Diabetes mellitus (DM) is a metabolic disorder marked by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both. It is associated with long-term damage, dysfunction, and failure of various organs such as the eyes, kidneys, nerves, heart, and blood vessels[1]. Among the myriad complications of diabetes, diabetic foot ulcers (DFUs) remain one of the most debilitating and costly, significantly impacting patients’ quality of life and health systems worldwide. Foot infections and ulcers are frequent complications in diabetic patients and account for nearly 20% of diabetes-related hospital admissions. The lifetime risk of developing a diabetic foot ulcer among individuals with diabetes is estimated between 15% to 25%[2]. Peripheral neuropathy, peripheral arterial disease, and infection are primary factors that contribute to ulcer development and impede healing. The complex interplay between these factors leads to the formation of ulcers that are often chronic, refractory to treatment, and prone to infection, which in turn increases the risk of amputations. Approximately 85% of diabetic lower extremity amputations are preceded by foot ulcers, underscoring the critical importance of effective ulcer management[3]. Traditional wound care in DFUs involves debridement, infection control, pressure offloading, and dressings. Conventional dressings, such as saline or povidone-iodine (PI) based dressings, primarily serve to protect the wound and maintain a moist environment but often lack active antimicrobial properties and do not promote accelerated healing or tissue regeneration. Furthermore, these dressings require frequent changes, which can be painful and disruptive to the healing tissue. The emergence of antibiotic-resistant pathogens has further complicated the management of infected DFUs, necessitating alternative therapeutic approaches[4]. Silver, a metal with well-known antimicrobial properties, has been used in wound care for centuries. Silver nanoparticles (AgNPs), which are silver particles ranging from 1 to 100 nanometers in size, possess unique physicochemical properties due to their small size and large surface area. These properties enable AgNPs to exert strong broad-spectrum antimicrobial effects, including against multidrug-resistant bacteria. Unlike traditional antibiotics, AgNPs operate through multiple mechanisms, such as disrupting bacterial cell membranes, generating reactive oxygen species, and interfering with DNA and protein functions, reducing the likelihood of resistance development [5]. In addition to their antimicrobial actions, AgNPs have demonstrated potential in promoting wound healing by modulating inflammation, stimulating granulation tissue formation, promoting angiogenesis, and enhancing collagen synthesis. This multifaceted effect makes AgNPs particularly promising for chronic wounds such as diabetic foot ulcers, where persistent infection and impaired tissue regeneration are major challenges[6]. Aim To evaluate and compare the efficacy of silver nanoparticles dressing versus conventional povidone-iodine dressing in the healing of diabetic foot ulcers. Objectives 1. To assess the rate of reduction in wound surface area and volume during the follow-up period. 2. To evaluate the time taken for the appearance of granulation tissue and reduction of slough. 3. To compare the overall healing outcomes and duration of hospital stay between the two dressing methods.

Source of Data: The study was conducted on diabetic foot ulcer patients attending the Department of Surgery, SSG Hospital and Medical College, Vadodara. Patients fulfilling the inclusion criteria and consenting to participate were enrolled. Study Design: This was a prospective, single-center, single-blinded randomized controlled trial comparing silver nanoparticles dressing (study group) and conventional povidone-iodine dressing (control group). Study Location: Department of Surgery, SSG Hospital and Medical College, Vadodara. Study Duration: The study was conducted over a period of one year following approval from the Scientific Review Committee (SRC). Sample Size: A total of 100 patients with diabetic foot ulcers were recruited and randomized into two groups of 50 each. Inclusion Criteria: • Patients of either sex with Type 1 or Type 2 diabetes mellitus on oral hypoglycemics or insulin. • Presence of diabetic foot ulcer for at least 6 weeks duration. • Ulcer surface area between 2 to 10 cm². • Wagner grade I or II ulcers (superficial or involving tendon without gangrene). • Both infected and non-infected ulcers. • Patients able and willing to provide informed consent. Exclusion Criteria: • Wagner grade III or higher ulcers, gangrene or peripheral arterial disease. • Suspected osteomyelitis. • Ulcers smaller than 2 cm² or larger than 10 cm². • Patients with hypersensitivity to silver. • Patients with serum albumin <3 g/dl, renal dialysis, immunocompromised states, or recent chemotherapy/radiotherapy. • Those refusing consent. Procedure and Methodology: After obtaining informed consent, patients were randomly allocated to receive either silver nanoparticles dressing or conventional povidone-iodine dressing using an envelope method. Both groups received standard wound care including debridement as needed and offloading of pressure on the ulcer site. Dressings were changed at scheduled intervals weekly, with close monitoring of wound parameters such as surface area, volume, presence of granulation tissue, and slough. Wound measurements were calculated using Mayrovitz formula for surface area (Length × Width × 0.785) and Kundin formula for volume (Area × Depth × 0.327). Patients were followed weekly for up to 12 weeks or until complete healing, whichever was earlier. Data on ulcer progression, infection status, and complications were collected systematically. Sample Processing: Swabs or tissue cultures were taken from ulcers at baseline and during follow-up visits to identify microbial colonization and guide antibiotic therapy. Statistical Methods: Data were analyzed using appropriate statistical tests to compare healing rates, wound size reduction, and time to granulation between groups. Continuous variables were expressed as means ± SD and compared using t-tests or non-parametric equivalents. Categorical variables were compared using chi-square tests. A p-value <0.05 was considered statistically significant. Data Collection: All patient data, including demographics, clinical parameters, ulcer measurements, and treatment outcomes, were recorded on standardized case report forms and maintained confidentially.

