EFFICACY OF LOCAL ANTIBACTERIAL THERAPY USING VANCOMYCIN-IMPREGNATED GELATIN SPONGES IN THE SURGICAL MANAGEMENT OF PERIPROSTHETIC INFECTIONS

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 197 EFFICACY OF LOCAL ANTIBACTERIAL THERAPY USING VANCOMYCIN-IMPREGNATED GELATIN SPONGES IN THE SURGICAL MANAGEMENT OF PERIPROSTHETIC INFECTIONS M.Yu. Karimov1, U.T. Kholmurodov2, J.Sh. Kayumov3 Tashkent State Medical University, Tashkent, Uzbekistan1,2,3 https://doi.org/10.5281/zenodo.17854715 Abstract. Periprosthetic joint infection (PJI) remains one of the most severe and challenging complications after total hip arthroplasty (THA), contributing to higher morbidity rates, extended hospital stays, and increased healthcare expenditures. Conventional management typically involves systemic antimicrobial therapy alongside surgical procedures such as debridement or staged revision. Yet, systemic antibiotics may be unable to achieve adequate concentrations at the infection site, especially in cases complicated by biofilm formation. This study investigates the therapeutic effectiveness of localized antibiotic delivery via bioresorbable gelatin sponges saturated with vancomycin (BGS) for treating PJI. A prospective clinical evaluation included 12 patients diagnosed with PJI—7 presenting with early-onset infection (≤3 months after surgery) and 5 with late-onset infection (>3 months postoperatively). All patients underwent debridement in combination with implantation of vancomycin-loaded BGS for targeted drug release. Infection resolution was observed in 11 of the 12 participants (91.7%). Only one patient experienced delayed wound healing, with no cases of recurrent infection reported. These results indicate that localized antibiotic administration is a safe and effective adjunctive strategy for PJI treatment, offering reduced reinfection rates and minimizing the need for high-dose systemic antibiotics. Keywords: periprosthetic joint infection, total hip arthroplasty, localized antibiotic therapy, bioresorbable gelatin sponges, vancomycin. Introduction Periprosthetic joint infection (PJI) is recognized as one of the most serious and costly complications following total hip arthroplasty (THA). Epidemiological data indicate that this condition develops in approximately 1–2% of primary hip arthroplasty cases and in 5–15% of revision procedures, making it a significant challenge for orthopedic surgeons worldwide [1]. PJI not only increases patient morbidity but also leads to substantial financial burden on healthcare systems due to prolonged hospitalization, repeated surgeries, and long-term antibiotic therapy. Furthermore, the functional decline associated with persistent infection or multiple revisions severely affects the patient’s quality of life [2]. The current treatment paradigm for PJI typically includes a combination of systemic antimicrobial therapy and surgical approaches, which may involve thorough debridement, implant retention strategies, or two-stage revision arthroplasty depending on the severity and chronicity of the infection [3]. Despite their widespread use, systemic antibiotics frequently demonstrate limited effectiveness because they do not consistently achieve therapeutic concentrations within bacterial biofilms that adhere to the prosthetic surfaces. Biofilm formation serves as a protective barrier that SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 198 reduces antibiotic penetration and fosters antimicrobial resistance, often resulting in treatment failure or infection recurrence [4]. Given these limitations, localized antibiotic delivery has emerged as a promising adjunctive therapy. This method allows substantially higher antimicrobial concentrations to be achieved directly at the infection site, while reducing systemic exposure and potentially lowering toxicity risks [5]. Among the available local delivery systems, bioresorbable gelatin sponges (BGS) impregnated with vancomycin represent an innovative and practical solution. These sponges provide immediate and sustained release of the antibiotic into the periprosthetic space. Their biodegradable nature offers a considerable advantage over polymethylmethacrylate (PMMA) antibiotic beads, which must be surgically removed once drug elution is completed. In contrast, gelatin-based carriers naturally degrade in vivo, eliminating the need for an additional surgical procedure and minimizing patient discomfort. In light of these potential benefits, the present study was designed to comprehensively evaluate the clinical efficacy and safety of localized antibiotic therapy using vancomycin-loaded bioresorbable gelatin sponges in patients diagnosed with PJI after THA. The research aimed to assess not only infection eradication rates but also wound healing profiles, complication rates, and the overall feasibility of integrating this method as an adjunct to standard surgical debridement. By analyzing clinical outcomes, this study seeks to determine whether vancomycin-impregnated BGS can enhance infection control, reduce recurrence risk, and improve postoperative recovery in patients with periprosthetic hip joint infections. Materials and methods Study Design and Patient Selection. A prospective observational study was carried out over a two-year period, from January 2023 to December 2024, at a high-volume tertiary orthopedic referral center specializing in hip reconstruction and revision surgery. During the study period, 12 patients