Defensive antibacterial coating in orthopaedic surgery: Current evidence and future direction

Abstract

Periprosthetic joint infections contribute significantly to patient morbidity, prolonged hospital stays, and escalating healthcare costs. Defensive antibacterial coating (DAC^®) hydrogel has emerged as a promising strategy to combat these infections. It forms a biodegradable barrier that reduces bacterial adhesion and can deliver local antibiotics, thereby addressing a key mechanism in biofilm formation. Early clinical evidence suggests that DAC^® effectively lowers infection recurrence in revision hip and knee arthroplasties, with additional benefits in trauma procedures and soft tissue repairs. Moreover, it has demonstrated compatibility with existing implants and surgical techniques, while potentially reducing overall antibiotic use and hospital stays. Despite these encouraging findings, data for its use in primary arthroplasty remains limited, underscoring the need for large-scale, high-quality studies. Future research is poised to refine DAC^®’s antimicrobial efficacy through novel antibiotic combinations, personalised delivery systems, and broader applications beyond lower limb procedures. As the prevalence of comorbidities continues to rise, DAC^® represents a valuable addition to multifaceted infection control protocols, potentially transforming orthopaedic care by enhancing patient outcomes and mitigating the economic and clinical burden of implant-related infections.

Key Words: Hospital-acquired infections; Surgical site infections; Periprosthetic joint infections; Implant-related infections; Orthopaedic surgery; Antibiotic prophylaxis; Defensive antibacterial coating; Biofilm prevention; Revision arthroplasty; Patient outcomes

Core Tip: Orthopaedic implant-related infections, including prosthetic joint and osteosynthesis-associated infections, significantly burden healthcare systems clinically and economically. Defensive antibacterial coating (DAC^®) hydrogel emerges as a promising bioresorbable adjunct to traditional prophylactic strategies, effectively reducing infection rates and antibiotic overuse in orthopaedic surgery. While robust evidence supports DAC^® in revision arthroplasty and trauma surgery, further high-quality studies are needed to confirm its role in primary joint replacement and expand applications to diverse patient populations and anatomical sites.

INTRODUCTION

Hospital-acquired infections (HAIs) continue to impose a significant burden on healthcare systems worldwide due in increasing rates of antibiotic resistance[1,2]. In highincome countries, roughly 5.7%-7% of patients develop at least one healthcareassociated infection (HAI) during their hospital stay. The proportion rises to about 15%-19.2% in low and middleincome countries. Altogether, HAIs are responsible for an estimated 16 million additional hospitaldays in Europe each year[3-6]. Furthermore, the prevalence of HAIs has been increasing by 0.06% annually, with the highest rates observed in lower income regions[7]. Surgical site infections (SSIs), a common type of HAI, have been associated with increased healthcare costs due to additional treatments and extended patient recovery[8]. Some estimates are that 11 out of every 100 surgical patients may develop an SSI within 30 days post-operation[9]. SSIs significantly impact patient outcomes and healthcare systems in trauma and orthopaedic surgery.

Prosthetic joint infections (PJIs) represent a particularly challenging subset of SSIs, carrying substantial clinical and economic consequences in orthopaedic surgery. The incidence of PJIs in orthopaedics is estimated between 1% and 2%, and with the increasing number of orthopaedic surgeries performed annually, the absolute number of PJI cases is on the rise[10,11]. These infections lead to considerable patient morbidity, manifesting as prolonged pain, diminished joint function, and elevated mortality rates[12,13]. Notably, patients with PJIs have up to a five-fold higher mortality rate compared to those undergoing uninfected primary arthroplasties[14]. Similarly, osteosynthesis-associated infections (OAIs) remain a significant concern, with infection rates varying from 1% to 5% following closed fractures and escalating up to 30% after open fractures[15]. These infections can impair bone healing due to prolonged inflammatory processes, increasing the risk of functional loss or even amputation of the affected limb[16]. The rising incidence of these infections underscores the necessity for improved preventive and therapeutic strategies to enhance patient outcomes and alleviate the associated healthcare burden.

