Objective. In the present study, we aimed to assess whether gelatin/β-tricalcium phosphate (β-TCP) composite porous scaffolds could be used as a local controlled release system for vancomycin. We also investigated the efficiency of the scaffolds in eliminating infections and repairing osteomyelitis defects in rabbits. Methods. The gelatin scaffolds containing differing amounts of of β-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis models of rabbits were established. After thorough debridement, the osteomyelitis defects were implanted with the scaffolds. Radiographs and histological examinations were carried out to investigate the efficiency of eliminating infections and repairing bone defects. Results. The prepared gelatin/β-TCP scaffolds exhibited a homogeneously interconnected 3D porous structure. The G-TCP0 scaffold exhibited the longest duration of vancomycin release with a release duration of eight weeks. With the increase of β-TCP contents, the release duration of the β-TCP-containing composite scaffolds was decreased. The complete release of vancomycin from the G-TCP5 scaffold was achieved within three weeks. In the treatment of osteomyelitis defects in rabbits, the G-TCP3 scaffold showed the most efficacious performance in eliminating infections and repairing bone defects. Conclusions. The composite scaffolds could achieve local therapeutic drug levels over an extended duration. The G-TCP3 scaffold possessed the optimal porosity, interconnection and controlled release performance. Therefore, this scaffold could potentially be used in the treatment of chronic osteomyelitis defects. Cite this article: J. Zhou, X. G. Zhou, J. W. Wang, H. Zhou, J. Dong. Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/β-tricalcium phosphate composite scaffold. Bone Joint Res 2018;7:46–57. DOI: 10.1302/2046-3758.71.BJR-2017-0129.R2

Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

Objective

A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation.

Aims. Treatment of chronic osteomyelitis (COM) for young patients remains a challenge. Large bone deficiencies secondary to COM can be treated using induced membrane technique (IMT). However, it is unclear which type of bone graft is optimal. The goal of the study was to determine the clinical effectiveness of bone marrow concentrator modified allograft (BMCA) versus bone marrow aspirate mixed allograft (BMAA) for children with COM of long bones. Methods. Between January 2013 and December 2017, 26 young patients with COM were enrolled. Different bone grafts were applied to repair bone defects secondary to IMT procedure for infection eradication. Group BMCA was administered BMCA while Group BMAA was given BMAA. The results of this case-control study were retrospectively analyzed. Results. Patient infection in both groups was eradicated after IMT surgery. As for reconstruction surgery, no substantial changes in the operative period (p = 0.852), intraoperative blood loss (p = 0.573), or length of hospital stay (p = 0.362) were found between the two groups. All patients were monitored for 12 to 60 months. The median time to bone healing was 4.0 months (interquartile range (IQR) 3.0 to 5.0; range 3 to 7) and 5.0 months (IQR 4.0 to 7.0; range 3 to 10) in Groups BMCA and BMAA, respectively. The time to heal in Group BMCA versus Group BMAA was substantially lower (p = 0.024). Conclusion. IMT with BMCA or BMAA may attain healing in large bone defects secondary to COM in children. The bone healing time was significantly shorter for BMCA, indicating that this could be considered as a new strategy for bone defect after COM treatment. Cite this article: Bone Joint Res 2021;10(1):31–40

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution. Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection. We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well