who met the diagnostic criteria for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) were consecutively enrolled. Infection Classification Patients were stratified according to the temporal onset of infection following arthroplasty:  Early PJI, defined as infection occurring within ≤3 months postoperatively — 7 patients;  Late PJI, diagnosed after >3 months postoperatively — 5 patients. This classification was used to guide clinical decision-making, as early infections typically respond more favorably to debridement and implant retention, whereas late cases often exhibit mature biofilm formation and higher microbial resistance. Inclusion Criteria Patients were eligible for enrollment if they met all the following conditions:  A confirmed diagnosis of PJI based on the Musculoskeletal Infection Society (MSIS) major and minor criteria  Absence of known hypersensitivity reactions to vancomycin or porcine-derived gelatin  Suitability for surgical intervention as assessed by the anesthesiology and orthopedic teams Exclusion Criteria Patients were excluded if any of the following conditions were present: SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 199 Severe systemic comorbidities (e.g., uncontrolled cardiac, pulmonary, or renal failure) that contraindicated surgery Prior failure of localized antibiotic therapy or previous implantation of antibiotic carriers Active systemic infection unrelated to the prosthesis Preparation of Vancomycin-Impregnated Gelatin Sponges The study utilized bioresorbable medical-grade porcine gelatin sponges, selected due to their long-established record of biocompatibility, biodegradability, and intrinsic hemostatic capabilities. Porcine gelatin is widely used in surgical practice because it exhibits excellent elasticity, rapid fluid absorption, and minimal immunogenicity. These sponges were specifically engineered to serve as an antibiotic carrier system, ensuring controlled and sustained vancomycin release during the early postoperative period when bacterial load is highest. The material was designed to undergo complete bioresorption within approximately two weeks, leaving no residual foreign body. Gelatin Sponge Specifications Dimensions: 80 × 50 × 10 mm Surface area: 160 cm² Manufacturer: Ethicon (Spongostan®), a widely used hemostatic agent Estimated degradation period: ~14 days Primary functional roles: hemostasis, space-filling, and localized antibiotic delivery The structural porosity of the sponge enhances its ability to absorb aqueous antibiotic formulations, making it an optimal biodegradable carrier for local drug delivery in PJI management. Selection and Impregnation of Antibiotics Antibiotic Selection. Vancomycin was chosen as the primary antimicrobial agent because it provides potent coverage against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci, which represent the most common pathogens implicated in PJI. The drug also demonstrates:  strong affinity for biofilm-embedded bacterial cells  stability in local delivery systems  predictable release kinetics in biodegradable matrices These properties render vancomycin an optimal antibiotic for localized treatment strategies in hip PJI. Antibiotic Impregnation Protocol The loading of gelatin sponges with vancomycin was performed using a standardized, quality-controlled three-phase protocol consisting of hydration, drying, and sterilization. This approach ensured uniform drug distribution, optimal retention, and preservation of antimicrobial activity. 1. Hydration of Gelatin Sponges Hydration was conducted using sterile 0.9% physiological saline as a solvent medium. The required fluid volume was calculated based on the sponge’s dimensions and microporous architecture. For a sponge measuring 80×50×10 mm (160 cm² total surface area), a concentration of 2000 mg vancomycin per 100 cm² was selected to achieve high local bactericidal levels. Each sponge was immersed in 15 mL of saline containing 3200 mg of vancomycin. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 200 The hydration period lasted 30 minutes, allowing the antibiotic solution to diffuse thoroughly throughout the gelatin matrix. Gentle compression and release cycles were performed to ensure complete saturation without excess fluid accumulation, preventing unintended early elution. This technique ensured homogeneous loading of vancomycin across the entire sponge volume. 2. Drying Process for Antibiotic Stabilization Following saturation, the sponges underwent a controlled drying stage aimed at immobilizing vancomycin within the gelatin microstructure. Drying was carried out using a Venticell® low-temperature drying chamber. Temperature conditions were maintained at 30–40°C for 45 minutes, preventing thermal denaturation of gelatin fibers and degradation of vancomycin molecules. Low-temperature drying stabilizes the antibiotic, contributes to predictable release kinetics, and preserves sponge morphology. This step was crucial to avoid premature dissolution during handling or surgical implantation. 