In addition to the clinical burden, PJIs and OAIs impose a significant economic strain on healthcare systems. In the United Kingdom, the cost of a single revision total hip replacement due to PJI can reach £42000, compared to approximately £7000 for a primary procedure[17]. Nationally, the annual expenditure on managing these infections exceeds £300 million, reflecting the substantial allocation of healthcare resources required[18]. By 2030, the cumulative cost associated with PJIs in the UK is projected to surpass £1 billion if current trends continue[19]. Similarly, in the United States, the combined annual hospital costs related to PJIs of the hip and knee are estimated to reach $1.85 billion by 2030[20]. Furthermore, an aging population inherently leads to a higher number of joint arthroplasties; projections indicate that primary total knee arthroplasty procedures will increase by 143% and total hip arthroplasties by 75% between 2014 and 2030[21]. This trend necessitates heightened vigilance and the development of tailored preventive measures to address the evolving risk profile of the patient population undergoing orthopaedic procedures

Established strategies to mitigate SSIs in orthopaedics include perioperative antibiotic prophylaxis, judicious hair removal, optimisation of glycaemic control, and topical skin preparations[22]. Additionally, laminar airflow (LAF) ventilation systems have been widely implemented in orthopaedic operating rooms with the aim of reducing SSIs by minimising airborne microbial contamination. However, recent studies have questioned their effectiveness, with recent evidence indicates that LAF systems do not significantly reduce the incidence of SSIs in orthopaedic surgeries and may not be cost-effective[23,24].

The Defensive antibacterial coating (DAC^®) hydrogel has emerged as a promising innovation in reducing periprosthetic joint and osteosynthesis related infections across various patient groups[25,26]. This bioresorbable hydrogel is composed of two polymers: Hyaluronic acid and poly-D,L-lactide. Together, they form a biodegradable coating that can be applied to orthopaedic metalwork and soft tissue during surgery (Figure 1)[27]. The hydrogel functions by creating a physical barrier that inhibits bacterial adhesion to the hydrophobic surfaces of implants-a critical initial step in the development of biofilm-related infections[28]. Additionally, DAC^® hydrogel can act as a carrier for antibiotics, facilitating their localized delivery and sustained release at the surgical site[29]. The aim of this review is to evaluate the role of DAC^® in orthopaedic surgery, examining current evidence, identifying knowledge gaps, and clarifying the technology’s potential to reduce infection risk, minimise antibiotic overuse, and improve patient outcomes across diverse musculoskeletal surgical applications, with an emphasis on future directions.

Figure 1 Defensive antibacterial coating (DAC^®) hydrogel kit shown in its original sterile peel-pouch packaging. The single-use, pre-filled 3 mL syringe is wrapped to preserve sterility until opened in the operating theatre.

REVISION

Hip

Despite routine systemic antibiotic prophylaxis and advancements in surgical techniques, PJI continues to be a significant cause of total hip arthroplasty (THA) failure, with recent evidence suggesting a underestimation of PJI on national registry data[30]. Current research using DAC^® has particularly targeted its application in revision THA procedures for periprosthetic hip infections. This focus arises from the recognition that reinfection following revision surgery poses serious health risks to patients and places considerable economic strain on healthcare systems.

Emerging evidence has assessed the efficacy of DAC^® in one-stage THA. Pellegrini and Legnani[31] reported complete infection eradication in a series of ten patients undergoing cementless one-stage revision THA with DAC^®-coated implants. Similarly, Capuano and colleagues observed successful infection control in all five patients treated using DAC^®-coated prostheses in single-stage revision procedures, reinforcing DAC^®’s potential as an effective adjunct in managing periprosthetic joint infections[32]. These findings suggest that DAC^® may enhance infection prevention in one-stage hip revisions; however, larger-scale studies are needed to confirm these results.

DAC^® has also shown promise in two-stage hip revision surgeries. In a cohort of 28 patients undergoing two-stage cementless hip revisions with DAC^®-coated implants only 2 cases had recurrence and no loosening or failure in the remaining 26 patients[33]. Another study involving 21 patients who received silver-coated mega prostheses for infected hip arthroplasties with severe femoral bone loss reported an infection eradication rate of 90.5% at an approximately mean 5-year follow-up[34]. These findings suggest that DAC^®, including silver coatings, may enhance infection control in two-stage hip revision procedures.

Furthermore SINBIOSE-H trial is currently evaluating the effectiveness of single-stage surgery using DAC^® combined with antibiotic-loaded hydrogels compared to traditional two-stage procedures. This multicentre, prospective, randomised trial hypothesises that single-stage surgery with DAC^®-coated implants is non-inferior regarding infection control while potentially reducing complications, patient morbidity, and healthcare costs associated with prolonged hospitalisation and two-stage interventions[35].