Treatment of tibial osteomyelitis can be challenging and lengthy, with numerous complications possible during rehabilitation. We report on the usage of the Taylor Spatial Frame (TSF) for a large cohort of patients, and analyse factors that affect outcomes. Between 2015-2020, 51 patients were treated with TSF for osteomyelitis at a major trauma centre. Demographic, infection and treatment factors of: age, smoking status, diabetes, and BMI, acute (<6 weeks post injury) or chronic (>6 weeks) osteomyelitis, bacteria isolated, time to debridement, therapy/surgery number of TSF, time TSF was in, antibiotic treatment period, time to partial weight bear (PWB) and full weight bear (FWB) prescriptions, were collected. Outcomes of complications and time to union were obtained. Radiological union was achieved at mean 11.0 months. Mean follow up was 24.1 months. Six and three patients were further treated with fusion and amputation respectively. Mean treatment time with TSF was 12.1 months. 78% had some complications, with pin site infection, malunion, and non-union being most prevalent. Univariate factor analysis, multicollinearity diagnostics, then multivariate model construction were performed. Staphylococcus Epidermidis in bone debridement microbiology was significantly negatively associated with pin site infection (OR 0.093, 95% CI 0.011-0.828) and malunion (OR 0.698, 95% CI 0.573-0.849), and enterococcus with non-union (OR 0.775, 95% CI 0.656-0.916), during the treatment period. Time to union was significantly positively associated with time from admission to debridement (p=0.035), time TSF was in (p=0.021), presence of complications (p=0.045), bone loss complication(p=0.037), time to FWB prescription(p=0.001). We have analysed the effectiveness of TSF in the treatment of tibial osteomyelitis, and elucidated important injury, treatment and rehabilitation factors that affect outcome. The negative bacterial-complication cross associations could be due to successful eradication as culture specific antibiotics were used postoperatively. Earlier patient full weight bearing could enhance callous formation leading to faster union

Aims. This study was designed to characterize the recurrence incidence and risk factors of antibiotic-loaded cement spacer (ALCS) for definitive bone defect treatment in limb osteomyelitis. Methods. We included adult patients with limb osteomyelitis who received debridement and ALCS insertion into the bone defect as definitive management between 2013 and 2020 in our clinical centre. The follow-up time was at least two years. Data on patients’ demographics, clinical characteristics, and infection recurrence were retrospectively collected and analyzed. Results. In total, 314 patients with a mean age of 52.1 years (SD 12.1) were enrolled. After a mean of 50 months’ (24 to 96) follow-up, 53 (16.9%) patients had infection recurrence including 32 tibiae, ten femora, ten calcanea, and one humerus. Of all patients with recurrence, 30 (9.6%) occurred within one year and 39 (12.4%) within two years. Among them, 41 patients needed reoperation, five received antibiotics treatment only, and seven ultimately required amputations. Following multivariable analysis, we found that patients infected with Gram-negative bacilli were more likely to have a recurrence (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.20 to 6.94; p = 0.046) compared to Staphylococcus aureus; segmental bone defects (OR 5.25, 95% CI 1.80 to 15.26; p = 0.002) and smoking (OR 3.00, 95% CI 1.39 to 6.50; p = 0.005) were also independent risk factors for recurrence after treatment. Conclusion. Permanent ALCS might be an alternative strategy for definitive bone defect management in selected osteomyelitis cases. However, the overall high recurrence found suggests that it should be cautiously treated. Additionally, segmental defects, Gram-negative infections, and smoking were associated with an increased risk of infection recurrence. Cite this article: Bone Joint Res 2023;12(8):467–475

Aim. Osteomyelitis is a difficult-to-treat disease with high chronification rates. The surgical amputation of the afflicted limb sometimes remains as the patients’ last resort. Several studies suggest an increase in mitochondrial fission as a possible contributor to the accumulation of intracellular reactive oxygen species and thereby to cell death of infectious bone cells. The aim of this study is to analyze the ultrastructural impact of bacterial infection and its accompanying microenvironmental tissue hypoxia on osteocytic and osteoblastic mitochondria. Method. 19 Human bone tissue samples from patients with osteomyelitis were visualized via light microscopy and transmission electron microscopy. Osteoblasts, osteocytes and their respective mitochondria were histomorphometrically analyzed. The results were compared to the control group of 5 non-infectious human bone tissue samples. Results. The results depicted swollen hydropic mitochondria including depleted cristae and a decrease in matrix density in the infectious samples as a common finding in both cell types. Furthermore, perinuclear clustering of mitochondria could also be observed regularly. Additionally, increases in relative mitochondrial area and number could be found as a sign for increased mitochondrial fission. Conclusions. The results show that mitochondrial morphology is altered during osteomyelitis in a comparable way to mitochondria from hypoxic tissues. This suggests that manipulation of mitochondrial dynamics in a way of inhibiting mitochondrial fission may improve bone cell survival and exploit bone cells regenerative potential to aid in the treatment of osteomyelitis

