Musculoskeletal Wound Research Articles

Advancements in vacuum therapy for musculoskeletal wound care: A comprehensive analysis of chronic wounds and acute injuries

Musculoskeletal wounds are challenging to treat. Vacuum therapy (VT), based on the principle of applying negative pressure to a wound, has gained popularity as an adjunctive treatment modality for musculoskeletal wounds. Clinical studies have shown that VT improves wound bed preparation, reduces wound size, accelerates healing rates, and decreases time to wound closure. It is also associated with a lower risk of wound complications, such as infection, dehiscence, and seroma formation. The integration of VT into a comprehensive wound management approach has the potential to improve outcomes for patients with musculoskeletal wounds. This review provides a comprehensive overview of VT for musculoskeletal wound care. The review discusses the current practices, mechanism of action, benefits, risks, and future directions of VT. The review concludes that VT is a valuable tool for the treatment of musculoskeletal wounds, and that it is safe and effective for most patients.

Innovative approaches in equine wound management: Addressing challenges and their remedies

Horses are highly susceptible to musculoskeletal wounds due to the demands of their work, whether in transportation or as athletes. These wounds significantly impact the overall performance of horses, emphasizing the importance of effective wound management for optimal functionality. Among equine wounds, distal limb injuries are prevalent, accounting for over 60% of all cases. However, managing wounds in these extremities poses considerable challenges, as poor healing often leads to the formation of exuberant granulation tissue. In equine practice, biofilms are frequently observed in wounds with delayed healing, and there is an alarming rise in the incidence of multi-drug-resistant microbial strains. Consequently, there is an urgent need to implement advanced strategies in wound care management to address these clinical scenarios effectively. Maintaining the soundness of the musculoskeletal system is crucial for horses, particularly those destined for athletic careers. Thus, ongoing trials in equine clinical practice aim to explore innovative approaches for achieving effective wound healing. This article highlights the importance of innovative strategies in equine wound management and emphasizes the need to address challenges such as exuberant granulation tissue formation, biofilm presence, and multi-drug-resistant microbes. By implementing these innovative approaches, equine clinicians can enhance wound healing outcomes and ensure the optimal health and performance of horses.

Effectiveness of Negative Pressure Wound Therapy During Aeromedical Evacuation Following Soft Tissue Injury and Infection.

Negative pressure wound therapy (NPWT) is utilized early after soft tissue injury to promote tissue granulation and wound contraction. Early post-injury transfers via aeromedical evacuation (AE) to definitive care centers may actually induce wound bacterial proliferation. However, the effectiveness of NPWT or instillation NPWT in limiting bacterial proliferation during post-injury AE has not been studied. We hypothesized that instillation NPWT during simulated AE would decrease bacterial colonization within simple and complex soft tissue wounds. The porcine models were anesthetized before any experiments. For the simple tissue wound model, two 4-cm dorsal wounds were created in 34.9 ± 0.6 kg pigs and were inoculated with Acinetobacter baumannii (AB) or Staphylococcus aureus 24 hours before a 4-hour simulated AE or ground control. During AE, animals were randomized to one of the five groups: wet-to-dry (WTD) dressing, NPWT, instillation NPWT with normal saline (NS-NPWT), instillation NPWT with Normosol-R® (NM-NPWT), and RX-4-NPWT with the RX-4 system. For the complex musculoskeletal wound, hind-limb wounds in the skin, subcutaneous tissue, peroneus tertius muscle, and tibia were created and inoculated with AB 24 hours before simulated AE with WTD or RX-4-NPWT dressings. Blood samples were collected at baseline, pre-flight, and 72 hours post-flight for inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor alpha. Wound biopsies were obtained at 24 hours and 72 hours post-flight, and the bacteria were quantified. Vital signs were measured continuously during simulated AE and at each wound reassessment. No significant differences in hemodynamics or serum cytokines were noted between ground or simulated flight groups or over time in either wound model. Simulated AE alone did not affect bacterial proliferation compared to ground controls. The simple tissue wound arm demonstrated a significant decrease in Staphylococcus aureus and AB colony-forming units at 72 hours after simulated AE using RX-4-NPWT. NS-NPWT during AE more effectively prevented bacterial proliferation than the WTD dressing. There was no difference in colony-forming units among the various treatment groups at the ground level. The hypoxic, hypobaric environment of AE did not independently affect the bacterial growth after simple tissue wound or complex musculoskeletal wound. RX-4-NPWT provided the most effective bacterial reduction following simulated AE, followed by NS-NPWT. Future research will be necessary to determine ideal instillation fluids, negative pressure settings, and dressing change frequency before and during AE.