Knee

Similar to PJI of the hip, revision surgeries for PJI of the knee remain a significant economic burden for both patients and healthcare systems worldwide[36]. Encouraging evidence has emerged demonstrating promising results for the use of DAC^® in managing periprosthetic infections of the knee[36,37]. In a case-control study involving 17 knee revisions treated with DAC^®-coated implants, infection recurrence occurred in 9.1% of cases at a mean follow-up of 29.3 months, compared to 13.6% in patients undergoing two-stage revisions without DAC^®. Notably, DAC^® significantly reduced hospital stay and antibiotic treatment duration, suggesting that DAC^®-coated implants effectively control infection while reducing patient morbidity and healthcare costs[32].

PRIMARY ARTHROPLASTY

Current research specifically assessing DAC^® in primary hip arthroplasty remains limited. The majority of evidence predominantly focuses on antibiotic-loaded cement systems such as polymethylmethacrylate, which have shown efficacy in reducing infection rates in cemented implants, notably with infection reductions of approximately 50% when combined with systemic prophylaxis. However, the increasing preference for cementless implants highlights a gap in infection prophylaxis strategies[38]. A clinical trial of DAC^®-coated implants showed a significant reduction in early SSIs in primary hip arthroplasty, from 3% in controls to 0.7% in the DAC^® group, without adverse events or impaired osteointegration[26]. Despite these promising findings, DAC^® has less published evidence when compared to extensively studied antibiotic-loaded cement systems, which continue to dominate clinical practice due to robust data supporting their efficacy in reducing infection and associated complications[26].

In a recent biomechanical study by Orfanos et al[39], the effect of adjuvant antibiotic-loaded hydrogel on uncemented hip stem stability. Using synthetic femora, the study found that axial stiffness was slightly higher in the hydrogel group (4588 ± 448 N/mm) vs the control (4176 ± 240 N/mm). Additionally, while stem subsidence increased with load in both groups, no significant differences were observed between them. Importantly, the hydrogel was distributed homogeneously around the implant, suggesting that its use for local antibiotic delivery does not compromise the primary mechanical stability of uncemented hip stems. These results support the potential of adjuvant antibiotic-loaded hydrogel as a feasible strategy for infection prophylaxis in hip arthroplasty revisions without adversely affecting implant fixation.

TRAUMA

DAC^® has emerged as a promising strategy to prevent implant-related infections in orthopaedic trauma surgery[40]. In a multicentre randomised controlled trial involving 256 patients undergoing internal fixation for closed fractures, the application of antibiotic-loaded DAC^® resulted in a significant reduction in SSI where no infections were observed in the DAC^®-treated group[41]. Further supporting these findings, a retrospective observational study assessed the efficacy of DAC^® in preventing fracture-related infections (FRIs) among 27 high-risk patients. The study reported only one case of FRI (2.94%) at five months post-surgery, suggesting that local antibiotic prophylaxis with DAC^® effectively reduces infection incidence compared to the estimated preoperative risk[42].

These studies highlight the potential of DAC^® as an effective adjunctive measure in reducing infection rates in orthopaedic trauma surgeries. Its application has demonstrated a significant decrease in both SSIs and FRIs, underscoring its value in clinical practice.

SOFT TISSUE

Achilles tendon repair

Infections following surgical repair of the Achilles tendon are challenging complications that can compromise tendon healing and function. A study by Babiak et al[43] investigated the use of DAC^® hydrogel loaded with gentamicin and vancomycin in eight patients with postoperative infections without significant soft tissue defects. The treatment involved debridement of the infected area followed by application of 5 mL DAC^® hydrogel containing 160 mg gentamicin and 50 mg vancomycin. Over a follow-up period ranging from 6 to 43 months, all patients achieved complete resolution of the infection, with no adverse effects related to the hydrogel reported indicating the potential benefit in soft tissue foot and ankle surgery.

Anterior cruciate ligament reconstruction

Anterior cruciate ligament (ACL) reconstruction is a common procedure with a risk of postoperative infections, though relatively low, such infections can lead to graft failure and poor clinical outcomes. A feasibility study by Aicale et al[44] assessed the safety and efficacy of DAC^® hydrogel with vancomycin applied to hamstring tendon autografts during ACL reconstruction. The study included patients undergoing ACL reconstruction with semitendinosus and gracilis tendon autografts. The application of DAC^® hydrogel was found to be safe, with no adverse events reported, and effective in preventing early SSIs.