Aim. This study assessed quality of life (QoL) in patients having external fixation for treatment of osteomyelitis and fracture-related infection (OM/FRI). Method. Patients who had surgery for OM/FRI and who completed the EuroQoL EQ-5D-5L or EQ-5D- 3L questionnaires, were identified between 2010 and 2020. Patients were followed-up for 2 years after surgery. QoL was compared between patients who had either an Ilizarov frame or a monolateral external fixator with those who did not receive external fixation. Results. 165 patients were included. Of these, 37 (22.4%) underwent application of external fixation which included 23 circular frames and 14 monolateral external fixators. Patients in the frame group had more BACH ‘Complex’ infections (34/37; 91.9%), compared to non-frame patients (57/81; 70.3%). Pre-operatively, the mean EQ-index score for patients planned to receive a frame (0.278 SD 0.427) was worse compared to other treatments (0.453 SD 0.338, p=0.083). At 6 weeks after surgery, the EQ-index score remained significantly lower in frame patients compared to non-frame patients (frame: 0.379 SD 0.363; no frame: 0.608 SD 0.326, p=0.016). By 6 months, 26/37 patients had undergone frame removal. The patients who had frames in situ at 6 months had lower EQ-index scores when compared to patients who had their frames removed (frame in situ: 0.187 SD 0.213; frame removed 0.674 SD 0.206, p=0.076). At one year, 36/37 (97.3%) patients had their frame removed. QoL had greatly improved, to levels similar to non-frame patients (no frame: 0.652 SD 0.357; frame removed: 0.657 SD 0.247, p=0.949). Conclusions. Frame treatment leads to significant improvement in Quality of Life in patients suffering from osteomyelitis, with similar results in EQ5D scores after 1 year compared to patients who did not need an external fixator. These effects cannot be felt until after the frame has been removed with impaired QoL during frame treatment, especially in those patients with frames in situ for more than 6 months. This underlines the need for close and professional patient support during frame treatment for bone infection

Aim. Patient quality of life (QoL) in untreated bone infection was compared to other chronic conditions and stratified by disease severity. Method. Patients referred for treatment of osteomyelitis (including fracture related infection) were identified prospectively between 2019 and 2023. Patients with confirmed infection completed the EuroQol EQ-5D-5L questionnaire. Clinicians blinded to EQ-index score, grouped patients according to JS-BACH Classification into ‘Uncomplicated’, ‘Complex’ or ‘Limited treatment options’. A systematic review of the literature was performed of other conditions that have been stratified using EQ-index score. Results. 257 patients were referred, and 219 had suspected osteomyelitis. 196 patients had long bone infection and reported an average EQ-index score of 0.455 (SD 0.343). 23 patients with pelvic osteomyelitis had an average EQ-index score of 0.098 (SD 0.308). Compared to other chronic conditions, patients with long-bone osteomyelitis had worse QoL when compared to different types of malignancy (including bladder, oropharyngeal, colorectal, thyroid and myeloma), cardiorespiratory disease (including asthma, COPD and ischaemic heart disease), psychiatric conditions (including depression, pain and anxiety), endocrine disorders (including diabetes mellitus), neurological conditions (including Parkinson's disease, chronic pain and radiculopathy) and musculoskeletal conditions (including osteogenesis imperfecta, fibrous dysplasia and x-linked hypophosphataemic rickets). QoL in long-bone infection was similar to conditions such as Prada-Willi syndrome, Crohn's disease and juvenile idiopathic arthritis. Patients who had a history of stroke or multiple sclerosis reported worse QoL scores compared to long-bone infection. Patients who had pelvic osteomyelitis gave significantly lower QoL scores when compared to all other conditions that were available for comparison in the literature. In long bone infection, 41 cases (21.0%) were classified as ‘Uncomplicated’, 136 (69.4%) as ‘Complex’ and 19 (9.7%) as ‘Limited treatment options available’. Within classification stratification, patients with ‘Uncomplicated’ long bone infections reported a mean EQ-index score of 0.618 (SD 0.227) which was significantly higher compared to ‘Complex’ (EQ-index: 0.410 SD 0.359, p=0.004) and ‘Limited treatment options available’ (EQ-index: 0.400 SD 0.346, p=0.007). Conclusions. Bone and joint infections have a significant impact on patient quality of life. It is much worse when compared to other common chronic conditions, including malignancy, cardiovascular and neurological diseases. This has not been previously reported but may focus attention on the need for more investment in this patient group

