huangma Ding).All patients underwent routine follow-up visits for six months.After follow-up,we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters.RESULTS The infection status of the three groups before treatment was the same.Procalcitonin(PCT)improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B.Logistic regression analysis revealed that PCT was positively correlated with total amputation,primary amputation,and minor amputation rates.The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A.The major amputation rate,minor amputation rate,and total amputation times in Groups B and C were lower than those in Group A.CONCLUSION Our research indicated that diabetic foot ulcers(DFUs)lead to major amputation,minor amputation,and total amputation through local infection and poor microcirculation and macrocirculation.Huangma Ding and APG were effective attreating DFUs.The clinical efficacy of Huangma Ding was better than that of autologous platelet gel,which may be related to the better control of local infection by Huangma Ding.This finding suggested that in patients with DFUs combined with coinfection,controlling infection is as important as improving circulation.

Expression and clinical significance of pattern recognition receptor-associated genes in hand, foot and mouth disease

Objective:To explore which pattern recognition receptors(PRRs)play a key role in the development of hand,foot,and mouth disease(HFMD)by analyzing PRR-associated genes.Methods:We conducted a comparative analysis of PRR-associated gene expression in human peripheral blood mononuclear cells(PBMCs)infected with enterovirus 71(EV-A71)which were derived from patients with HFMD of different severities and at different stages.A total of 30 PRR-associated genes were identified as significantly upregulated both over time and across different EV-A71 isolates.Subsequently,ELISA was employed to quantify the expression of the six most prominent genes among these 30 identified genes,specifically,BST2,IRF7,IFI16,TRIM21,MX1,and DDX58.Results:Compared with those at the recovery stage,the expression levels of BST2(P=0.027),IFI16(P=0.016),MX1(P=0.046)and DDX58(P=0.008)in the acute stage of infection were significantly upregulated,while no significant difference in the expression levels of IRF7(P=0.495)and TRIM21(P=0.071)was found between different stages of the disease.The expression levels of BST2,IRF7,IFI16 and MX1 were significantly higher in children infected with single pathogen than those infected with mixed pathogens,and BST2,IRF7,IFI16 and MX1 expression levels were significantly lower in coxsackie B virus(COXB)positive patients than the negative patients.Expression levels of one or more of BST2,IRF7,IFI16,TRIM21,MX1 and DDX58 genes were correlated with PCT levels,various white blood cell counts,and serum antibody levels that reflect disease course of HFMD.Aspartate aminotransferase was correlated with BST2,MX1 and DDX58 expression levels.Conclusions:PRR-associated genes likely initiate the immune response in patients at the acute stage of HFMD.

The Effect of Transverse Tibial Bone Transfer in the Treatment of Diabetic Foot

To analyse the effectiveness of performing a transverse tibial bone graft in the treatment of patients with diabetic foot. We retrospectively analysed the clinical details of 51 diabetic foot patients in our hospital from February 2023 to February 2024 and divided them into two groups according to the different treatment modalities, in which the control group received open debridement and the treatment group received transverse tibial bone transfer and compared the differences between the two groups. There were large differences in VAS score, Toronto Clinical Symptom Score, quality of life score, internal lumen diameter, blood flow velocity in the affected limb, perfusion volume, vascular endothelial growth factor, epidermal growth factor and CRP between the two groups after surgery (P < 0.05). Patients with diabetic foot should be treated with transverse tibial bone grafting, which is safer and more effective and can have a significant impact on improving the status of the affected limb, the inflammation and the patient’s quality of life.

Use of Topical Complementary and Alternative Medicines (CAM) in Diabetic Septic Foot Disease in Makkah Region, Western of Saudi Arabia, an Exploratory Study

Diabetes is a chronic condition that is significantly impacted daily by environment. At least one in five Saudis, suffer from diabetes. “Diabetes is a pandemic of unprecedented magnitude spiraling out of control” (Boulton). Saudi Arabia ranks the second highest in the Middle East, and is the seventh in the world for the prevalence of diabetes (WHO). Diabetes mellitus (DM) has been found to be related to high mortality, morbidity accompanied by poor general health and lower quality of life. Current Saudi diabetes patients’ behaviors, practices, and beliefs regarding foot health problems such as ulcers, are not well investigated. Diabetic patients frequently utilize natural remedies and Herbs for self-medication as a part of complementary and alternative Medicine. Aim of study: To explore the widespread use of the alternative remedies in the local communities of the Western Saudi Arabia, the drives behind using and to focus on the potential adverse effects following their usage. Method: A descriptive, cross-sectional study of 386 diabetic patients with feet problems in Makkah Region, West of Saudi Arabia during the period April - June 2023. Results: Out of the 531 participants, only 386 participants reported diabetic foot disorder (DFD). Most of the participant were above 65 years of age group (24.61 %). Male (52.08%) more than female (47.92%) in the research group. All of the participants had diabetic foot disorders at least once. The prevalence of complementary and alternative medicines (CAM) use among them was 67.88%, as solitary or in combination with hospital medicines. Honey headed the list followed by myrrh and black seeds. Acquaintances advice (59.54%) was the most reason for using the alternative medicine. 60.30% of Diabetic foot patient complained of adverse effects during CAM remedies use. Conclusion: Consumption of CAM remedies among diabetic patients for Diabetic Foot Disorder (DFD) is common. Honey headed the list followed by myrrh and black seeds. Additional wide-scale research is required to establish their actual efficacy, safety and potential adverse out-comes and to generalize the outcomes.