SPINES

DAC^® has been investigated for its potential to reduce SSI in spinal surgery. Parbonetti et al[45] conducted a study involving 73 patients undergoing instrumented vertebral surgery for degenerative spinal disorders. They reported an infection rate of 0% in the DAC^®-treated group, compared to 2.94% in posterior cervical surgeries without DAC^®. Another study highlighted that spinal implant infections occur in 0.7% to 11.9% of cases, underscoring the need for effective preventive measures. These findings suggest that DAC^® may significantly lower infection rates in spinal procedures.

FUTURE DIRECTION

The future application of DAC^® in orthopaedic trauma patients with multiple comorbidities appears promising, especially given the increasing complexity of patient profiles. Patients with diabetes, cardiovascular disease, chronic kidney disease, and immunosuppressive conditions experience significantly elevated risks for SSI and FRIs due to compromised immune responses and impaired wound healing processes[46]. As DAC^® hydrogels have demonstrated efficacy in reducing implant-related infections in trauma settings, their proactive application could substantially improve outcomes in this vulnerable group[47]. Future research must focus on personalised antibiotic loading tailored to specific microbial profiles and resistance patterns, optimising efficacy while minimising risks of resistance[48]. Additionally, long-term clinical trials examining DAC^® effectiveness specifically in trauma patients with significant comorbidities are essential to fully establish its role in routine clinical practice and potentially reduce healthcare costs associated with complications.

While current evidence regarding DAC^® has demonstrated promising outcomes in revision arthroplasty, particularly in reducing infection rates, there remains limited data evaluating its efficacy in primary arthroplasty of the hip and knee[47]. Given the considerable clinical and economic implications of PJIs, further high-quality, randomised controlled trials are required to conclusively establish the benefits of DAC^® in primary joint replacement settings[49]. Additionally, the application of DAC^® should extend beyond hip and knee arthroplasty, encompassing other joint replacements, such as shoulders, elbows, and ankles, where the burden of infection can have significant functional and quality-of-life consequences[50-52]. Future research must particularly target patient populations identified as high-risk, including those with diabetes, immunosuppression, obesity, or prior joint infections, who stand to gain substantially from improved infection prophylaxis. As DAC^® evolves, continued technological advancements will enhance its antimicrobial efficacy and biocompatibility, further integrating such strategies into routine orthopaedic practice[53]. Ultimately, robust, multi-centre collaborative studies will be critical in determining the precise role and cost-effectiveness of DAC across various arthroplasty procedures, facilitating evidence-based implementation into clinical pathways to improve patient outcomes[47].

Next-generation DAC^® hydrogels are emerging as a promising strategy for infection prophylaxis and treatment in orthopaedics, particularly for patients at high risk of infection or those harbouring multidrug-resistant organisms[54]. Ongoing research into novel antibiotic combinations and adjunct anti-biofilm therapies aims to enhance both short- and long-term effectiveness of these treatments. For instance, studies have demonstrated that combining bacteriophages with antibiotics can effectively disrupt biofilms, making bacteria more susceptible to treatment. Additionally, the development of multifunctional hydrogels incorporating antimicrobial agents, such as curcumin, shows potential in preventing and controlling periprosthetic joint infections[55,56]. Expanding the application of DAC^® technologies to diverse anatomical sites beyond hip, knee, and shoulder arthroplasty-such as the spine and foot–ankle joints-needs further direction.

CONCLUSION

The application of DAC^® represents a significant advancement in the management of implant-related infections across various orthopaedic disciplines. This review highlights that, despite the persistent challenge of hospital-acquired infections and their associated clinical and economic burdens, DAC^® hydrogel offers promising results in reducing the incidence of SSIs from primary arthroplasty to revision surgeries, trauma cases, and soft tissue repairs.

Moreover, the future direction of DAC^® technology appears clear, with the potential for personalised antibiotic loading and integration with novel antimicrobial agents. Such innovations could expand its application to underexplored areas like shoulder, ankle, and hand surgeries, as well as soft tissue repairs. Addressing the growing complexity of patient profiles, especially in populations with multiple comorbidities, will be critical in optimising these strategies.

Ultimately, this review underscores the transformative potential of DAC^® in orthopaedic infection prophylaxis. As further clinical trials and biomechanical studies refine its use, DAC^® is poised to become an integral component of comprehensive infection control protocols, thereby improving both the quality of care and long-term patient outcomes in orthopaedic practice.