Table 1: Baseline Demographic and Clinical Characteristics (N=100) Variable Silver Nanoparticles (n=50) Conventional Dressing (n=50) Test of Significance (t/χ²) 95% Confidence Interval P value Age (years), Mean ± SD 56.3 ± 10.7 57.8 ± 11.2 t = 0.67 -4.1 to 7.4 0.50 Male, n (%) 34 (68%) 33 (66%) χ² = 0.04 - 0.84 Duration of Diabetes (years), Mean ± SD 9.8 ± 4.2 10.3 ± 5.1 t = 0.62 -2.7 to 3.7 0.54 Wagner Grade I Ulcers, n (%) 31 (62%) 33 (66%) χ² = 0.17 - 0.68 Wagner Grade II Ulcers, n (%) 19 (38%) 17 (34%) Ulcer Surface Area (cm²), Mean ± SD 6.2 ± 2.1 6.1 ± 2.0 t = 0.21 -0.9 to 1.1 0.83 Ulcer Volume (cm³), Mean ± SD 3.8 ± 1.4 3.9 ± 1.6 t = 0.25 -0.7 to 0.9 0.80 Note: No statistically significant differences observed at baseline, confirming homogeneity between groups. The baseline demographic and clinical characteristics of the study participants showed no statistically significant differences between the two groups, confirming their comparability at the start of the trial. The mean age of patients treated with silver nanoparticles dressing was 56.3 ± 10.7 years, while it was 57.8 ± 11.2 years in the conventional dressing group (p = 0.50). The gender distribution was also similar, with males comprising 68% and 66% of the silver nanoparticles and conventional dressing groups respectively (p = 0.84). The duration of diabetes was comparable between groups, averaging 9.8 ± 4.2 years versus 10.3 ± 5.1 years (p = 0.54). Furthermore, ulcer characteristics such as Wagner grading showed no significant difference, with Grade I ulcers observed in 62% of the silver nanoparticle group and 66% of the control group (p = 0.68). Ulcer surface area and volume were closely matched as well, with mean values of 6.2 ± 2.1 cm² versus 6.1 ± 2.0 cm² (p = 0.83) and 3.8 ± 1.4 cm³ versus 3.9 ± 1.6 cm³ (p = 0.80) respectively. Table 2: Rate of Reduction in Wound Surface Area and Volume over 12 Weeks Parameter Silver Nanoparticles (Mean ± SD) Conventional Dressing (Mean ± SD) Test of Significance (t) 95% CI for Difference P value % Reduction in Surface Area 78.3% ± 8.9 62.5% ± 10.4 t = 8.73 12.5% to 20.7% <0.001 % Reduction in Volume 74.9% ± 9.2 59.1% ± 11.1 t = 8.14 11.3% to 19.6% <0.001 Over the 12-week follow-up period, the silver nanoparticles dressing group demonstrated a significantly greater reduction in wound surface area and volume compared to the conventional dressing group. Specifically, the percentage reduction in surface area was 78.3% ± 8.9% in the silver nanoparticle group compared to 62.5% ± 10.4% in the conventional group (p < 0.001), with a 95% confidence interval for the difference between 12.5% to 20.7%. Similarly, volume reduction was significantly higher in the silver nanoparticle group at 74.9% ± 9.2%, versus 59.1% ± 11.1% in the control group (p < 0.001), with a confidence interval of 11.3% to 19.6%. Table 3: Time Taken for Appearance of Granulation Tissue and Reduction of Slough Parameter Silver Nanoparticles (Mean ± SD, weeks) Conventional Dressing (Mean ± SD, weeks) Test of Significance (t) 95% CI for Difference P value Time to Appearance of Granulation Tissue 2.8 ± 0.9 4.5 ± 1.2 t = 7.64 -2.3 to -1.2 weeks <0.001 Time to Complete Slough Reduction 4.2 ± 1.1 6.0 ± 1.4 t = 7.24 -2.2 to -1.0 weeks <0.001 The healing process was also faster in patients treated with silver nanoparticles. The time taken for the appearance of granulation tissue was significantly shorter in this group, occurring at 2.8 ± 0.9 weeks compared to 4.5 ± 1.2 weeks in the conventional dressing group (p < 0.001). Likewise, the time to complete reduction of slough was faster in the silver nanoparticle group, averaging 4.2 ± 1.1 weeks versus 6.0 ± 1.4 weeks in the control group (p < 0.001). Table 4: Overall Healing Outcomes and Duration of Hospital Stay Parameter Silver Nanoparticles (Mean ± SD / n%) Conventional Dressing (Mean ± SD / n%) Test of Significance (t/χ²) 95% CI for Difference P value Complete Healing at 12 weeks, n (%) 37 (74%) 25 (50%) χ² = 7.40 - 0.006 Mean Duration of Hospital Stay (days) 14.8 ± 4.3 19.6 ± 5.1 t = 5.27 -6.8 to -3.2 days <0.001 Presence of Discharge at 12 weeks, n (%) 8 (16%) 18 (36%) χ² = 5.08 - 0.024 Overall healing outcomes favored the silver nanoparticles dressing. At the end of 12 weeks, 74% of ulcers in the silver nanoparticle group achieved complete healing compared to 50% in the conventional group (p = 0.006). This accelerated healing was accompanied by a significantly shorter mean hospital stay of 14.8 ± 4.3 days versus 19.6 ± 5.1 days for the control group (p < 0.001). Additionally, the presence of discharge at 12 weeks was significantly lower in the silver nanoparticle group (16%) compared to the conventional dressing group (36%) (p = 0.024), indicating better wound resolution.