Nonlinear Pushover Analysis of the Influences on RC Footing for the External Elevator Well

In contemporary society, reducing carbon dioxide emissions and achieving sustainable development are paramount goals. One effective approach is to preserve existing RC (Reinforced Concrete) buildings rather than demolishing them for new construction. However, a significant challenge arises from the lack of elevator designs in many of these existing RC buildings. Adding an external elevator becomes crucial to solving accessibility issues, enhancing property value, and satisfying modern residential buildings using convenient requirements. However, the structural performance of external elevator wells remains understudied. This research is designed by the actual external elevator project into existing RC buildings in Jinzhong Rd, Shanghai City. Specifically, this research examines five different external elevator wells under nonlinear pushover analysis, each varying in the height of the RC (Reinforced Concrete) footing. By analyzing plastic hinge states, performance points, capacity curves, spectrum curves, layer displacement, and drift ratio, this research aims to provide a comprehensive understanding of how these structures of the external elevator well respond to seismic events. The findings are expected to serve as a valuable reference for future external elevator projects, ensuring the external elevator designs meet the seismic requirements. By emphasizing seismic resistance in the design phase, the research aims to enhance the overall safety and longevity of external elevator systems integrated into existing RC buildings.

Transmission Dynamics and Optimal Control Strategies of a Hand-Foot-Mouth Disease Model with Treatment and Vaccination Interventions

In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.

Understanding the multifaceted etiopathogenesis of foot complications in individuals with diabetes

Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients.The aim of this study is to provide an evidence-based overview of diabetic foot complications.Due to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin lesions.In patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and amputations.Hyperglycemia compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound healing.In addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance.As a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be overlooked.Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed annually.Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.

Detection,management,and prevention of diabetes-related foot disease in the Australian context

Diabetes-related foot disease(DFD)is a widely feared complication among people who live with diabetes.In Australia and globally,rates of disability,cardiovascular disease,lower extremity amputation,and mortality are significantly increased in patients with DFD.In order to understand and prevent these outcomes,we analyse the common pathogenetic processes of neuropathy,arterial disease,and infection.The review then summarises important management considerations through the interdisciplinary lens.Using Australian and international guidelines,we offer a stepwise,evidence-based practical approach to the care of patients with DFD.

Examining the intrinsic foot muscles'capacity to modulate plantar flexor gearing and ankle joint contributions to propulsion in vertical jumping

Background:During human locomotion,a sufficiently stiff foot allows the ankle plantar flexors to generate large propulsive powers.Increasing foot stiffness(e.g.,via a carbon plate)increases the ankle’s external moment arm in relation to the internal moment arm(i.e.,increasing gear ratio),reduces plantar flexor muscles’shortening velocity,and enhances muscle force production.In contrast,when activation of the foot’s intrinsic muscles is impaired,there is a reduction in foot and ankle work and metatarsophalangeal joint stiffness.We speculated that the reduced capacity to actively control metatarsophalangeal joint stiffness may impair the gearing function of the foot at the ankle.Methods:We used a tibial nerve block to examine the direct effects of the intrinsic foot muscles on ankle joint kinetics,in vivo medial gastrocnemius’musculotendinous dynamics,and ankle gear ratio on 14 participants during maximal vertical jumping.Results:Under the nerve block,the internal ankle plantar flexion moment decreased(p=0.004)alongside a reduction in external moment arm length(p=0.021)and ankle joint gear ratio(p=0.049)when compared to the non-blocked condition.Although medial gastrocnemius muscle-tendon unit and fascicle velocity were not different between conditions,the Achilles tendon was shorter during propulsion in the nerve block condition(p<0.001).Conclusion:In addition to their known role of regulating the energetic function of the foot,our data indicate that the intrinsic foot muscles also act to optimize ankle joint torque production and leverage during the propulsion phase of vertical jumping.

The Way We Stand: A Sequential Case Study on Foot Angle

This study quantifies the significance of foot angle as it relates to common biometric data to assess its use in the clinical realm. There are two objectives to this study;first to determine the relationship foot angle has with ten surveyed biometric data points (age, weight, height, biological makeup, shoe size, orthotic use, physical activity level, competitive sports history, lower extremity injury history, and reason for visiting doctor), and second to determine the average left and right foot angles of the population studied. The duration of this sequential case study with a sample size of 73 was December 9, 2021, to April 7, 2022. Participants were fully informed of the measurement steps, the purpose of the survey, and the goal of the project. Participants were asked to walk down the hallway as a distraction to collect the most accurate data on the participants’ stance. This study was performed at the Arizona Institute of Motion, a clinical office and private practice. Participants had the option to decline participation in the study. Correlational calculations and linear regressions were performed to support or reject the existence of a relationship between foot angle and the biometric data. It was found that the average left foot angle was 26.35 degrees, and the average right foot angle was 26.54 degrees. It was found that there was a strong positive correlation between left and right foot angles, and a weak positive relationship with both foot angles and weight, height, and shoe size. The optimized linear regression model had an adjusted r2 value of 0.549 for left foot angle against right foot angle, shoe size, and height, and an adjusted r2 value of 0.522 for right foot angle against left foot angle, shoe size, and height. Foot angle had no other relationships with the other biometric data and had limited quantitative significance. Additional study is required to confirm its numerical importance, but foot angle may continue to be used in clinical settings in conjunction with gait analysis and qualitative assessments for musculoskeletal function. Foot angle has limited quantitative significance but may maintain a high potential for clinical utility when used in conjunction with gait analysis and qualitative assessments.

Advances in the efficacy and safety of nano-silver dressings for diabetic foot ulcers(DFU)healing

As a new antimicrobial material,nano-silver dressing has been widely used in the treatment of diabetic foot ulcer(DFU)wounds in recent years.It not only has achieved a satisfactory effect in promoting the healing of DFU,but also has the advantages in controlling wound infection,relieving pain and reducing the frequency of dressing change.In this review,the principle,efficacy and safety of DFU wound healing were reviewed,and the future research directions were prospected.