Efficacy of Negative Pressure Wound Therapy Versus Conventional Moist Dressings on Diabetic Foot Ulcer Healing Trajectories

Overview

Background: Diabetic foot ulcers (DFUs) are severe, chronic complications of diabetes carrying a high risk of amputation. While Negative Pressure Wound Therapy (NPWT) is an active biophysical treatment, clinical evidence using multidimensional tools in Middle Eastern settings like Jordan has been limited. Methods: A 3-month randomized controlled trial (January-May 2026) was conducted at the National Center for Diabetes, Endocrinology, and Genetics (NCDEG) in Amman, Jordan, involving 60 patients with chronic DFUs. Participants were randomized to either an intervention group receiving NPWT (80-125 mmHg, changed every 4 days) or a control group receiving conventional moist dressings (changed every 2 days). Wound trajectories were assessed using the 13-item Bates-Jensen Wound Assessment Tool (BWAT©).

Introduction Diabetic foot ulcers (DFUs) represent one of the most debilitating, complex, and costly microvascular and macrovascular complications of diabetes mellitus (DM), imposing profound clinical, economic, and psychosocial burdens on patients and healthcare systems globally. Globally, an estimated 15% to 25% of individuals with diabetes will develop a DFU during their lifetime, with up to 20% of these cases progressing to lower-extremity amputations accounting for over 80% of non-traumatic amputations worldwide (Theodorakopoulos \& Armstrong, 2025; Villalba-Aguilar et al., 2025). Pathophysiologically, DFUs result from a synergistic triad of peripheral neuropathy, peripheral arterial disease, and chronic hyperglycemia-induced microvascular dysfunction, compounded by impaired immune surveillance and dysregulated inflammatory signaling (Yang et al., 2021; Zeng et al., 2025). In Jordan, the prevalence of DM among adults has reached approximately 23.7%, reflecting a steep upward trajectory over time. Epidemiologic studies and comprehensive reviews indicate that between 4.6% and 5.3% of diabetic patients in Jordan suffer from active foot ulcers, while an additional 17.2% are categorized as having feet at high risk for ulceration (AlAyed et al., 2017; Mairghani et al., 2017). This growing burden is compounded by systemic healthcare challenges, including restricted primary care access, a scarcity of specialized wound care facilities outside major urban hubs such as Amman and Irbid, and socioeconomic barriers to proper offloading adherence and glycemic self-management factors that collectively lead to delayed presentation, elevated infection rates, and prolonged healing trajectories (Abirami et al., 2024; Dharaneesh et al., 2025). Within this clinical setting, local wound bed management remains a critical therapeutic frontier. Conventional moist wound dressings have long served as the baseline standard of care due to their wide availability, low direct cost, and ease of application (Nirupam \& Vinayak, 2022; Ravisankar et al., 2022). However, conservative modalities often fail to resolve the core pathophysiological derangements of chronic DFUs such as persistent bacterial biofilm colonization, excessive proteolytic matrix metalloproteinase activity, interstitial edema leading to localized tissue hypoxia, and stagnant granulation bed development (Xin et al., 2024; Zeng et al., 2025). Clinically, these shortcomings manifest as prolonged healing times, frequent dressing changes (typically required every 24-48 hours), elevated infection risks, and recurrent hospital readmissions (Sharaf et al., 2025; Sheen et al., 2021). In contrast, Negative Pressure Wound Therapy (NPWT), delivered via Vacuum-Assisted Closure (VAC) systems, represents an active, biophysical modality grounded in mechanical tissue stimulation rather than passive coverage (Rodríguez Angulo et al., 2025). NPWT exerts its therapeutic effects through four interdependent physiological mechanisms: Macrodeformation: Direct mechanical contraction that approximates wound margins; Microdeformation: Cellular-level mechanotransduction that stimulates fibroblast proliferation, endothelial cell migration, and collagen matrix deposition; Exudate Evacuation: Continuous clearance of excess fluid, inflammatory cytokines, proteases, and bacterial loads; and Perfusion Modulation: Reduction of interstitial edema and restoration of microvascular blood flow (Saramago et al., 2025; Xin et al., 2024; Zeng et al., 2025). Recent syntheses of global data including meta-analyses covering over 1,900 patients across 23 studies confirm that NPWT significantly reduces time to complete wound closure and increases the probability of full epithelialization at 12 weeks compared to conventional dressings (Villalba-Aguilar et al., 2025; Yang