The baseline demographic and clinical characteristics (Table 1) showed no significant differences between the silver nanoparticles (AgNPs) group and the conventional dressing group, confirming that both groups were well matched at the start of the study. This homogeneity is critical to ensure that any differences observed in outcomes are attributable to the intervention rather than baseline disparities. Similar findings regarding comparable baseline characteristics have been reported by Almonaci Hernández CAet al. (2017)[7] and Tajdar Yet al. (2024)[8], who also ensured matched groups in their randomized trials comparing silver-based dressings and conventional treatments for diabetic foot ulcers (DFUs). Table 2 demonstrates a significantly greater reduction in wound surface area and volume in the AgNP group compared to conventional dressing, with p-values <0.001. This indicates a superior efficacy of silver nanoparticles in promoting wound contraction and healing. These results align with findings from Yang Let al. (2021)[9], who reported faster wound size reduction with silver nanoparticle dressings, attributed to their broad-spectrum antimicrobial effects and ability to stimulate tissue regeneration. Moreover, Rybka Met al. (2022)[10] in their systematic review also concluded that silver dressings significantly reduce healing time and exudate in DFUs compared to iodine-based dressings, reinforcing the current study's findings. The time taken for granulation tissue appearance and slough reduction (Table 3) was notably shorter in the silver nanoparticle group. This faster transition to the proliferative phase of healing reflects AgNPs' ability to modulate inflammation and promote fibroblast proliferation, angiogenesis, and collagen synthesis, as detailed by Yahia EAet al. (2021)[11]. Such accelerated granulation tissue formation is crucial in diabetic ulcers, where chronic inflammation often impairs healing. Similar acceleration in granulation tissue appearance has been observed by Jiang Pet al. (2023)[12], highlighting silver nanoparticles' regenerative advantages over conventional agents. The overall healing outcomes and hospital stay duration (Table 4) further emphasize the clinical benefits of AgNP dressings. The higher complete healing rate (74% vs 50%) and shorter hospital stay (mean difference approx. 5 days) with AgNPs reflect improved wound management, reduced infection rates, and quicker recovery. This is consistent with the results of Kalantari Ket al. (2020)[13], who documented reduced healing times and hospitalizations with silver nanoparticle treatment. Furthermore, the reduced presence of discharge at 12 weeks suggests better infection control, an effect corroborated by Zhang Ket al. (2021)[14], who underscored silver nanoparticles' potent antimicrobial activity against multidrug-resistant organisms commonly found in chronic wounds.

The present prospective randomized study demonstrated that silver nanoparticles dressing is significantly more effective than conventional povidone-iodine dressing in the healing of diabetic foot ulcers. Patients treated with silver nanoparticles showed faster wound contraction, earlier appearance of granulation tissue, and quicker slough reduction. The silver nanoparticle group also exhibited higher rates of complete healing within 12 weeks, reduced hospital stay duration, and lower incidence of wound discharge, indicating better infection control and accelerated recovery. These findings underscore the clinical advantages of silver nanoparticle dressings as a promising therapeutic option in the management of diabetic foot ulcers, offering improved outcomes and potential reduction in morbidity associated with chronic wounds.

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