Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

Aim. Megaprosthesis have become a standard option in limb preserving surgery after bone resection in musculoskeletal tumors. Recently they have also been used in complex revision arthroplasty in cases with massive bone loss. The aim of this study was to analyze the incidence of periprosthetic joint infection (PJI) both in primary oncology cases and aseptic revision cases and analyze which are the significant risk factors for PJI with a special interest on the use of prophylactic antibiotic loaded calcium sulfate beads. Method. All patients undergoing surgery with the use of megaprosthesis in our institution between January/2012 and December/2022 were retrospectively reviewed. Data was collected from electronic medical records. We identified 108 procedures involving megaprosthesis in 90 patients with an average follow-up of 37 months. Indications were 79 primary musculoskeletal tumors and 29 aseptic complex revision arthroplasty. Results. Table 1 shows relevant clinical information. No significant risk factor was found either in uni or multivariate analysis. PJI rate was 15% (12/79) for primary musculoskeletal surgery and 31% (9/29) for complex revision surgery. The use of antibiotic loaded calcium sulfate beads did not show an advantage – 22% (9/41) with vs. 18% (12/67) without. Conclusions. In this relatively small series it was not possible to show a significal association between PJI and certain known risk factors such as gender, ASA score, site of surgery (knee) and revision surgery. The use of antibiotic loaded calcium sulfate beads as prophylaxis was not beneficial in reducing PJI rates in our cohort. We acknowledge the limitations of our study: a small sample group, in a single institution with heterogeneity in terms of diagnosis and surgical site. We recognize the need for a multicentric study with a larger cohort to validate these findings. For any tables or figures, please contact the authors directly

Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on bone regeneration when BMP-2 and zoledronic acid (ZA) were co-delivered based on a calcium sulphate/hydroxyapatite (CaS/HA) scaffold in a rat critical-size femoral defect model. Therefore, the aim of this study was to evaluate whether local application of BMP-2 and ZA released from a CaS/HA scaffold is favorable for spinal fusion. We hypothesized that CaS/HA mediated controlled co-delivery of rhBMP-2 and ZA could show an improved effect in spinal fusion over BMP-2 alone. 120, 8-week-old male Wistar rats (protocol no. 25-5131/474/38) were randomly divided into six groups in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA). A posterolateral spinal fusion at L4 to L5 was performed bilaterally by implanting group-dependent scaffolds. At 3 weeks and 6 weeks, 10 animals per group were euthanized for µCT, histological staining, or mechanical testing. µCT and histological results showed that the CaS/HA + BMP-2 + local ZA group significantly promoted bone regeneration than other treated groups. Biomechanical testing showed breaking force in CaS/HA + BMP + local ZA group was significantly higher than other groups at 6 weeks. In conclusion, the CaS/HA-based biomaterial functionalized with bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant spinal fusion outcome

Acknowledgements: Many thanks to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology).

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

Aims

The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

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.

Aim. Multispecies biofilms are associated with difficult periprosthetic joint infections (PJI), particularly if they have different antibiotic sensitivities. We aimed to determine if we could generate and kill a multispecies biofilm consisting of a Gram negative and Gram positive pathogen in-vitro with antibiotic loaded calcium sulfate beads containing single or combination antibiotics. Methods. To establish whether we could co-culture mixed species biofilms various combinations of Pseudomonas aeruginosa (PA), Enterococcus faecalis (EF), Staphylococcus aureus (SA) and Enterobacter faecalis (EF) were grown together on 316L stainless steel coupons and agar plates. Based on this screen we focused on PA + EF and challenged them with high purity calcium sulfate beads (Stimulan Rapid Cure) loaded with vancomycin (V), alone tobramycin (T) alone or vancomycin and tobramycin in combination (V+T). Bioluminescence, light imaging, plate count, confocal microscopy and scanning electron microscopy were used to quantify growth. Results. On 316LSS the V loaded bead reduced both EF and PA by approximately 2 logs compared to unloaded control beads. A T alone loaded bead eliminated PA from the dual species biofilm and caused a 2-log reduction in EF. The V+T-beads reduced PA by 9-logs and EF by 8.3 logs. In terms of total CFUs V+T beads reduced the bioburden by 8.4 logs compared to V or T alone. which resulted in 2.1 and 2.6 log reductions respectively. (* P<0.05, *** P<0.001). On agar PA dominated the culture for the unloaded and V loaded beads. However, when challenged with a T loaded bead both species were able to coexist and a zone of killing was generated in both species in the multispecies biofilms. However, this zone was smaller and included more tolerant variants than the zone generated by V+T-loaded beads. Conclusions. There were species proportion differences between biofilms grown on agar and 316LSS demonstrating the importance of growth conditions on species interactions. Antibiotics against strains with differing sensitivities can shift species interactions. High purity calcium sulfate beads containing tobramycin a broad-spectrum Gram positive and negative antibiotic vancomycin, a Gram-positive targeted antibiotic killed a larger percentage of a multispecies in an in-vitro biofilm than either single gram-specific antibiotic alone, demonstrating the advantage of using combination antibiotics for treating multispecies biofilms