et al., 2024). Despite robust international evidence supporting NPWT in high-income settings, the translational validity, feasibility, and practical implementation of NPWT within Middle Eastern and resource-constrained developing healthcare environments like Jordan remain insufficiently explored. Specifically, there is a lack of rigorous experimental studies evaluating NPWT within national healthcare infrastructures governed by the Ministry of Health and the Royal Medical Services, particularly regarding patient adherence, device feasibility, and interaction with patient-specific covariates (e.g., age, gender, employment, and baseline glycemic control, HbA1c). To address these knowledge gaps, a Randomized Controlled Trial (RCT) was conducted to evaluate the comparative clinical efficacy and synergistic potential of Negative Pressure Wound Therapy (NPWT) versus conventional moist dressings on wound healing outcomes among diabetic foot ulcer patients in Jordan. By assessing the biophysical impacts of NPWT across 13 distinct anatomical and physiological subdomains measured using the Bates-Jensen Wound Assessment Tool (BWAT©) alongside Jordan-specific clinical and social determinants, this research provides contextualized empirical evidence to support the National Diabetes Strategy and advance sustainable DFU management. Alternative Hypothesis (H1): Patients with diabetic foot ulcers receiving Negative Pressure Wound Therapy (NPWT) in a randomized controlled trial will exhibit statistically significant improvements in wound healing parameters evidenced by accelerated healthy granulation tissue formation, enhanced epithelial cell migration/proliferation, greater percentage reductions in wound surface area, diminished exudate/necrotic burden, and lower post-intervention BWAT scores compared to control patients receiving conventional wound dressings. Null Hypothesis (H0): There will be no statistically significant difference in wound healing outcomes or BWAT scores (including granulation tissue formation, epithelialization, percentage reduction in wound surface area, and overall healing rate) between diabetic foot ulcer patients treated with NPWT and those receiving conventional dressings. Previous literature indicates that NPWT (also known as vacuum-assisted closure (VAC)) significantly enhances tissue development and local blood flow, accelerates granulation, decreases wound size, and reduces length of hospital stay while maintaining comparable infection rates (Villalba-Aguilar et al., 2025; Yang et al., 2024). Materials and Methods 1. Research Design This study was designed as a randomized controlled trial (RCT) with a parallel-group, pretest-posttest comparative design. The objective of this study was to evaluate the safety and efficacy of vacuum sealing drainage (VSD) / negative pressure wound therapy (NPWT) versus conventional wound dressing techniques in patients presenting with chronic diabetic foot ulcers (DFUs). Previous literature indicates that NPWT (also known as vacuum-assisted closure (VAC)) significantly enhances tissue development and local blood flow, accelerates granulation, decreases wound size, and reduces length of hospital stay while maintaining comparable infection rates. 2. Setting This study was conducted at the National Center for Diabetes, Endocrinology, and Genetics (NCDEG), a tertiary referral center located in Amman, Jordan. Jordan is a lower-middle-income country covering an area of approximately 89,300 km2, with arable land accounting for only 7.8% of its total surface. The total population is approximately 9.8 million, with 90.3% residing in urban regions. Additionally, Jordan hosts a substantial refugee population, including approximately 629,245 registered Syrian refugees. Over the past two decades, Jordan's healthcare system has advanced significantly, becoming one of the leading healthcare models in the Middle East. The system operates within a comprehensive framework comprising three primary sectors: public, private, and non-profit organizations. Overall, health insurance coverage extends to more than 70% of the Jordanian population. As a national specialized tertiary referral center, the NCDEG manages complex diabetes mellitus (DM) cases across the country, primarily serving a catchment population of 4.1 million residents in Amman. In 2017 alone, the center delivered outpatient clinical services to 116,226 patients, including both insured and non-insured individuals. Standard care at the NCDEG involves routine follow-up visits every three months, during which vital and anthropometric parameters such as height, weight, and blood pressure are measured, alongside regular fundoscopic exams, diabetic foot evaluations, and glycated hemoglobin (HbA1c) assessments. Furthermore, annual screenings for lipid profiles and microvascular complications are conducted as standard clinical practice for all DM patients at the center. For the current study, data collection was carried out from January 2026 May 2026. The clinical setting provided standardized wound assessment, surgical debridement, and follow-up care for all enrolled participants. 3. Participants and Eligibility Criteria 3.1 Inclusion Criteria Aged 18 years or older. Diagnosed with superficial chronic diabetic foot ulcers (partial- or full-thickness) located on the plantar surface, metatarsal heads, or sole (Grade 1/clean ulcers). Had a wound length ranging from 10 to 15 cm. Had controlled diabetes mellitus with stable comorbid conditions (e.g., hypertension or non-end-stage renal disease). Were able to speak and read Arabic. Were able to perform activities of daily living (ADLs) independently. Provided voluntary written informed consent to participate in the study. 3.2 Exclusion Criteria Underlying osteomyelitis, Charcot's joint/arthropathy, or DFUs classified as Wagner Grade 3, 4, or 5. Severe peripheral vascular/arterial diseases, venous insufficiency, or bilateral involvement of both feet. Coagulopathic conditions, active bleeding tendencies, or severe immunocompromising diseases. Cognitive or mental impairments preventing informed participation. Severe diabetic complications (e.g., acute cerebrovascular disease). Pregnancy, active fever, or acutely infected wounds at baseline. 4. Sample Size and Sampling Technique 4.1 Sample Size Determination The sample size was determined based on statistical power calculations targeting an 80% power level and a significance threshold of p \< 0.05, derived from expected differences in wound reduction rates reported in prior literature. Accounting for an anticipated dropout rate of approximately 10%, a total of 60 eligible patients were enrolled and randomly allocated into two equal groups (n = 30 per group: Intervention Group \[VAC\] and Control Group \[Conventional Dressing\]). All 60 participants completed the 3-month trial and were included in the final comparative statistical analysis (N = 60). 4.2 Sampling Technique A simple random sampling technique (lottery method) was utilized to select participants and minimize selection bias. Diabetic patients attending the outpatient clinics from Sunday to Thursday were screened daily for eligibility. Medical registration numbers of eligible patients were drawn randomly without replacement until the target intake (approximately six patients per day) was reached. 5. Randomization, Allocation, and Blinding 5.1 Randomization and Allocation Concealment Following baseline screening, participants were randomly assigned to either Group A (Intervention/VAC) or Group B (Control/Standard Dressing) using a computer-generated randomization sequence. Allocation concealment was strictly maintained using sequentially numbered, sealed, opaque envelopes prepared by an independent researcher who was not involved in participant recruitment or treatment procedures. 5.2 Blinding Due to the physical nature of the dressing applications, blinding of participants and treating clinicians was not feasible. However, outcome assessors responsible for wound measurements and data extraction were blinded to group assignments to reduce evaluation bias. 6. Interventions 6.1 Group A: Vacuum-Assisted Closure (VAC / NPWT) Following initial surgical debridement in the operating room, a sterile foam dressing was applied to the wound bed under aseptic conditions and secured with an adhesive drape to establish an airtight seal. An evacuation tube embedded within the foam was connected to a vacuum unit, delivering continuous sub-atmospheric negative pressure ranging between 80 and 125 mmHg for 96 hours. Exudate was continuously collected into a sealed canister, transforming open ulcerations into controlled, closed, moist healing environments. Dressings were routinely changed under sterile conditions every 4 days during the inpatient stay. 6.2 Group B: Conventional Dressing Patients assigned to the control group received conventional wound dressings applied under standard aseptic protocols on an alternate-day schedule (every 2 days) during their hospital stay. 7. Outcome Measures and Study Instruments 7.1 Study Instruments Data were gathered using a structured two-part research instrument: Part (1): Socio-demographic and Clinical Data Sheet: Evaluated patient age, employment status, treatment modality, baseline HbA1c levels, and relevant medical histories extracted from electronic medical records. Part(2): The Bates-Jensen Wound Assessment Tool (BWAT©): Formerly known as the Pressure Sore Status Tool (PSST©), the BWAT provides objective, numerical scoring for wound tissue characteristics. It demonstrates high validity and inter-rater reliability (correlation coefficients ranging from 0.80 to 0.90) (Mohammed et al., 2022; El-den et al., 2021; and Hassan et al., 2018). The instrument was completed at baseline, at least weekly during the treatment period, and upon final wound closure or study completion. 7.2 Outcome Measures Primary Outcomes: Percentage reduction in wound surface area (cm2) and rate of wound healing over time. Secondary Outcomes: Rate of granulation tissue formation, length of hospital stay (days), incidence of wound infection, and recorded adverse events. 8. Data Collection Procedure and Follow-up After obtaining ethical approvals from the Ministry of Health and institutional clearances from clinic directors, the primary researcher and five trained research assistants (holding Bachelor's degrees in Nursing) conducted daily hospital visits. Research assistants were trained on standard administration of the questionnaire, BWAT scoring, and clinical chart extraction using a standardized checklist. Wound tracings, digital photographs, and microbiological culture swabs were taken at baseline and every 4 days during the initial two weeks. Specific clinical parameters (culture sensitivity, wound dimensions, and granulation percentage) were benchmarked on Day 8. Treatments were continued until complete spontaneous or surgical wound closure, or up to an 8-week endpoint. Discharged patients were followed up monthly via the surgical outpatient department (OPD). Treatment success was defined as complete wound closure within 8 weeks, whereas failure was defined as the inability to achieve closure within this timeframe. 9. Statistical Analysis Data analysis was performed using IBM SPSS Statistics for Windows, Version 25.0. Data screening was conducted to check for missing values, outliers, and normality assumptions. Descriptive statistics: Categorical variables (gender, working status, treatment modality, HbA1c control category) were summarized using frequencies (n) and percentages (%). Continuous variables (age, HbA1c %, BWAT scores) were presented as mean± standard deviation (mean ± SD). Inferential statistics: Paired-samples t-tests were performed to evaluate pre- and post-intervention changes in total and itemized BWAT scores within each group. Independent-samples t-tests were conducted to evaluate direct differences between the intervention group (NPWT, n = 30) and the control group (Conventional Dressing, n = 30) at post-intervention to test the study hypotheses. Pearson's correlation coefficient (r) was utilized to analyze relationships between demographic variables, clinical parameters (HbA1c), and baseline/post-intervention BWAT scores. Parametric assumptions: Normality of distribution was checked for scale variables, homogeneity of variance was tested using Levene's test for independent groups, and linearity assumptions were verified. The level of statistical significance was established at p \< 0.05, with high significance at p \< 0.001. 10. Ethical Considerations The study protocol was approved by the Institutional Review Board (IRB) at the NCDEG (No:………….). Additionally, the trial was officially registered in a public clinical trials registry (ClinicalTrials.gov / Pan African Clinical Trials Registry) (No:………….). Eligible patients received detailed verbal and written explanations regarding the study objectives, procedures, and potential benefits. Participation was entirely voluntary, with explicit guarantees that withdrawal at any stage would not affect standard clinical care. Signed informed consent was obtained prior to data collection. To maintain strict participant confidentiality, all instruments were coded with unique identifiers. Hard copies were secured in locked storage, and electronic data files were encrypted and password-protected, accessible solely by the primary research team. Discussion Diabetic foot ulcers (DFUs) represent one of the most debilitating and costly microvascular and macrovascular complications of diabetes mellitus (DM), imposing a profound clinical, socioeconomic, and psychological burden on affected individuals and healthcare systems globally. Internationally, an estimated 15% to 25% of individuals with diabetes will develop a DFU during their lifetime, with up to 20% of these cases progressing to lower-extremity amputations, accounting for over 80% of non-traumatic amputations worldwide (Theodorakopoulos \& Armstrong, 2025; Villalba-Aguilar et al., 2025). Pathophysiologically, DFUs are rooted in a complex triad of peripheral neuropathy, peripheral arterial disease, and chronic hyperglycemia-induced microvascular dysfunction, which collectively impair immune surveillance, blunt tissue perfusion, and dysregulate inflammatory signaling (Yang et al., 2021; Zeng et al., 2025). In Jordan, where adult diabetes prevalence has escalated to approximately 23.7%, foot complications pose a critical public health challenge. National epidemiologic data indicate that 5.3% of Jordanian diabetic patients present with active foot ulcers, while an additional 17.2% are categorized as having feet at high risk for ulceration (AlAyed et al., 2017; Mairghani et al., 2017). This growing burden is further compounded by institutional barriers, including limited primary care specialized wound services outside major urban centers like Amman, as well as patient-level socioeconomic constraints regarding offloading adherence and glycemic self-management (Dharaneesh et al., 2025; Sakthi Abirami et al., 2024). In this clinical landscape, conventional moist wound dressings have long remained the standard of care due to their low cost and simplicity (Nirupam \& Vinayak, 2022; Ravisankar et al., 2022). However, passive dressings often fail to address the core pathophysiologic derangements of chronic DFUs such as persistent bacterial biofilms, elevated matrix metalloproteinases, edema-induced tissue hypoxia, and stagnant granulation (Xin et al., 2024; Zeng et al., 2025). To address these limitations, Negative Pressure Wound Therapy (NPWT), or Vacuum-Assisted Closure (VAC), has emerged as an active, biophysical modality. NPWT promotes wound closure via macrodeformation (wound margin approximation), microdeformation (mechanotransduction-stimulated fibroblast proliferation and collagen synthesis), continuous exudate/cytokine evacuation, and perfusion modulation through interstitial edema reduction (Rodríguez Angulo et al., 2025; Saramago et al., 2025). Despite international randomized evidence supporting NPWT, empirical data regarding its clinical efficacy within resource-constrained Middle Eastern settings like Jordan have remained scarce. This study addressed this gap by evaluating the therapeutic impact of NPWT on wound healing trajectories using the Bates-Jensen Wound Assessment Tool (BWAT©) among Jordanian DFU patients. Clinical Efficacy of NPWT on Wound Healing Parameters The empirical findings of this study offer robust quantitative support for the superior therapeutic efficacy of NPWT over conventional management. Before the intervention, participants in both trial groups exhibited severe baseline wound impairment (NPWT mean BWAT: 36.43 ± 8.40; Control mean BWAT: 36.10 ± 8.12). Following the 3-month intervention, total BWAT scores in the NPWT group demonstrated a dramatic and statistically significant reduction to 19.06 ± 3.22 (t = 10.38, p \< 0.001). Crucially, direct comparative analysis using independent-samples t-tests demonstrated that post-intervention BWAT scores were significantly lower in the NPWT group compared to the control group (19.06 ± 3.22 vs. 28.45 ± 4.15; t = -9.720, p \< 0.001). This confirms the superiority of active biophysical NPWT over passive moist dressings, directly confirming Alternative Hypothesis (H1). Detailed analysis of individual BWAT subdomains revealed uniform, highly significant improvements (p \< 0.001) across all 13 clinical parameters favoring NPWT over control dressings. The most pronounced therapeutic effects were observed in exudate amount (t = 8.80), peripheral tissue induration (t = 9.79), exudate type (t = 7.99), and necrotic tissue amount (t = 7.49). These physiological shifts directly reflect the biophysical actions of continuous negative pressure (-80 to -125 mmHg). By actively removing proteinaceous exudate and inflammatory mediators, NPWT resolves peri-wound induration and tissue edema, thereby reversing localized hypoxia and facilitating rapid enzymatic/autolytic debridement of necrotic slough (Sheen et al., 2021; Sharaf et al., 2025). Furthermore, structural wound bed parameters including wound size (t = 5.52), depth (t = 5.99), granulation tissue formation (t = 6.14), and epithelialization (t = 6.12) exhibited substantial acceleration. These clinical improvements align with the mechanotransduction principles described by Zeng et al. (2025), wherein micro-mechanical stretch forces stimulate endothelial cell migration, microvascular sprout formation, and robust deposition of extracellular matrix. Interrelationships between Demographic, Clinical Variables, and Healing Trajectories The bivariate Pearson correlation analysis (r) elucidated crucial interactions between patient baseline demographics, systemic metabolic control, and localized wound healing outcomes. A central finding of this study is the significant positive correlation between age and post-intervention total BWAT scores (r = 0.39, p = 0.040). This indicates that older participants tended to retain higher post-treatment BWAT scores (reflecting slower wound closure rates). Aging is physiologically accompanied by cellular senescence, reduced capillary density, blunted fibroblast responsiveness, and impaired collagen cross-linking, which collectively delay biophysical tissue repair (Theodorakopoulos \& Armstrong, 2025). Additionally, age showed a strong inverse correlation with modality of treatment (r = -0.36, p = 0.05) and a positive correlation with baseline HbA1c levels (r = 0.40, p = 0.02), highlighting how older retired patients in Jordan often face cumulative metabolic and physical vulnerabilities. Gender demonstrated notable associations with both clinical severity and healing capacity. Females represented 50% of the study cohort and exhibited higher baseline wound severity (r = 0.45, p = 0.010). However, gender demonstrated significant negative correlations with both post-intervention HbA1c (r = -0.40, p = 0.05) and post-intervention BWAT scores (r = -0.40, p = 0.05). This suggests that female participants achieved a greater relative magnitude of wound repair and metabolic optimization over the 3-month trial. This trend may be attributed to higher adherence to home-based dressing care, offloading instructions, and dietary management among female patients in domestic settings within Jordanian social structures (AlAyed et al., 2017). Regarding employment status, employed participants demonstrated lower baseline wound severity (r = -0.36, p = 0.050), but displayed a slight positive correlation with post-intervention BWAT scores (r = 0.37, p = 0.040). Active employment often demands prolonged standing or weight-bearing, which creates mechanical shear stress and hinders optimal offloading, a critical prerequisite for uninhibited NPWT action (Dharaneesh et al., 2025). Systemic glycemic control remains a primary determinant of DFU resolution. In our sample, 75% of participants presented with uncontrolled baseline diabetes (HbA1c ≥7 %), with an overall mean of 7.87 ± 1.39. Interestingly, baseline BWAT scores were inversely correlated with post-intervention HbA1c (r = -0.46, p = 0.010), reflecting that patients presenting with the most severe baseline wounds received more intensive multidisciplinary clinical oversight, leading to secondary improvements in glycemic management. However, post-intervention HbA1c was not significantly correlated with final BWAT scores (r = 0.21, p = 0.270). This finding underscores that while systemic glycemic regulation is vital for long-term recurrence prevention, localized active biophysical mechanical stimulation (via NPWT) can successfully drive granulation and tissue closure even in the presence of moderate metabolic derangement (Villalba-Aguilar et al., 2025; Xin et al., 2024). Strengths, Limitations, and Future Directions This study provides crucial empirical evidence establishing the clinical viability and therapeutic superiority of NPWT within the Jordanian healthcare context. By utilizing a standardized, validated tool (BWAT©), the study objectively quantified 13 distinct anatomical and physiological dimensions of wound repair. However, certain limitations must be acknowledged. First, the sample size (N = 60; n = 30 per group) from a single specialized tertiary center (NCDEG in Amman) may limit the generalizability of the findings to rural primary care health centers across Jordan. Second, while the 3-month follow-up period effectively captured rapid wound reduction and granulation, long-term outcomes such as complete 12-month ulcer recurrence rates and secondary amputation incidence were not tracked. Third, economic parameters (such as direct equipment costs versus indirect nursing care hours saved) were not formally measured in a cost-effectiveness model. Conclusion and Practice Recommendations In conclusion, the integration of Negative Pressure Wound Therapy significantly accelerates DFU healing trajectories compared to conventional dressing modalities among Jordanian patients. The study hypothesis (H1) was supported by demonstrating statistically significant superior post-intervention BWAT scores in the NPWT group compared to the control group (p \< 0.001). NPWT effectively resolves local edema, reduces exudate burden, clears necrotic tissue, and promotes healthy granulation bed preparation. Based on these findings, institutional policy at major healthcare sectors, including the Ministry of Health and Royal Medical Services, should prioritize the incorporation of NPWT protocols into standardized diabetic foot management pathways. Future multi-center randomized controlled trials incorporating cost-effectiveness evaluations and long-term recurrence tracking are recommended to guide national health policy in Jordan.