Topical oxygen therapy in acute traumatic musculoskeletal wounds of the foot and ankle

To quantify the reduction in wound size and change in wound quality following low-cost topical oxygen therapy (TOT) in patients with acute traumatic musculoskeletal wounds of the foot and ankle. This prospective interventional study included patients with acute traumatic musculoskeletal wounds of the foot and ankle of <3 weeks' duration after they had undergone debridement and required subsequent wound coverage. A sterile C-Arm cover was used to cover the wound and 100% oxygen was administered at 1 atm, at a rate of 10l/min for 90 minutes on each of four consecutive days, through a suction catheter connected to an oxygen cylinder. The cycle was repeated after a three-day break. Wound surface area (by plotting on graph paper) and wound quality (by modified wound infection checklist score and swabs for culture and Gram staining) were assessed before and after TOT application. The study cohort included 20 patients ≥18 years of age. There was a statistically significant (p<0.001) reduction in mean wound surface area from 79.3cm2 at baseline to 69.6cm2 after two cycles of TOT. The mean modified wound infection checklist score was 13.6 and 0.8, respectively, before and after two cycles of TOT, suggesting statistically significant improvement (p=0.02) in wound quality. All patients showed no growth in their wound culture after TOT. TOT appears to be a promising and cost-effective alternative in the management of traumatic wounds. However, future studies with larger sample sizes and control groups for comparison are needed to establish the benefit of TOT in acute traumatic musculoskeletal wounds.

Preclinical evaluation of a commercially available biofilm disrupting wound lavage for musculoskeletal trauma

BackgroundTreatment of open fractures remains a significant challenge in trauma care as these fractures are accompanied by extensive soft tissue damage, exposing the wound site to contaminants and increasing infection risk. Formation of biofilm, a capsule-like environment that acts as a barrier to treatment, is a primary mode by which infecting pathogens persist at the wound site. Therefore, a pressing need exists to identify irrigation methods that can disrupt biofilm and expose pathogens to treatment. This study aims to evaluate the antibiofilm wound lavage, Bactisure™, in comparison with saline for care of severe musculoskeletal wounds and elucidate potential effects on antibiotic treatment success.MethodsUAMS-1 Staphylococcus aureus biofilms were formed in vitro and treated with Bactisure™ wound lavage or sterile normal saline, alone, or in combination with sub-biofilm inhibitory levels of vancomycin. Characterization methods included quantification of biofilm biomass, quantification of viable biofilm bacteria, and biofilm matrix imaging. For in vivo assessment, a delayed treatment model of contaminated open fracture was used wherein a critical-sized defect was created in a rat femur and wound site inoculated with UAMS-1. Following a 6 h delay, wounds were debrided, irrigated with lavage of interest, and antibiotic treatments administered. Bacterial enumeration was performed on bone and hardware samples after two weeks.ResultsAn immediate reduction in biofilm biomass was observed in vitro following antibiofilm lavage treatment, with a subsequent 2- to 3- log reduction in viable bacteria achieved after 24 h. Furthermore, biofilms treated with antibiofilm lavage in combination with vancomycin exhibited a minor, but statistically significant, decrease in viable bacteria compared to irrigation alone. In vivo, a minor, not statistically significant, decrease in median bioburden was observed for the antibiofilm lavage compared to saline when used in combination with antibiotics. However, the percentage of bone and hardware samples with detectable bacteria was reduced from 50 to 38%.ConclusionsThese results suggest that the antibiofilm wound lavage, Bactisure™, may hold promise in mitigating infection in contaminated musculoskeletal wounds and warrants further investigation. Here, we proposed multiple mechanisms in vitro by which this antibiofilm lavage may help mitigate infection, and demonstrate this treatment slightly outperforms saline in controlling bioburden in vivo.