Introduction. Cerament, a bioresorbable hydroxyapatite and calcium sulfate cement, is known to be used as a bone-graft substitute in traumatic bone defect cases. However, its use in open fractures has not previously been studied. Materials and Methods. Retrospective, single-centre review of cases between November 2016 and February 2021. Open fractures were categorised according to the Orthopaedic Trauma Society classification (OTS). Cases were assessed for union, time to union, and associated post-operative complications. Results. Twenty-four patients were identified. Fifteen cases were classified as OTS simple open fractures, and nine cases were complex open fractures requiring soft tissue reconstruction. Four cases were lost to follow-up. Four cases had limited follow-up beyond 6 months but showed evidence of progressive radiographic union. Of the remaining 16 cases, eight cases (50%) went on to union with a mean time to union of 6.7 months (5 to 12 months). Persistent non-union remained in six cases (38%). Two cases required return to theatre due to an infected skin graft and wound dehiscence respectively. One case had the complication of persistent weeping of Cerament from the wound. This self-resolved within two weeks. Limitations of this case series include the lack of complete follow-up in eight patients (33%) and the lack of patient reported outcome measures. Conclusions. Cerament can be a useful adjunct in managing open fractures. However, it should be noted there is a high rate of non-union which may be reflective of the significant morbidity associated with open fractures with structural bone defects

Aims

Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients.

Purpose. Infections in orthopaedic surgery are costly, debilitating complications. The search for new treatments and prevention strategies has led to the use of antibiotic-filled calcium sulfate (CaS) as a bone void filler that is both safe and effective. The purpose of this study was to examine the available data on the efficacy of this technology. Methods. A literature search was performed for studies that evaluated the use of antibiotic-loaded CaS cement in orthopaedics published between inception of the databases to 2017. Selected studies included randomized controlled trials (RCTs) and observational studies published in the English language that met the following criteria: 1) patients underwent an orthopaedic procedure; 2) CaS cement with an antibiotic was used; and 3) at least one of our outcomes were mentioned. Outcomes included resolution of infection, complications related to treatment, subsequent surgeries, overall infection rate, fracture union rate, clinical outcomes, and wound complications. A total of 17 studies were included. Results. Ten studies examined the use of antibiotic-eluting CaS cement with surgical debridement to treat osteomyelitis and reported resolution rates ranging from 80–100%. Two studies examined CaS for prophylaxis of infection after open fracture, with subsequent infection rates ranging from 0–22%. Two studies examined infected non-unions with CaS used as an adjunct to surgery with an 87.5% infection clearance rate. Finally, three studies examined the use of local antibiotic release from CaS in the repair of infected TKAs or THAs, with success rates ranging from 52–93.3%. Conclusion. Initial results support the use of CaS with surgical debridement for osteomyelitis and infected non-unions. Results are mixed for CaS use in the prophylaxis of infection after open fractures and for PJIs, thereby necessitating further research. Overall the studies were small, retrospective, and lacked controls. Further research should focus on RCTs to minimize bias and investigate for non-inferiority. For any figures or tables, please contact authors directly