3. Sterilization of Vancomycin-Loaded Sponges Sterilization was performed using gamma irradiation, a method well-suited for temperature-sensitive biomaterials. The Smart 150 D gamma irradiation system was utilized. Each sterilization cycle lasted 75 minutes, ensuring complete eradication of microbial contaminants. Gamma radiation was preferred over steam autoclaving because high heat may compromise gelatin structure and degrade the antibiotic. Previous research confirms that vancomycin maintains structural and pharmacological stability under gamma irradiation, making it an optimal sterilization method for implantable antimicrobial carriers. This ensured the final product was sterile, structurally intact, and pharmacologically active. Results Clinical Outcomes. Among the 12 patients included in the study, 11 individuals (91.7%) demonstrated a favorable clinical outcome, which was defined as full eradication of infection, absence of postoperative recurrence, and satisfactory restoration of functional activity in the operated hip joint. Improvement in systemic inflammatory markers was evident early in the postoperative period. Specifically, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels showed a steady decline, reaching values within normal physiological limits by the fourth postoperative week. These laboratory improvements strongly correlated with both clinical recovery and normalization of local wound conditions. Table 1 summarizes the longitudinal changes in key inflammatory and hematologic biomarkers at four distinct time points: preoperatively, 1 week, 4 weeks, and 12 weeks after surgery. Across all parameters—including CRP, ESR, and white blood cell (WBC) count—a statistically significant decline was observed (p < 0.001 for CRP and ESR; p < 0.01 for WBC). These reductions confirm the efficacy of localized vancomycin delivery in rapidly controlling infection and suppressing inflammatory activity. Table 1. Dynamics of Laboratory Markers Post-Surgery SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 201 Marker Pre-Op 1 Week 4 Weeks 12 Weeks p-value CRP (mg/L) 96 ± 12 48 ± 8 12 ± 4 5 ± 2 < 0.001 ESR (mm/h) 57 ± 10 40 ± 6 20 ± 5 10 ± 3 < 0.001 WBC (×10⁹/L) 12.5 ± 1.8 9.8 ± 1.2 7.2 ± 0.9 6.5 ± 0.7 < 0.01 CRP: The mean CRP level decreased from 96 mg/L preoperatively to 12 mg/L at week 4, indicating a remarkable suppression of acute inflammation. By week 12, CRP values approached normal physiological ranges. ESR: A two-fold reduction was recorded by week 4, demonstrating substantial improvement in systemic inflammatory response. WBC: Although WBC count was less dramatically elevated preoperatively compared to CRP and ESR, a consistent downward trend was evident, supporting ongoing infection control. Satisfactory Outcome Case One patient (8.3%) exhibited a satisfactory rather than optimal clinical outcome, primarily due to delayed wound healing, which necessitated extended local wound care and short-term adjunctive therapy. Despite this complication, the patient did not demonstrate any microbiological evidence of reinfection, and clinical stabilization was achieved by the end of the third postoperative month. This case highlights the potential influence of individual wound-healing variability, comorbidities, or microbial load on treatment course, despite appropriate surgical and antimicrobial measures. Table 2 compares the outcomes between early-onset and late-onset PJI groups. All 7 patients with early PJI (100%) experienced positive outcomes, reflecting the well-established fact that earlier infections respond more effectively to debridement combined with localized antibiotic therapy, likely due to less mature biofilm formation. In contrast, among patients with late PJI: out of 5 patients (80%) achieved positive outcomes 1 patient (20%) had a satisfactory outcome with delayed wound healing Notably, no reinfections occurred in either group, demonstrating the reliability of localized vancomycin delivery. The statistically significant p-values (0.005 for early PJI and 0.03 for late PJI) indicate a meaningful difference in outcomes between early and late infection groups, supporting the clinical advantage of earlier diagnosis and intervention. Table 2. Clinical Outcomes in PJI Patients Patient Group Number Positive Outcome Satisfactory Outcome Recurrence p-value Early PJI 7 7 (100%) 0 0 0.005 Late PJI 5 4 (80%) 1 (20%) 0 0.03 Total 12 11 (91.7%) 1 (8.3%) 0 < 0.01 The overall success rate of 91.7% demonstrates a high therapeutic efficacy of vancomycinimpregnated bioresorbable gelatin sponges as an adjunct to surgical debridement in PJI management. The absence of reinfection across all patients underscores the effectiveness of localized antibiotic delivery in suppressing residual bacterial load. Rapid normalization of SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 202 inflammatory markers supports the biochemical effectiveness of the method. Outcome differences between early and late PJI are clinically meaningful and align with established infection biology, particularly regarding biofilm maturity. Discussion The findings of this investigation clearly demonstrate that the use of vancomycinimpregnated biodegradable gelatin sponges for localized antibiotic delivery represents a highly effective adjunct modality in the treatment of periprosthetic joint infection (PJI) following total hip arthroplasty. In our cohort, 91.7% of patients achieved a favorable clinical response, characterized by complete eradication of infection, absence of subsequent recurrence, and restoration of joint function. Such a high success rate underscores the strong therapeutic potential of this approach, especially when compared with traditional PJI management strategies. Comparison with Conventional Treatment Approaches Conventional treatment regimens for PJI typically rely on:  systemic intravenous antibiotic