Aim. The use of bone substitutes such as calcium sulfate (CaSO4) and hydroxyapatite with local antibiotics are crucial in the treatment of osteomyelitis. They allow the treatment of the dead space and locally provide large concentrations of antibiotics. However, it is unknown whether use of local vancomycin may elute and influence on vancomycin plasma levels. The aim of this study is to assess whether the addition of vancomycin to CaSO4 with hydroxyapatite may increase vancomycin plasma concentrations in in patients with osteomyelitis and therefore alter dosage adjustments. Method. The present study investigates the vancomycin plasma concentrations at 72–94 h post-surgery after the application of local vancomycin within CaSO4 (660mg vancomycin/10cc) and hydroxyapatite bone substitute in patients treated with empiric intravenous vancomycin and surgically treated for osteomyelitis. Vancomycin plasma concentrations were analyzed in twelve patients with osteomyelitis surgically treated with local release of vancomycin by CaSO4 and hydroxyapatite and undergoing therapeutic drug monitoring (TDM) of their vancomycin plasma concentrations as it is routinely done in our hospital. From 2019 to 2022, demographic data, microbiology, type of osteomyelitis, amount of local vancomycin applied, alteration of renal function, and vancomycin levels were retrospectively analyzed. Results. Twelve patients were included: 9(75%) were men. Median (range) demographic and clinical data: age: 51(26–67) years; body mass index: 27.7(18–46.4) kg/m2;baseline serum creatinine: 0.85 (0.7–1.24)mg/dl and 5(41.7%) with and glomerular filtration rate < 90ml/min(CPD-EPI, ml/min). Most frequently isolated microorganisms were Staphylococci (58%). Seven (54%) patients were classified as Cierny-Mader Osteomyelitis type III, 3(23%) as type IV and 2(23%) as type I. Treatment data: initial dose of vancomycin: 1g/8h in 9(75.0%) and 1g/12h in 3(25%) patients, total daily dose/body weight: 35.3(15.9–46.2) mg/kg. Pharmacokinetic data:days of iv vancomycin treatment until first TDM measurement: 3(3–4) days; minimum and maximum vancomycin plasma concentrations: 9.4(3–17.3) mg/L and 19.6(11.3–33.4) mg/L, respectively; patients with therapeutic concentrations: 6(50%); infratherapeutic: 4(33.3%) and supratherapeutic/potentially toxic: 2(16.7%). These 2 patients were young, had a baseline conserved renal function and were receiving the higher dose of 1g/8h. Conclusions. Vancomycin incorporated into the bone substitute appears not to increase blood concentrations of the glycopeptide in patients with osteomyelitis treated surgically and with intravenous vancomycin. However, 2 of the 12 patients presented supratherapeutic and potentially nephrotoxic vancomycin concentrations in the first TDM measurement, even though they were young and without renal impairment and needed and unexpected dose reduction. These results suggest the need to confirm the safety of local vancomycin in further larger clinical studies

Aim. To compare pre-referral microbiology and previous bone excision in long bone osteomyelitis with intra-operative microbiology from a specialist centre. Method. A prospective observational cohort study of patients referred to a single tertiary centre who met the following criteria: (i) aged ≥18 years, (ii) received surgery for long bone osteomyelitis and (iii) met diagnostic criteria for long bone osteomyelitis. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated. Results. 79 patients met inclusion criteria during the study period. From these, 39 (49.4%) patients had information available at referral regarding microbiology obtained from either sinus swab (n=16), bone biopsy (n=11), previous osteomyelitis excision sampling (n=7), aspiration (n=4) or blood culture (n=1). From these 39 patients, microbiology information at referral fully matched microbiology samples taken at operation in 8 cases (20.5%). Fifteen of the 39 patients (38.5%) had a different species isolated at surgery compared to referral microbiology. The remaining 16 patients (41.0%) had a culture-negative osteomyelitis on surgical sampling. Based on the microbiology obtained in our centre, 35 patients were classified as A1 (44.3%), 15 as A2 (18.9%) and 29 as culture negative, Ax (36.7%). Patients who had received previous excision of osteomyelitis before referral (n=32, 40.5%) had an increased odds ratio (OR) of having microbiology with limited antimicrobial options compared to those undergoing primary osteomyelitis excision (OR: 3.8, 95% CI 1.2 – 11.2, P=0.023, Fisher's exact test). Conclusions. Patients are frequently referred with limited microbiological information. Pre-referral microbiology in long bone osteomyelitis correlated with intra-operative samples taken at our centre in less than one quarter of cases. Pre-referral microbiology data should be used with caution for planning treatment in osteomyelitis. Previous surgery for osteomyelitis was associated with microbiology culture with limited antimicrobial treatment options