Introduction. Today, Uganda has the second highest rate of road accidents in Africa and the world after Ethiopia. According to the World Health Organization's Global Status Report on Road Safety 2013, Uganda is named among countries with alarmingly high road accident rates. If such trend of traffic accidents continues to increase, the health losses from traffic injuries may be ranked as the second to HIV/AIDS by 2020. These road traffic accidents often result in terrible open injuries. Open fractures are complex injuries of bone and soft tissue. They are orthopedic emergencies due to risk of infection secondary to contamination and compromised soft tissues and sometimes vascular supply and associated healing problems. Any wound occurring on the same limb should be suspected as result of open fracture until proven otherwise. The principles of management of open fracture are initial evaluation and exclusion of life threatening injuries, prevention of infection, healing of fracture and restoration of function to injured extremity. Because of the poor hygienic circumstances and the high rate of cross-infection due to the crowded patient-wards, the risk of getting a post-operative infection is relatively high. Osteoset-T® (Wright Medical) is a medical grade calcium sulfate bone graft substitute which is enhanced for use in infected sites by incorporating 4% tobramycin sulfate. The tobramycin is released locally, allowing therapeutic antibiotic levels at the graft site, while maintaining low systemic antibiotic levels. This local treatment of infection allows new bone formation in the defect site, while decreasing potential systemic effects. Purpose/aim. Prevention and treatment of postoperative osteomyelitis by introducing alcoholic hand-sanitizers and the use of wound debridement and implantation of a medicated bone graft substitute. Materials and Methods. We treated some existing osteomyelitis cases and some open fractures with the medicated bone graft substitutes, at Kilembe Mines Hospital, Uganda. A proper debridement with sequestrectomy when needed was performed after which the pellets were implanted and the wound was closed. A preoperative X-ray was taken as well as clinical pictures. Post-operative x-rays were obtained at 6 weeks post-operative and 6 months post-operative when possible. The case presented in this abstract is a 25year old nurse with a bilateral open tibia fracture due to a motorcycle accident. A proper debridement and plate and screw osteosynthesis was performed after which the pellets were implanted underneath the plate. After surgery systemic antibiotics were given and the wound-dressings were changed when dirty. Results. The case presented is currently 6 months post-operatively and is able to walk without support. The fracture is fully consolidated and the wounds are healed without any sign of infection. Conclusion. Even though the clinical follow-up is not easy in this developing country setting, we were able to evaluate some patients postoperatively. By introducing better hand hygiene (by use of alcoholic hand sanitizers) and medicated bone graft substitutes, we hope to be able to prevent osteomyelitis after open fractures and also to treat chronic osteomyelitis cases. More people are being treated at the moment and a case-control study will be started soon

Aim. Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin resistant Enterococci (VRE) have emerged as multi-drug resistant Gram-negative pathogens associated with Periprosthetic Joint Infections (PJI). In this study, we evaluated the efficacy of antibiotic-loaded calcium sulfate beads (ABLCB) to inhibit bacterial growth, biofilm formation and eradicate preformed biofilms of K. pneumoniae and E. faecalis. Method. Three strains of K. pneumoniae (carbapenem resistant BAA1705, New Delhi metallo-beta-lactamase producing BAA2146 [NDM-1], a carbapenemase producing BAA2524) and a vancomycin resistant strain of E. faecalis (ATCC51299) were used. 4.8mm diameter ABLCBs (Stimulan Rapid Cure, Biocomposites) were loaded with vancomycin (VAN) & gentamicin (GEN) at 500 and 240 mg/10cc pack or VAN & rifampicin (RIF) at 1000 and 600 mg/10cc pack respectively and placed onto tryptic soy agar (TSA) plates spread with each of the four strains independently and incubated for 24 hours at 37°C. The beads were transferred daily onto fresh TSA medium spread with the test cultures. The zone of inhibition was recorded until no inhibition was observed. Biofilm prevention efficacy was investigated in 6 well plates. Bacterial cells (5×10. 5. CFU/mL in tryptic soy broth) were treated with ABLCBs. Media was removed and challenged with bacteria daily for 7 days. CFU counts were taken after 1, 2, 3 and 7 days. For biofilm killing, ABLCB were added to 3 day formed biofilms in 6 well plates. CFU counts were estimated at 1, 3 and 7 days with daily media exchange. Results. ABLCB demonstrated effective initial eluting concentrations depending on the strains. The NDM-1 strain of K. pneumoniae had lower sensitivity than other strains towards VAN & RIF and resistant towards VAN & GEN. E. faecalis was sensitive to both combinations. For repeat challenges, ABLCBs prevented colonisation and reduced biofilm formation, except for the NDM-1 strain which grew in the presence of VAN & GEN. Preformed biofilms were more difficult to reduce with antibiotics than in the prevention assay. Biofilm growth was observed at 1 week of contact with ABLCBs, despite negative cultures at earlier time points for K. pneumoniae and E. faecalis. However, there was a significant killing (2–3 logs, P<0.05) of biofilm bacteria with all antibiotic combinations compared to unloaded beads. Conclusions. This study provides evidence that local release of antibiotics from ABLCBs may be useful in the treatment of multidrug resistant strains of K. pneumoniae and E. faecalis (CRE and VRE) associated with PJIs. In-vitro results do not necessarily correlate to clinical results