Change in granulation tissue coverage and bacteriological load using Low Cost Negative Pressure Wound Therapy in acute musculoskeletal wounds

BackgroundLow cost Negative Pressure Wound Therapy (NPWT) dressings have been considered as an alternative to traditional daily dressings. There is scanty literature evaluating the change in the percentage area of wound covered by granulation tissue following application of low-cost NPWT. The change in the bacteriological flora following application of low-cost NPWT devices has also not been evaluated. MethodsPatients above the age of 18 years with acute musculoskeletal injuries of <3 weeks duration which underwent a surgical debridement and required subsequent wound coverage were included in the study. Area of the wound and the area covered by the granulation tissue as well as the bacteriological count were measured before and after application of NPWT. A low cost NPWT using wall mounted vacuum device was put on the patient giving a constant negative pressure of 125 mm of Hg for 2 days. The findings before and after application of NPWT were compared and analyzed using Wilcoxin Signed-rank test. Results21 patients with mean age of 35.52±15.075 were included. The pre-NPWT granulation tissue area ranged from 122 mm2 to 8483 mm2 with a mean of 1648.38 mm2 (SD = 1933.866). The post-NPWT granulation tissue area ranged from 234 mm2 to 7847 mm2 with a mean of 2364.48 mm2 (SD = 1857.716). The mean increase in granulation tissue was 716.1 mm2.The pre-NPWT wound area ranged from 422 mm2 to 10847 mm2 with a mean of 4009.62 mm2 (SD = 3026.209). The post-NPWT wound area ranged from 326 mm2 to 9143 mm2 with a mean of 3410.33 mm2 (SD = 2636.206). The mean reduction in wound size was 599.29 mm2.The pre-NPWT bacteriological count ranged from 3000/ml to 130000000/ml with a mean of 12616761.90/ml (SD = 29664589.37). The post-NPWT bacteriological count ranged from 1000/ml to 380000000/ml with a mean of 26401523.81/ml. The mean increase in bacteriological count was 13784761.91/ml. ConclusionThere was a statistically significant decrease in wound size (p = 0.001) and statistically significant increase in percentage area of granulation tissue coverage (p = 0.000) following low cost NPWT application. However there was no statistically significant increase in bacteriological clearance in these patients.

Negative pressure wound therapy does not diminish efficacy of topical antibiotic powder in a preclinical contaminated wound model.

AimsHigh-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder.MethodsComplex musculoskeletal wounds were created in goats and inoculated with a strain of Staphylococcus aureus modified to emit light. Six hours after contaminating the wounds, imaging, irrigation, and debridement and treatment application were performed. Animals received either vancomycin powder with a wound pouch dressing or vancomycin powder with NPWT.ResultsThere were no differences in eradication of bacteria when vancomycin powder was used in combination with NPWT (4.5% of baseline) compared to vancomycin powder with a wound pouch dressing (1.7% of baseline) (p = 0.986), even though approximately 50% of the vancomycin was recovered in the NPWT exudate canister.ConclusionThe antimicrobial efficacy of the vancomycin powder was not diminished by the application of NPWT. These topical and locally applied therapies are potentially effective tools that can provide quick, simple treatments to prevent infection while providing coverage. By reducing the occurrence of infection, the recovery is shortened, leading to an overall improvement in quality of life.Cite this article: Bone Joint Res 2021;10(2):149–155.

The Impact of Modern Therapeutic Methods on the Oxidant-Antioxidant Equilibrium and Activities of Selected Lysosomal Enzymes and Serine Protease Inhibitor in Amateur Athletes.

Deep electromagnetic stimulation (DEMS) and low-frequency ultrasound (US) are new physical therapy methods used in the rehabilitation of the musculoskeletal system and wound healing. They are applied locally to treat the injured tissues. The beneficial effects of these methods in supportive care have been documented, but accurate biochemical effects are not known. The goal was to assess the effect of single DEMS and US sessions on the oxidant-antioxidant equilibrium, as well as the activities of lysosomal hydrolases and α1-antitrypsin (AAT) in peripheral blood of juvenile injured amateur athletes. In the athletes with low back pain (DEMS treated, N = 16) and pain in the shoulder or ankle joint (US treated, N = 14), as well as in healthy control amateur athletes (DEMS treated, N = 14; US treated, N = 17), before the sessions and 30 minutes and 24 hours after them, the levels of the following parameters were determined: thiobarbituric acid reactive substances (TBARS) in erythrocytes and plasma, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in erythrocytes, as well as acid phosphatase (AcP), arylsulfatase (ASA), cathepsin D (CTS D), and α1-antitrypsin (AAT) in serum. After both procedures, the levels of parameters changed in a negligible manner, excluding the cathepsin D activity, which was statistically significantly lower 30 min and 24 h after US in the control athletes compared to the baseline activity determined directly before the procedure (47.5% and 55.7% differences, respectively). Similar tendency was observed after DEMS (p > 0.05). The procedures, especially low-frequency US, decrease lysosomal proteolytic activity and do not significantly disrupt the oxidant-antioxidant and lysosomal equilibriums in the peripheral blood both of healthy and injured athletes. No systemic acute-phase response of AAT was also detected in the athletes after both procedures. This trial is registered with CTRI/2018/01/011344.

Tattoos among athletes: a matter of concern?

Ten to 30% of the population is currently tattooed. This trend does not spare athletes and sports medicine specialists may have to manage tattooed athletes. The purpose of this study was to review the possible issues associated with tattoos among athletes. Overall, tattooed athletes are exposed to the same complications as anyone, mainly healing issues, skin infections and allergic reactions to a tattoo color. Besides, the main pitfall in sports medicine remains invasive gestures such as puncture or infiltration, as they must be avoided at all cost if the tattoo is recent and under healing. Issues associated with imaging are rather limited (artifacts, visible calcification). Burns during magnetic resonance imagining may occur but they are rather rare. Local neuromuscular complications attributable to tattooing are exceptional. Whether tattoos may have a "systemic" impact on the prevalence of unexplained symptoms in athletes (fatigue, distant tendon or musculoskeletal wounds) remain unknown.

Time Course of Immune Response and Immunomodulation During Normal and Delayed Healing of Musculoskeletal Wounds.

Single trauma injuries or isolated fractures are often manageable and generally heal without complications. In contrast, high-energy trauma results in multi/poly-trauma injury patterns presenting imbalanced pro- and anti- inflammatory responses often leading to immune dysfunction. These injuries often exhibit delayed healing, leading to fibrosis of injury sites and delayed healing of fractures depending on the intensity of the compounding traumas. Immune dysfunction is accompanied by a temporal shift in the innate and adaptive immune cells distribution, triggered by the overwhelming release of an arsenal of inflammatory mediators such as complements, cytokines and damage associated molecular patterns (DAMPs) from necrotic cells. Recent studies have implicated this dysregulated inflammation in the poor prognosis of polytraumatic injuries, however, interventions focusing on immunomodulating inflammatory cellular composition and activation, if administered incorrectly, can result in immune suppression and unintended outcomes. Immunomodulation therapy is promising but should be conducted with consideration for the spatial and temporal distribution of the immune cells during impaired healing. This review describes the current state of knowledge in the spatiotemporal distribution patterns of immune cells at various stages during musculoskeletal wound healing, with a focus on recent advances in the field of Osteoimmunology, a study of the interface between the immune and skeletal systems, in long bone fractures. The goals of this review are to (1) discuss wound and fracture healing processes of normal and delayed healing in skeletal muscles and long bones; (2) provide a balanced perspective on temporal distributions of immune cells and skeletal cells during healing; and (3) highlight recent therapeutic interventions used to improve fracture healing. This review is intended to promote an understanding of the importance of inflammation during normal and delayed wound and fracture healing. Knowledge gained will be instrumental in developing novel immunomodulatory approaches for impaired healing.

Dynamics of the Activity of MAP-Kinase Cascades in the Healing Process of Postoperative Musculocutaneous Wounds

Background. Management of the reparative process is an urgent task of modern medicine. In our opinion, the development of pathogenetically grounded approaches to optimizing the repair process for managing the interrelations of stromal cells is promising. One of the promising areas in this regard is the impact on the MAPK-cascades.Aim: to study the expression of MAP-kinase mechanisms in the regulation of repair by the example of a musculocutaneous wound.Methods. A linear muscular skin wound was modeled using Wistar rats weighing 220–250 g at the age of 9 months (n = 24). Immunofluorescence staining was performed to detect the activity of p38, JNK, and ERK MAPK cascades from 1 to 30 days.Results. It was established that specific staining in the area of connective tissue formation during staining with p38 MAPK and its phosphorylated form was first observed on the 3rd day, and its maximum severity occurred at the same time. On the 7th and 14th day, small zones in the area of scar formation were minimally stained. The phosphorylated part of the JNK-cascade in the zone of traumatic injury was detected starting from the 1st day after the injury. Bright color persisted on the 3rd day. On the 7th day, the color was minimal, and by the 14th day a second wave of expression was observed. ERK-staining was observed from the 1st to the 14th day with a peak activity on the 3rd day.Conclusion. Thus, we revealed the simultaneous involvement of p38, JNK-, and ERK-cascades in the regulation of the reparative process in the conditions of a musculoskeletal wound. At the same time, it is noteworthy that the peak activity of all cascades coincides and falls on the 3rd day.

Topical rifampin powder for orthopaedic trauma part II: Topical rifampin allows for spontaneous bone healing in sterile and contaminated wounds.

Infectious complications can reduce fracture healing rate. Broad spectrum antibiotics are commonly administered to prevent and treat musculoskeletal infections. Local antibiotics are applied to the wound site to increase therapeutic concentrations without increasing systemic toxicity, however, may hinder local tissue recovery. Rifampin has been shown to eradicate mature Staphylococcal biofilms and its use proven for treating musculoskeletal infections. In this study, a spontaneously healing defect model in a rat was used to investigate the impact rifampin powder has on endogenous bone healing in both a sterile and contaminated wound. No significant differences were identified in bone volume fraction via microcomputed tomography, radiological scoring, or histology between an empty defect and animals that received vancomycin or rifampin powder in a sterile wound. When applied to a contaminated musculoskeletal wound, the rifampin powder had significantly greater bone formation compared to the control, as measured by microcomputed tomography, plain radiology, and histology. In addition, the animals treated with rifampin powder had reduced bacteria, reduced white blood cell count and reduced number of clinical indications of infection. Interestingly, while the vancomycin group still displayed signs of infection via quantitative microbiology, plain radiology, and histology, there was significant bone formation within the defect and reduction of systemic signs of infection. We demonstrated that the use of rifampin powder allows bone to heal in both a sterile and contaminated model of musculoskeletal infection. To our knowledge, this is the first time the direct impact of local antibiotics on bone healing has been investigated. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 36:3142-3150, 2018.

Development and Evaluation of an Injectable Chitosan/β-Glycerophosphate Paste as a Local Antibiotic Delivery System for Trauma Care.

Complex open musculoskeletal wounds are a leading cause of morbidity worldwide, partially due to a high risk of bacterial contamination. Local delivery systems may be used as adjunctive therapies to prevent infection, but they may be nondegradable, possess inadequate wound coverage, or migrate from the wound site. To address this issue, a thermo-responsive, injectable chitosan paste was fabricated by incorporating beta-glycerophosphate. The efficacy of thermo-paste as an adjunctive infection prevention tool was evaluated in terms of cytocompatibility, degradation, antibacterial, injectability, and inflammation properties. In vitro studies demonstrated thermo-paste may be loaded with amikacin and vancomycin and release inhibitory levels for at least 3 days. Further, approximately 60% of thermo-paste was enzymatically degraded within 7 days in vitro. The viability of cells exposed to thermo-paste exceeded ISO 10993-5 standards with approximately 73% relative viability of a control chitosan sponge. The ejection force of thermo-paste, approximately 20 N, was lower than previously studied paste formulations and within relevant clinical ejection force ranges. An in vivo murine biocompatibility study demonstrated that thermo-paste induced minimal inflammation after implantation for 7 days, similar to previously developed chitosan pastes. Results from these preliminary preclinical studies indicate that thermo-paste shows promise for further development as an antibiotic delivery system for infection prevention.

Rapid degradation and non-selectivity of Dakin’s solution prevents effectiveness in contaminated musculoskeletal wound models

BackgroundDakin’s solution (buffered sodium hypochlorite) has been used as a topical adjunct for the treatment of invasive fungal infections in trauma patients. Prudent use of Dakin’s solution (DS) for complex musculoskeletal wound management implies balancing antimicrobial efficacy and human tissue toxicity, but little empirical evidence exists to inform clinical practice. To identify potentially efficacious DS concentrations and application methods, we conducted two animal studies to evaluate the ability of DS to reduce bacterial burden in small and large animal models of contaminated musculoskeletal wounds. MethodsAn established rat (Rattus norvegicus) contaminated femoral defect model was employed to evaluate the antimicrobial efficacy of DS as a topical adjunctive treatment for Staphylococcus aureus infection. A range of clinically-relevant DS concentrations (0.00025%–0.125%) were tested, both with and without periodic replenishment during treatment. Next, an established goat (Capra hircus) musculoskeletal wound model, consisting of a Pseudomonas aeruginosa contaminated proximal tibia cortical defect, muscle crush, and thermal injury, was utilized to evaluate the antimicrobial efficacy of dilute DS (0.0025% and 0.025%) as a surgical irrigant solution. In situ reactive chlorine concentrations were monitored throughout each treatment using an automated iodometric titration approach. ResultsIn a rat wound model, DS treatment did not significantly reduce S. aureus bioburden after 14 days as compared to saline control. Two treatment groups (0.01% single application and 0.025% multiple application) exhibited significantly higher bacterial burden than control. In a goat musculoskeletal wound model, neither 0.0025% nor 0.025% DS significantly altered P. aeruginosa bioburden immediately following treatment or at 48 h post-treatment. Overall, DS applied to exposed soft tissue exhibited rapid degradation, e.g., 0.125% DS degraded 32% after 5 s progressing to 86% degradation after 15 min following single application. ConclusionsWe did not observe evidence of a therapeutic benefit following Dakin’s solution treatment for any tested concentration or application method in two contaminated musculoskeletal wound models. Despite confirmation of robust bactericidal activity in vitro, our findings suggest DS at current clinically-used concentrations does not kill tissue surface-attached bacteria, nor does it necessarily cause host tissue toxicity that exacerbates infection in the setting of complex musculoskeletal injury.

An Effective Negative Pressure Wound Therapy–Compatible Local Antibiotic Delivery Device

The current clinical standard for local antibiotic depot is polymethylmethacrylate (PMMA) beads. Unfortunately, these are not ideal and negative pressure wound therapy (NPWT) reduces their limited effectiveness. Recently, a chitosan sponge has been shown to be an effective carrier of antibiotics. Because it acts as a delivery vehicle with increased wound contact area instead of an antibiotic depot, it may be more effective. The objectives of this study were to determine if (1) a chitosan sponge would be more effective than PMMA beads as a local antibiotic delivery device and (2) the chitosan sponge remains an effective method of delivery when used in conjunction with NPWT. Contaminated musculoskeletal wounds were created on the proximal tibia of goats; the animals were assigned to 1 of 4 groups (bead pouch, beads with NPWT, sponge pouch, and sponge with NPWT). The animals were survived for 48 hours, and the bacteria in the wound were quantified. The antibiotic levels in the blood and within the NPWT canisters were measured throughout the study period. After treatment, there were significantly fewer bacteria in wounds treated with antibiotic chitosan sponge delivery than antibiotic PMMA bead depot (P < 0.05), and NPWT did not reduce the effectiveness of the chitosan sponge even though large amounts of vancomycin was found in the canisters. The peak serum levels of vancomycin were well below what is considered safe levels. Antibiotic delivery to the wound using a chitosan sponge is compatible with NPWT and is more effective than PMMA antibiotic depot. The chitosan sponge works in conjunction with NPWT and may improve the outcomes of open fracture wounds.

Pulsatile Lavage of Musculoskeletal Wounds Causes Muscle Necrosis and Dystrophic Calcification in a Rat Model.

Adequate irrigation of open musculoskeletal injuries is considered the standard of care to decrease bacterial load and other contaminants. While the benefit of debris removal compared with the risk of further seeding by high-pressure lavage has been studied, the effects of irrigation on muscle have been infrequently reported. Our aim in the present study was to assess relative damage to muscle by pulsatile lavage compared with bulb-syringe irrigation. In an animal model of heterotopic ossification, 24 Sprague-Dawley rats underwent hindlimb blast amputation via detonation of a submerged explosive, with subsequent through-the-knee surgical amputation proximal to the zone of injury. All wounds were irrigated and underwent primary closure. In 12 of the animals, pulsatile lavage (20 psi [138 kPa]) was used as the irrigation method, and in the other 12 animals, bulb-syringe irrigation was performed. A third group of 6 rats did not undergo the blast procedure but instead underwent surgical incision into the left thigh muscle followed by pulsatile lavage. Serial radiographs of the animals were made to monitor the formation of soft-tissue radiopaque lesions until euthanasia at 6 months. Image-guided muscle biopsies were performed at 8 weeks and 6 months (at euthanasia) on representative animals from each group. Histological analysis was performed with hematoxylin and eosin, alizarin red, and von Kossa staining on interval biopsy and postmortem specimens. All animals managed with pulsatile lavage, with or without blast injury, developed soft-tissue radiopaque lesions, whereas no animal that had bulb-syringe irrigation developed these lesions (p = 0.001). Five of the 12 animals that underwent blast amputation with pulsatile lavage experienced wound complications, whereas no animal in the other 2 groups experienced wound complications (p = 0.014). Radiopaque lesions appeared approximately 10 days postoperatively, increased in density until approximately 16 weeks, then demonstrated signs of variable regression. Histological analysis of interval biopsy and postmortem specimens demonstrated tissue damage with inflammatory cells, cell death, and dystrophic calcification. Pulsatile lavage of musculoskeletal wounds can cause irreversible insult to tissue, resulting in myonecrosis and dystrophic calcification. The benefits and offsetting harm of pulsatile lavage (20 psi) should be considered before its routine use in the management of musculoskeletal wounds.

Determining potential of PMMA as a depot for rifampin to treat recalcitrant orthopaedic infections

BackgroundOpen fractures are often complicated by infection. In cases of severe soft tissue and vascular injury, systemic antibiotics may be ineffective due to their inability to reach and provide direct antimicrobial activity to the zone of injury. High antibiotic concentrations within the wound can be achieved with reduced systemic toxicity by using local antibiotic delivery. As bacteria associated with musculoskeletal injuries frequently form biofilms, antibiotic selection is important. Herein, the use of rifampin, an antibiotic with activity against biofilms, delivered via polymethylmethacrylate (PMMA) beads is evaluated for use in a traumatic musculoskeletal wound model. MethodsPMMA beads loaded with rifampin, or combinations of rifampin and vancomycin, were prepared and evaluated for time to curing, drug release kinetics in vitro, and infection prevention in vivo using a well-established rat model of musculoskeletal infection. A segmental bone defect was created and contaminated with methicillin susceptible Staphylococcus aureus (UAMS-1). Wounds were debrided, irrigated, and treated with PMMA beads, containing rifampin or combinations of rifampin plus vancomycin, following a 6-h (early) or 24-h (delayed) treatment. After 14days, tissue, implants, and beads were removed for bacterial quantification and assessed for rifampin resistance. ResultsThere was a direct association between loaded concentration and release kinetics of the rifampin and vancomycin from PMMA beads. Higher rifampin concentrations delayed PMMA curing times. The addition of vancomycin to PMMA resulted in more rapid release of rifampin from beads. However, the highest concentration of rifampin loaded PMMA beads (10% wt/wt) was the only treatment to significantly reduce bacterial counts. No rifampin resistance was observed. ConclusionAlthough higher concentrations of rifampin resulted in significant reductions of bacteria, these levels extended PMMA curing times and transformed PMMA material characteristics. While these characteristics make the material unsuitable for weight-bearing applications, such as total joint arthroplasty, the use of rifampin-loaded PMMA beads may be an effective intervention in a contaminated traumatic extremity wound due to its ability to eradicate biofilms.

Blended Chitosan Paste for Infection Prevention: Preliminary and Preclinical Evaluations.

Local drug delivery devices offer a promising method for delivering vancomycin and amikacin for musculoskeletal wounds. However, current local delivery devices such as beads and sponges do not necessarily allow for full coverage of a wound surface with eluted antibiotics and do not address the need for reducing the antibiotic diffusion distance to help prevent contamination by bacteria or other microorganisms. We blended chitosan/polyethylene glycol (PEG) pastes/sponges to increase biocompatibility and improve antibiotic coverage within the wound. (1) Are blended chitosan/PEG pastes biodegradable? (2) Are the blended pastes biocompatible? (3) How much force does paste require for placement by injection? (4) Will the pastes elute active antibiotics to inhibit bacteria in vitro? (5) Can the pastes prevent infection in a preclinical model with hardware? Our blended paste/sponge formulations (0.5% acidic, 1% acidic, and acidic/neutral) along with a control neutral 1% chitosan sponge were tested in vitro for degradability, cytocompatibility, injectability tested by determining the amount of force needed to inject the pastes, elution of antibiotics, and activity tested using zone of inhibition studies. Along with these studies, in vivo models for biocompatibility and infection prevention were tested using a rodent model and an infected mouse model with hardware, respectively. By evaluating these characteristics, an improved local drug delivery device can be determined. All three of the paste formulations evaluated were almost fully degraded and with 6 days of degradation, the percent remaining being wasless than that of the control sponge (percent remaining: control 99.251% ± 1.0%; 0.5% acidic 1.6% ± 2.1%, p = 0.002; 1% acidic 1.7% ± 1.6%, p = 0.002; acidic/neutral 2.3% ± 1.7%, p = 0.010). There was good biocompatibility because cell viability in vitro was high (control 100.0 ± 14.3; 0.5% acidic formulation at 79.4 ± 12.6, p < 0.001; 1% acidic formulation at 98.6 ± 6.1, p = 0.993; acidic/neutral formulation at 106.7 ± 12.8, p = 0.543), and in vivo inflammation was moderate (control 2.1 ± 1.2; 0.5% acidic 3.3 ± 0.2, p = 0.530; 1% acidic 2.5 ± 0.9, p = 0.657; acidic/neutral 2.9 ± 1.1, p = 0.784). Force required to inject the 0.5% acidic and 1% acidic pastes was less than the acidic/neutral paste used as a control (control 167.7 ± 85.6; 0.5% acidic 41.3 ± 10.7, p = 0.070; 1% acidic 28.0 ± 7.0, p = 0.940). At 72 hours, all paste formulations exhibited in vitro activity against Staphylococcus aureus (control 2.6 ± 0.8; 0.5% acidic 98.1 ± 33.5, p = 0.002; 1% acidic 87.3 ± 17.2, p = 0.006; acidic/neutral 83.5 ± 14.3, p = 0.010) and Pseudomonas aeruginosa (control 163.0 ± 1.7; 0.5% acidic 85.7 ± 83.6, p = 0.373; 1% acidic 38.0 ± 45.1, p = 0.896; acidic/neutral 129.7 ± 78.0, p = 0.896). Also, the paste formulations were able to prevent the infection with 100% clearance on the implanted hardware and surrounding tissue with the control being a 0.5% acidic paste group without antibiotics (control 4 × 104 ± 4.8 × 104; 0.5% acidic 0.0 ± 0.0, p value: 0.050; 1% acidic 0.0 ± 0.0, p = 0.050; acidic/neutral 0.0 ± 0.0, p = 0.050). The preliminary studies demonstrated promising results for the blended chitosan/PEG pastes with antibiotics provided degradability, biocompatibility, injectability, and infection prevention for musculoskeletal-type wounds. The preliminary studies with the chitosan paste delivered antibiotics to a contaminated musculoskeletal wound with hardware and prevented infection. More studies in a complex musculoskeletal wound and dosage studies are needed for continued development.

Polymicrobial Biofilm Inhibition Effects of Acetate-Buffered Chitosan Sponge Delivery Device.

Polymicrobial biofilm-associated implant infections present a challenging clinical problem. Through modifications of lyophilized chitosan sponges, degradable drug delivery devices for antibiotic solution have been fabricated for prevention and treatment of contaminated musculoskeletal wounds. Elution of amikacin, vancomycin, or a combination of both follows a burst release pattern with vancomycin released above minimum inhibitory concentration for Staphylococcus aureus for 72 h and amikacin released above inhibitory concentrations for Pseudomonas aeruginosa for 3 h. Delivery of a vancomycin, amikacin, or a combination of both reduces biofilm formation on polytetrafluoroethylene catheters in an in vivo model of contamination. Release of dual antibiotics from sponges is more effective at preventing biofilm formation than single-loaded chitosan sponges. Treatment of pre-formed biofilm with high-dose antibiotic release from chitosan sponges shows minimal reduction after 48 h. These results demonstrate infection-preventive efficacy for antibiotic-loaded sponges, as well as the need for modifications in the development of advanced materials to enhance treatment efficacy in removing established biofilm.

Evaluation of Vacuum Assisted Closure Therapy for Soft Tissue Injury in Open Musculoskeletal Trauma.

The application of controlled levels of negative or sub atmospheric pressure for a prolonged period of time on a wound had shown to accelerate removal of excess fluid and promote hyperaemia, which eventually promote wound healing. The study was conducted with the aim to evaluate the effectiveness of Vacuum Assisted Closure (VAC) therapy for soft tissue injury in open musculoskeletal trauma. Twenty cases of complex musculoskeletal wound involving different parts of body were included in this progressive randomized study. In patients, aggressive debridement was done before the application of VAC therapy. Controlled negative pressure was uniformly applied to the wound. Dressings were changed after every 4 to 5 days. The evaluation of results included healing rate of the wound, eradication of infection, complication rate, and number of secondary procedures. VAC therapy over the wound was administered for an average of 20.4 days ±6.72 days (range 14 to 42 days). There was decrease in wound size attained by VAC therapy ranged from 2.6 to 24.4cm(2), with an average reduction of 10.55 cm(2). Three wounds were infected at the start of VAC therapy. However, all patients were cleared of bacterial infection by the end of VAC therapy. VAC therapy using negative pressure promote Wound healing by increasing local capillary perfusion and increased rate of granulation tissue formation, decreases the duration of wound healing and requires fewer painful dressing change.