Fracture related infection, in particular chronic osteomyelitis, requires complex management plans. Meta analyses and systematic reviews have not found a gold standard of treatment for this disease. In 2017 an alternative treatment protocol was undertaken in our institution; whereby staged surgery with the use of cheaply manufactured tailored antibiotic cement rods was used in the treatment of chronic osteomyelitis, secondary to traumatic long bone fractures. Short term outcomes for this protocol demonstrated a 75.7% microbiological resolution to a negative culture and a good clinical outcome of 84.2% overall was demonstrated in terms of sinus resolution, skin changes, pain and function. Our aim now was to assess the long term outcomes of this treatment strategy. A cross-sectional study of patients who had previously undergone the set treatment protocol was performed. Patient satisfaction, effects on activities of daily living, return to work and clinical improvement at 5 years following the intervention were assessed using a patient questionnaire and the validated AAOS lower limb score. The average AAOS lower limb score was 88 which was en par to other similar studies. 80% of patients had returned to some form of work. Ongoing mild pain was a persistent problem for 50% of the patients however 98% of the patients were overall satisfied with the treatment satisfaction at 5 years. Only 1 patient required further treatment. 8 patients could not be located for follow up. Chronic osteomyelitis remains a complex disease to treat. This treatment protocol demonstrates favourable microbiological, serological and clinical short term outcomes and favourable patient satisfaction and functional long term outcomes at 5 years. Our study highlights antibiotic targeted cement rods as a feasible treatment option in managing chronic osteomyelitis

The bone infection osteomyelitis (typically Staphylococcus aureus) requires a multistep treatment process including: surgical debridement, long-term systemic high-dose antibiotics, and often bone grafting. With antibiotic resistance becoming increasingly concerning, alternative approaches are urgently needed. Herein, we develop a one-step treatment for osteomyelitis that combines local, controlled release of non-antibiotic antibacterials (copper) within a proven regenerative scaffold. To maximise efficacy we utilised bioactive glass – an established material with immense osteogenic capacity – as a copper ion delivery reservoir. Copper ions have also been shown to stimulate angiogenesis and induce MSC differentiation down an osteogenic lineage. To eliminate grafting requirements, the copper-doped BG was incorporated into our previously developed collagen scaffolds to produce multifunctional antibacterial, osteogenic, and angiogenic scaffolds. Scaffolds were fabricated by freeze-drying a co-suspension of collagen and bioactive glass particles (+/− copper doping, referred to as CuBG and BG, respectively) at a range of different concentrations (0–300% w/w bioactive glass/collagen). Scaffolds demonstrated a 2.7-fold increase in compressive modulus (300% CuBG vs. 0%; p≤0.01), whilst maintaining >98% porosity. The 300% CuBG scaffolds showed significant antibacterial activity against Staphylococcus aureus (p≤0.001). In terms of osteogenesis, both 100% and 300% CuBG scaffolds increased cell-mediated calcium deposition on the scaffolds at day 14 and 28 (p≤0.05 and p≤0.001), as confirmed by alizarin red staining. 100% CuBG scaffolds significantly enhanced angiogenesis by increased tubule formation (p≤0.01) and VEGF protein production (p≤0.001) (all ≥n=3). In summary, this single-stage, off-the-shelf treatment for osteomyelitis shows potential to minimise bone grafting and antibiotic dependence, while reducing hospital stays and costs

Introduction and Objective. Management of bone loss associated with bone contamination or infection represents a double biological and clinical challenge frequent in traumatology. The advent of new biomaterials can allow a different approach in the treatment of bone gap. The purpose of this study was to evaluate the prophylactic and therapeutic effectiveness of addition of a new absorbable bone substitute (BS) eluting different antibiotics in reconstruction of bone defects after infections and fractures with soft tissue damage. Materials and Methods. We conducted a review of patients with contaminated or infected bone defects treated using a new biomaterial, a porous composite of collagen matrices and Beta tricalcium phosphate (β TCP), able to provide a long-term release of different antibiotics. We have included treatment of osteomyelitis and osteosynthesis of exposed fracture (Gustilo Anderson 1–3b) or fractures with soft tissue damage and high risk of contamination. Surgical technique included debridement filling bone defect with BS eluting antibiotics, osteosynthesis (plate, nail, external fixator, kirschner wire), soft tissue coverage, and systemic antibiotic therapy. Radiographic and clinical data including complications (wound dehiscence, superficial or deep infection, osteomyelitis) were collected. Results. We treated 25 patients (21 male, 4 female) with mean age 47 yrs. (range 21–83). The locations treated (for incidence) was: 9 femurs (7 plates, 2 nail), 7 calcanei (one bilateral), 3 tibias, 2 forearms, 2 metatarsi, 2 hands, 1 elbow. 6 patients had large bone loss. 7 patients had bone infections (4 were Cierny Madern 4); 8 patients had osteosynthesis of exposed fractures Gustilo Anderson 1–3b (9 plate, one bilateral calcaneus). 8 patients had treatment for pseudoarthrosis of exposed fractures (6 femurs, 1 forearm, 1 metatarsus) and 3 patients a prophylactic treatment for calcaneal fractures with soft tissue damage. 4 deep infection were treated with multiple surgical debridement and new filling bone defect with BS eluting antibiotic with infection eradication. We have used a combination of vancomycin and gentamicin on 15 cases, vancomycin alone on 4 cases, combination of vancomycin and amikacin on 1 case and amikacin and Linezolid in a targeted multi drug resistance. At final follow-up functional outcome was good in all cases with bone healing. Conclusions. Extensive debridement is a fundamental requisite for eradication of bone infections and contamination. Filling of the bone void with loaded bio-composite eluting diversifiable local antibiotics with synergistic anti-biofilm activity is desirable. Treatment of this bone defects are advantaged when combining his reconstruction with BS and the possibility of release high antibiotic concentration at least for 10 days. This is an important complementing prophylactic and therapeutic antimicrobial option with adjuvant role to systemic therapy that enlarges the success rate

Background. Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below knee amputation; particularly in cases of severe soft tissue destruction. Aim. Assess the outcomes of combined ortho-plastics treatment of complex calcaneal osteomyelitis. Method. A retrospective review was performed of all patients who underwent combined single stage ortho-plastics treatment of calcaneal osteomyelitis (2008–2022). Primary outcome measures were osteomyelitis recurrence and BKA. Secondary outcome measures included flap failure, operative time, complications, length of stay. Results. 33 patients (16 female, 17 male, mean age = 54.4 years) underwent combined ortho-plastics surgical treatment for BACH “complex” calcaneal osteomyelitis with a median follow-up of 31 months (s.d. 24.3). 20 received a local flap, 13 received a free flap. Fracture-related infection (39%) and diabetic ulceration (33%) were the commonest causes. 54% of patients had already undergone at least one operation elsewhere. There were seven cases of recurrent osteomyelitis (21%); all in the local flap group. One patient required a BKA (3%). Recurrence was associated with increased mortality risk (OR 18.8 (95% CI 1.5–227.8), p=0.004) and reduced likelihood of walking independently (OR 0.14 (95% CI 0.02–0.86), p=0.042). Local flap reconstruction (OR 15 (95% CI 0.8–289.6), p=0.027) and peripheral vascular disease (OR 39.7 (95% CI 1.7–905.6), p=0.006) were associated with increased recurrence risk. Free flap reconstruction took significantly longer intra-operatively than local flaps (443 vs 174 minutes, p<0.001), but without significant differences in length of stay or frequency of out-patient appointments. Conclusions. Single stage ortho-plastic management was associated with 79% eradication of infection and 3% amputation in this complex and co-morbid patient group. Risk factors for failure were peripheral vascular disease and local flap reconstruction. Whilst good outcomes can be achieved, this treatment requires high levels of in-patient and out-patient care

Aim. Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below knee amputation; particularly in cases of severe soft tissue destruction. This study assesses the outcomes of combined ortho-plastics treatment of complex calcaneal osteomyelitis. Method. A retrospective review was performed of all patients who underwent combined single stage ortho-plastics treatment of calcaneal osteomyelitis (2008- 2022). Primary outcome measures were osteomyelitis recurrence and BKA. Secondary outcome measures included flap failure, operative time, complications, length of stay. Results. 33 patients (16 female, 17 male, mean age = 54.4 years) underwent combined ortho-plastics surgical treatment for BACH “complex” calcaneal osteomyelitis with a median follow-up of 31 months (s.d. 24.3). 20 received a local flap, 13 received a free flap. Fracture-related infection (39%) and diabetic ulceration (33%) were the commonest causes. 54% of patients had already undergone at least one operation elsewhere. There were seven cases of recurrent osteomyelitis (21%); all in the local flap group. One patient required a BKA (3%). Recurrence was associated with increased mortality risk (OR 18.8 (95% CI 1.5–227.8), p=0.004) and reduced likelihood of walking independently (OR 0.14 (95% CI 0.02–0.86), p=0.042). Local flap reconstruction (OR 15 (95% CI 0.8–289.6), p=0.027) and peripheral vascular disease (OR 39.7 (95% CI 1.7–905.6), p=0.006) were associated with increased recurrence risk. Free flap reconstruction took significantly longer intra-operatively than local flaps (443 vs 174 minutes, p<0.001), but without significant differences in length of stay or frequency of out-patient appointments. Conclusions. Single stage ortho-plastic management was associated with 79% eradication of infection and 3% amputation in this complex and co-morbid patient group. Risk factors for failure were peripheral vascular disease and local flap reconstruction. Whilst good outcomes can be achieved, this treatment requires high levels of in-patient and out-patient care

Aim. To report outcomes of soft tissue reconstruction using free tissue transfer for the treatment of tibial osteomyelitis as part of a single-stage, ortho-plastic procedure. Method. Patients who underwent ortho-plastic reconstructive surgery to excise tibial osteomyelitis in combination with free tissue transfer in one stage were included. Patients underwent surgery between 2015 and 2024 in a single specialist centre within the UK. Baseline patient information, demographics, and infection information was recorded. Adverse outcomes were defined as (i) flap salvage required, (ii) flap failure and (iii) recurrence of infection. Patient reported quality of life was measured using the EuroQol EQ-5D-5L index score. Pre-operative QoL was compared to QoL at 1 year with a control group of 53 similar patients who underwent surgical treatment for tibial osteomyelitis without a free flap (local flap or primary closure). Results. Ninety-three patients were eligible for inclusion, with a mean age of 52 years (range 18–90). 77/93 (82.8%) had a free muscle flap with the remainder (17.2%) receiving a fasciocutaneous flap. The donor tissue was defined as 57 gracilis, 6 latissimus dorsi, 14 hemi-latissimus dorsi, and 16 anterolateral thigh. The recipient area of the tibia was distal 1/3 in 52 cases, middle 1/3 in 27 cases and proximal 1/3 in 12 cases. The average flap ischaemic time was 70 minutes (range 28 to 125). Seven patients (7.5%) required urgent flap salvage at a median time of 1.0 day (range 0.5 – 4.0). Of these, 4 (4.3%) went on to have total flap failure, of which 2 patients underwent below knee amputation subsequently. Flap failure was due to either arterial (n=2) or venous (n=2) anastomotic thrombus. There were 3 (3.2%) episodes of confirmed infection recurrence within the first year after the index procedure. EQ-index scores at 1-year post-operatively were significantly improved when compared to pre-operative scores (p=0.008). At 1-year post-operatively, EQ-index scores in patients who underwent free flap was similar compared to local flaps (p=0.410) and in those who underwent primary closure for tibial osteomyelitis (p=0.070). Conclusions. Microsurgical single stage surgery can achieve high flap survival rate (95.7%). Free flaps fail early due to anastomotic thrombus with no late failures seen. Free tissue transfer does not appear to give inferior QoL compared to matched patients with local flaps or direct closure in tibial osteomyelitis