The combination of natural polymers with calcium phosphate cements (CPCs) by mimicking the highly mineralized collagen-based matrix of native bone is crucial in order to obtain mechanically compatible injectable bone substitute (IBS) formulations. This combination overcomes the drawbacks of CPCs like high resorbability, poor mechanical properties, and degradability. In this study, methylcellulose (MC) was combined with CPCs because of MC's thermoresponsive behavior which makes MC suitable for IBS application. In addition, gelatin (GEL) was also incorporated to adjust the gelation temperature and to enhance cell adhesion. These polymers combination makes the liquid (L) phase. The powder (P) phase comprised of tetra calcium phosphate (TTCP), dicalcium phosphate dehydrates (DCPD), and calcium sulfate dehydrates (CSD). TTCP and DCPD are commonly studied for the development of bone cements and they lead to high-density products. CSD was added to the powder phase to increase the porosity as well as to enhance mechanical properties of the IBS. TTCP was synthesized using a solid state method. Test tube inversion method was used to adjust the gelation temperature. GEL concentration was kept constant at 5 wt% and MC concentration varied between 1.5 and 12 wt%. The weight fraction of P/L phase was used as 1.8:1 (wt/wt). Synthesized IBS was characterized by using X-Ray Diffraction (XRD), Fourier Transform Infrared Analysis (FTIR), Zeta Particle Size Analysis, rheometry, and thermogravimetric analysis. XRD and FTIR analysis proved that TTCP was successfully synthesized with a particle size of 430.1 nm. The particle size of P phase mixture was measured as 581.1 nm. Based on the test tube inversion tests, weight fraction of MC was chosen as 10 and 12 while the weight fraction of GEL was fixed as 5. FTIR spectra of the liquid phase was showed that there was a hydrophilic interaction between MC and GEL since both Amide I at 1633 cm. −1. and β-gylcosides bonds among saccharide units at 900–1230 cm. −1. were clearly seen. MC10GEL5/P and MC12GEL5/P were analyzed by the XRD. According to this analysis, only the peaks of TTCP, DCPD, and CSD were observed. From the rheological data obtained from the rheometer, it is evident that all the prepared formulations exhibited Newtonian flow. The measured viscosity of all the investigated formula remained constant with the applied force over time. The MC12GEL5/P had the highest viscosity value due to its high concentration of MC (12% w/v). Results of TG of the synthesized IBS showed two main decomposition steps for the L phase because of the hydrophilic interaction between MC and GEL. The synthesized self-crosslinkable IBS represent promising platforms for future studies in bone tissue engineering. Overall, the presented study identified a novel IBS with suitable viscoelastic properties for non-invasive treatment of bone defects which may ultimately be a substitute for surgery for a wide variety of therapeutic applications

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration.

Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Aim. Infection rates after revision THA vary widely, up to 12%. In countries that use antibiotic-loaded cemented stems in combination with perioperative IV antibiotics, infection rates in registry studies are lower. In many countries, however, cementless revision implants are preferred. Our aim was to apply an antibiotic-loaded calcium sulfate coating to cementless revision stems to reduce periprosthetic joint infection (PJI). This study sought to answer two questions: 1) Does the coating of cementless revision stems with calcium sulfate inhibit osteointegration in THA? 2) Does the antibiotic-loaded calcium sulfate coating of revision stems reduce the incidence of PJI?. Method. From Dec. 2010 to Dec. 2015, 111 consecutive revision femoral stems were coated with commercially pure calcium sulfate. 10cc of calcium sulfate was mixed with 1g of vancomycin powder and 240mg of tobramycin liquid and applied to the stem in a semi-firm liquid state immediately prior to stem insertion. The results are compared to a designated control cohort (N=104) performed across the previous 5 years. The surgical methods were comparable, but for the stem coating. All patients were staged preoperatively using the Musculoskeletal Infection Society Staging System and followed for at least 1 year. Results. In the study group of coated stems, there were 46 A hosts, 56 B hosts, and 9 C hosts. In the control group, there were 45 A hosts, 52 B hosts, and 7 C hosts. Both cohorts had 0 cases of aseptic loosening. The overall rate of PJI in the study cohort was 2.7%. Of the 111 revisions, 69 were aseptic (PJI=1.4%) and 42 were second stage revisions for infection (PJI=4.8%). PJI occurred in 2.2% of A hosts, 1.8% of B hosts, and 11.1% of C hosts. In the control cohort, the overall rate of PJI was 7.7%. Of the 104 revisions, 74 were aseptic (PJI=1.4%) and 30 were second stage revisions for infection (PJI=23.3%). PJI occurred in 6.7% of A hosts, 5.8% of B hosts, and 28.6% of C hosts. The results show a reduction in PJI from 7.7% in the control group to 2.7% in the study group and were found to be statistically significant at p-value<0.1 (p=0.09). Conclusions. The application of antibiotic-loaded calcium sulfate to cementless revision femoral stems does reduce PJI. Importantly, this coating did not inhibit osteointegration of the femoral stem. The reduced infection rate in this study supports the concept that bacteria frequently contaminate and reside within the femoral canal