therapy,  surgical debridement,  implant retention or staged revision. These traditional strategies have historically been associated with recurrence rates ranging from 20% to 30%, prolonged inpatient care, and a notable burden of systemic adverse effects, particularly nephrotoxicity linked to high-dose intravenous vancomycin therapy [8]. In contrast, our study recorded zero recurrence cases, a result likely attributable to the high sustained concentration of vancomycin released directly at the site of infection by the biodegradable sponges. This level of localized exposure surpasses what is safely achievable via systemic administration, enabling more effective suppression of bacterial biofilms—a major barrier to treatment success in PJI. Key Advantages of the Investigated Method 1. Localized Antibiotic Delivery Bioresorbable sponges ensure that a high concentration of vancomycin is maintained directly within the infected surgical bed, significantly increasing antimicrobial activity against mature biofilms. Biofilms, which provide bacteria with protective barriers against both antibiotics and host immune responses, are a central mechanism of chronic infection persistence [9]. 2. Reduced Risk of Systemic Toxicity Since vancomycin is released locally and only in minimal quantities reaches systemic circulation, the risk of dose-dependent complications such as:  nephrotoxicity,  ototoxicity,  infusion-related reactions is markedly reduced. 3. Practical and Procedural Convenience The use of these gelatin sponges integrates seamlessly with standard surgical workflows. No additional devices or complex preparation steps are necessary, and unlike PMMA beads, these biodegradable carriers do not require a second surgical procedure for removal. Comparison with Other Local Antibiotic Delivery Systems (Table 3) Blersch et al. (2024) reported positive outcomes using multi-antibiotic-loaded bone cement spacers in septic revision arthroplasty, demonstrating high implant survival and infection eradication rates [10]. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 203 Popa et al. also highlighted that biodegradable carriers such as calcium sulfate beads can reduce recurrence and improve outcomes, owing to their ability to release antibiotics in a sustained manner [11]. Table 3. Comparison with Other Localized Antibiotic Delivery Methods Feature Vancomycin-Impregnated Gelatin Sponges PMMA Beads Systemic Vancomycin Biodegradability Yes (~2 weeks) No N/A Surgical Removal Needed No Yes No Sustained Antibiotic Release Yes Yes No Biofilm Penetration High Moderate Low Systemic Side Effects Minimal Minimal High Biodegradability: Gelatin sponges naturally dissolve within approximately two weeks, eliminating the need for reoperation. In contrast, PMMA beads remain inert and require surgical extraction, increasing patient morbidity and procedural cost. Sustained Release: Both gelatin and PMMA can provide controlled antibiotic elution, but only gelatin sponges biodegrade, preventing long-term foreign-body presence. Biofilm Penetration: Gelatin-based carriers allow the release of vancomycin in high local concentrations capable of penetrating and disrupting biofilms. Systemic vancomycin rarely achieves such concentrations at the prosthesis surface. Systemic Safety: Localized vancomycin significantly reduces systemic exposure, while intravenous therapy is well-known for nephrotoxic and ototoxic complications. Integration with Current Literature Steadman et al. (2023) reviewed multiple randomized and observational studies and found that antibiotic-loaded beads and spacers were associated with recurrence rates of ~15%, lower than those observed with systemic treatment alone (~30%) [12]. This aligns with our findings of zero recurrence, suggesting that well-optimized, biodegradable, localized delivery may play an increasingly central role in PJI management. Rottier et al. (2023) emphasized the need for biofilm-active antimicrobial regimens, particularly those capable of targeting metabolically dormant bacterial populations hidden within established biofilms [13]. Vancomycin, when delivered at sustained high concentrations locally, provides exactly such activity. Our study confirms the feasibility and therapeutic superiority of vancomycin-impregnated biodegradable gelatin sponges for managing periprosthetic infections. This technique:  provides extended local antibiotic exposure,  targets biofilm-embedded pathogens,  avoids foreign-body retention,  reduces systemic toxicity,  decreases recurrence risk. Future research directions may include:  optimization of sponge formulation (e.g., dual-antibiotic combinations),  larger randomized controlled trials,  evaluation in chronic infections such as osteomyelitis, SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 11 NOVEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 204  applications in soft tissue infections,  analysis of cost-effectiveness, given the high economic burden of PJI. Conclusion The use of biodegradable gelatin sponges loaded with vancomycin for localized antibiotic administration represents a highly effective and innovative strategy for managing periprosthetic hip joint infections. This technique allows for maximally concentrated delivery of antibiotics directly at the infection site, enhancing bacterial eradication while simultaneously reducing systemic exposure and associated adverse effects. 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