Osteomyelitis is an infection of bone or bone marrow with a concomitant inflammation involving the bone marrow and the surrounding tissues. Chronic osteomyelitis is historically treated in a two-stage fashion with antibiotic-loaded polymethylmethacrylate as local antibacterial therapy. Two-stage surgeries are associated with high morbidity, long hospitalization and high treatment costs. Next to antibiotic releasing biomaterials, S53P4 bioactive glass is a biomaterial that enables one-stage surgery in local treatment of chronic osteomyelitis. S53P4 bioactive glass is gaining interests in recent years in clinical treatment of chronic osteomyelitis in a one-stage fashion due to its antibacterial and bone regenerating capacities. By changing local pH and osmotic pressure S53P4 bioactive glass attack bacteria in a different way as compared to antibiotics. In this presentation, we will present current clinical treatment options for osteomyelitis, clinical results and level of evidence of various biomaterials used in osteomyelitis treatment. In addition, the clinical results and health-economic results of S53P4 bioactive glass will be detailed. Thereafter a summary of the current standing across the board in osteomyelitis treatment will be provided

Aim. Several local antibiotic-eluting drug delivery systems have been developed to treat bacterial bone infections. However, available systems have significant shortcomings, including suboptimal drug-release profiles with a burst followed by subtherapeutic release, which may lead to treatment failure and selection for drug resistance. Here, we present a novel injectable, biocompatible, in situ-forming depot, termed CarboCells, which can be fine-tuned for the desired antibiotic-release profile. The CarboCell technology has flexible injection properties that allow surgeons to accurately place antibiotic-eluting depots within and surrounding infectious sites in soft tissue and bones. The CarboCell technology is furthermore compatible with clinical image-guided injection technologies. These studies aimed to determine the therapeutic potential of CarboCell formulations for treatment of implant-associated osteomyelitis by mono- and dual antimicrobial therapy. Methods. The solubility and stability of several antibiotics were determined in various CarboCell formulations, and in vitro drug release was characterized. Lead candidates for antimicrobial therapy were selected using a modified semi-solid biofilm model with 4-day-matured Staphylococcus aureus biofilm (osteomyelitis-isolate, strain S54F9). Efficacy was investigated in a rat implant-associated osteomyelitis model established in the femoral bone by intraosseous implantation of a stainless-steel pin with 4-day-old in vitro-matured S. aureus biofilm. CarboCells were injected subcutaneously at the femur, and antimicrobial efficacy was evaluated 7 days post-implantation. Lead formulations were subsequently tested in a well-established translational implant-associated tibial S. aureus osteomyelitis pig model. Infection was established for 7 days before revision surgery consisting of debridement, washing, implantation of a new stainless-steel pin, and injection of antibiotic-releasing CarboCells into the debrided cavity and in the surrounding bone- and soft-tissue. Seven days post-revision, pigs were euthanized, and samples were collected for microbial and histopathological evaluation. Results. Lead antimicrobial agents were soluble in high concentrations and were stable in CarboCell formulations. Three combinations completely eradicated bacteria in the in vitro semi-solid biofilm model. In the rat osteomyelitis model, CarboCell formulations of the lead combinations also eradicated bacteria in bone and implant in several rats and significantly reduced infection in all treated rats. In the pig model, CarboCell antimicrobial monotherapy demonstrated promising therapeutic efficacy, including complete eradication of infection in bone and implants in several pigs and significantly reduced bacterial burden in others. Conclusions. Using the CarboCell technology for antimicrobial delivery exert substantial loco-regional efficacy. The attractive sustained high-dose antibiotic release profile combined with the flexible injection technology allows surgeons to accurately place effective drug-eluting depots in key areas not accessible to competing technologies