Aim. Bacterial biofilms play a key role in prosthetic infection (PI) pathogenesis. Establishment of the biofilm phenotype confers the bacteria with significant tolerance to systemic antibiotics and the host immune system meaning thorough debridement and prosthesis removal often remain the only possible course of treatment. Protection of the prosthesis and dead-space management may be achieved through the use of antibiotic loaded cements and beads to release high concentrations of antibiotics at the surgical site. The antibacterial and antibiofilm efficacy of these materials is poorly understood in the context of mixed species models, such as are often encountered clinically. Methods. A P. aeruginosa and S. aureus in vitro co-culture biofilm model was grown using 1/5th BHI supplemented with 20 µM hemin. The ability of beads made from a synthetic calcium sulfate (CaSO4) loaded with vancomycin, tobramycin and vancomycin & tobramycin in combination to prevent biofilm formation and kill established co-culture biofilms were assessed using viable cell counts and confocal scanning laser microscopy (CSLM) over a 7 day time course. To assay for genetic changes to the individual species as a result of their presence together within a biofilm, mutation rates were measured using fluctuation analysis following growth as planktonic and biofilm cultures, alone or in co-culture. Mutants were determined based on their ability to grow on agar plates containing an inhibitory concentration of rifampicin. Mutation rates were calculated using the Ma-Sandri-Sarkar Maximum Likelihood Estimator and 94% confidence intervals compared for significance. Results. Mixed species biofilms displayed differential sensitivity to vancomycin alone and tobramycin alone CaSO4-loaded beads relative to single species biofilms. Preliminary data suggests 10- and 100-fold increase in mutation rates of P. aeruginosa and S. aureus, respectively, when in a co-culture relative to monospecies biofilm which, while further work is needed, may directly or indirectly contribute to the differing antibiotic sensitivities observed. A broad-spectrum intervention of CaSO4-loaded vancomycin & tobramycin beads was able to prevent bacterial colonisation and attenuate P. aeruginosa and S. aureus mixed species biofilm formation for multiple days. Conclusions. Synthetic antibiotic-loaded CS beads, with a broad-spectrum antibiotic combination, have potential to reduce or eliminate mixed species biofilm formation on implant material by providing locally high concentrations over sufficient time periods to aid in the management of PIs. * Stimulan, Biocomposites Ltd

Aim. To evaluate the clinical outcome of a new absorbable, gentamycin loaded calcium sulfate/hydroxyapatite biocomposite (CERAMENT. ™. /G) as cavity filler after debridement and removal of infected metalwork in chronic osteomyelitis. Methods. We report the retrospective study of prospectively collected data from 36 patients with chronic osteomyelitis from implant infection. Treatment included a single stage protocol with removal of the metalwork, debridement augmented with application of CERAMENT. ™. /G, stabilization, culture-specific antibiotics and primary skin closure or flap. The biocomposite was used for dead space filling after resection of Cierny-Mader (C-M) stage III and IV chronic osteomyelitis. Data were collected on patient age, comorbidities, operation details, microbiology, postoperative complications and type of fixation or plastic surgery. Primary measure of outcome was recurrence rate. Results. According to the C-M classification 22 patients (63%) were defined as Type III and 13 (37%) as Type IV. A total of 26 (72%) patients were Class B hosts. In 9 cases (25%), there was an infected non-union and 1 patient had septic arthritis. Mean age was 52 years (range 22 to 81). Patients were followed for a mean of 20 months (range 6 to 36). Infection was eradicated in 32 patients. There were three (8.3%) recurrences (two cases of osteomyelitis and one of soft tissue/flap infection). Two of them were successfully managed with repeat surgery (one Class B and one Class A host) and one (Class B host) with suppressive antibiotic therapy as per patient's choice. In one infected nonunion the infection was eradicated but the nonunion persisted. Thirteen patients (36.6%) had a local or free fascio-cutaneus flap. Staphylococci (50%) and Enterococci (15%) were the most common microorganisms. Pseudomonas aeruginosa was more common in polymicrobial infection usually with Staphylococcus aureus. Conclusions. A multidisciplicary approach including augmented debridement with CERAMENT. ™. /G is effective for treatment of chronic osteomyelitis with infected metalwork

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly four types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

Objectives

This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling.