Aim. To retrospectively investigate the clinical outcome after surgical, single-stage treatment of orthopaedic infections using antibiotics delivered locally by a calcium sulphate/hydroxyapatite biocomposite. Method. In order to identify the patients, we retrospectively searched several patient associated hospital-based databases using free text search with the term “Cerament” between November 2015 and November 2018. 58 cases with confirmed osteomyelitis and in which the bone substitute loaded with Gentamicin and/or Vancomycin had been used were identified and further evaluated. Results. Mean age was 58.9 years (range: 25–89). 46 (79.3 %) patients had at least 12 months follow up. The remaining 12 patients had a mean follow up time of 10.0 months (range 7–11). Infection was eradicated in 54 patients (93.1 %). In one the patients with recurrent infection repeated surgery with addition of bone substitute loaded with fosfomycin eventually eradicated the infection. One patient died of causes not related to the infection nor the treatment. Five patients presented transient white wound drainage but no signs of infection. No other side effects were identified. Conclusions. Local administration of antibiotics and dead space management using a calcium sulphate/hydroxyapatite biocomposite. 1. in combination with single-stage surgical debridement, stabilisation and postoperative culture-specific systemic antibiotics resulted in a high amount of eradicated infections and in line with other authors

To demonstrate the role of an antibiotic containing bone substitute, native bone active proteins and muscle transforming into bone. Recurrent osteomyelitis was eradicated and filled with a gentamycin eluting bone substitute (Cerament™l G) consisting of sulphate and apatite phases and covered by a muscle flap. C2C12 muscle cells were seeded on the bone substitute in-vitro and their phenotype was studied. Another muscle cell line L6 was seeded with osteoblast conditioned medium containing bone active proteins and specific markers were studied for bone differentiation. A chronic, longstanding, fistulating osteomyelitis was operated with radical eradication and filling of the cavity with gentamycin eluting bone substitute. At one year, the patient had no leg pain and a healed wound. Significant bone was also seen in the overlaying muscle, at one month post-op disappearing after 6-months. Local delivery of gentamycin had a protective effect on bone formation. C2C12 cells seeded on the gentamycin eluting bone substitute depicted no difference in proliferation when compared to plain bone substitute and expressed 4 folds higher Alkaline phosphatase (ALP) compared to controls. C2C12 cells expressed proteins and genes coding for collagen type 1 (Col 1), osteocalcin (OCN), osteopontin (OPN) and bonesialoprotein (BSP). L6 cells cultured with osteoblast conditioned medium remained uninucleated and expressed osteoblastic proteins like Col 1, OCN, OPN and BSP. Bone substitute with gentamycin leads to differentiation of mesenchymal cells into bone in-vitro. Native bone active proteins from an osteoblast culture can induce differentiation of muscle cells in-vitro. Clinical observations with rapid bone formed in the bone substitute and in some cases in the muscle are a consequence of both leakage of bone active proteins and also from osteoprogenitor cells coming from the overlaying muscle interacting with the osteoinductive bone substitute

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. The demand for a synthetic bone substitute that can build bone and at the same time kill bacteria is high. The aim of this study was to compare the elution of gentamicin from a new synthetic bone substitute in vitro with the performance in clinical applications. Method. Gentamicin release was measured from a synthetic bone graft substitute, comparing in vitro and clinical conditions:. 1). elution in Ringers solution. The bone graft substitute contained 175mg gentamicin per 10mL. The material was introduced either as paste or as pre-set beads with a high or low surface areas, >100cm. 2. and 24cm. 2. respectively. The gentamycin release was measured by daily collection of samples. 2). elution in patients treated for trochanteric hip fractures(n=6) or uncemented hip revisions(n=5) 7,3±1,1mL of substitute was implanted and drainage was collected at 6h,12h,24h,30h,36h post-op. Blood serum was collected every hour for the first 6h and thereafter every 6h until 4 days post-op, urine – daily for the first 7 days post-op. 3). elution in patients treated after bone tumor resection(n=8), 12,1±5,5mL of substitute was implanted and both drainage and blood serum were collected daily until 2 days post-op. Gentamicin concentrations were analyzed using antibody technique. Results. In the in vitro study, there was an initial peak in the gentamicin concentration (GC) for all the samples and at a level above 4mg/L, which is the MIC break point, during the whole test period of 28 days. All gentamicin was released during the test period and more than 95 % had been released after 2–4 days independently of the surface area of the material, or if it was pre-set or paste. In the clinical studies similar results were found. Gentamicin was detected in the drainage until 2 days post-op. and the hip patients 40% less GC – compared to the tumor patients. In the blood serum with higher GC in the tumor patients and non-detectable levels after 2 days post-op for the hip patients. The GC was significantly lower than maximum systemic level recommended of 12 mg/L. In the urine, GC was above the MIC of 4mg/L for the first seven days post-op. Conclusions. A reliable in vitro test method has been identified for the future development of additional new and effective antibiotic containing bone substitutes. The new bone regenerating carrier gives very high local antibiotic release for a controlled short time after surgery and high systemic serum concentrations are avoided

Aim of this work was to evaluate the efficacy of a new antibiotic bone substitute (CERAMENTTM|G) in the treatment of osteomyelitis (OM) in diabetic foot. From June 2013 to April 2015 we used a new Calcium Sulphate Hemihydrate + Hydroxyapatite + Gentamicin Sulfate (CSH + HA + GS) compound to fill resected bone voids following surgical intervention in cases of diabetic foot OM. The uniqueness of this product is that it induces native bone growth, while the synthetic bone disappears and antibiotic is released into the surrounding tissues, maintaining high gentamicin concentrations for some weeks. In 20 patients, with or without Charcot neuroarthropathy and post-lesional osteomyelitis, after removal of infected bone we applied 10 to 20 ml CSH + HA + GS, filling the residual spaces and aiming to stabilize the remaining bone fragments. When needed, these arthrodeses were stabilized by external-internal hybrid fixators. X-ray evaluations and, when indicated, MRI evaluations were performed before and after surgical intervention, and 3 months post-op. Revascularization with percutaneous angioplasty was performed when needed. 20 patients affected by OM were treated, 4 of them having 1st metatarsal head involvement, 4 having heel involvement, 12 tarsal and hindfoot involvement. After surgical intervention all of them were treated with standard medication and pressure relief. The three 1st metatarsal OM cases healed, both in regards to infection and lesions. One of the patients is still ongoing. One of the patients with heel OM presented with a worsening of the infection and was treated by major amputation, another one presented with good soft tissue growth and, two months from the intervention, and in the absence of clinical signs of OM relapse, was treated with a sural fasciocutaneous pedicled flap; of the remaining two patients one heald and the other is still ongoing; 11 of the 12 patients who had midfoot or hindfoot partial resections healed, one patient is still ongoing. The healed patients are all wearing suitable shoes. The use of a new CSH + HA + GS bone substitute has shown to be efficacious in inducing OM healing and preserving foot structures in diabetic feet

Aim. The aim of this work was to evaluate, via foot and ankle TC scans, the outcomes of the use of a bone substitute (CERAMENT|™G) and the growth of native bone in the treatment of osteomyelitis (OM) of the diabetic foot. Method. In nine patients from July 2014 to December 2016 we used a Calcium Sulphate Hemihydrate + Hydroxyapatite + Gentamicin Sulfate (CSH + HA + GS) compound to fill resected bone voids following surgical intervention in OM diabetic foot cases. Of these nine patients, three were female and six were male and their ages were between 49 and 72 years. Four patients had hindfoot involvement and underwent partial calcanectomy. Two patients presented a rocker-bottom Charcot foot pattern III according to Sanders and Frykberg's classification and were treated with esostectomy of the symptomatic bony prominence of the midfoot. One patient presented OM of the 3°, 4° and 5° metatarsal bones. One patient underwent partial resection of the midfoot and hindfoot with arthrodesis stabilised by an internal-external hybrid fixator. One patient with a Charcot foot pattern IV-V underwent partial talectomy and calcanectomy with arthrodesis stabilised by an internal-external hybrid fixator. In all these patients - after removal of the infected bone - we applied 10 to 20 ml CSH + HA + GS filling the residual spaces with the aim of stabilising the remaining bone fragments. The uniqueness of this product is that it induces native bone growth, while the synthetic bone disappears and antibiotic is released into the surrounding tissues. In March 2018, the above nine patients underwent foot and ankle TC scans to evaluate bone growth. Results. The first four patients showed new bone formation in the calcaneus. Two patients with previous midfoot destruction showed chaotic but stable bone formation. The patient with metatarsal OM showed partial bone healing with residual pseudoarthrosis. Both the two patients who underwent arthrodesis with hybrid fixators showed a plantigrade and stable foot even though a heel wound is still present in one of the patients. All patients except this one are now wearing suitable shoes as post-operative wounds have healed. The patient still with the heel wound is walking with an aircast brace. Conclusion. The TC scans have shown new bone formation sufficient to stabilise the foot and allow ambulation. In particular, very good results come from the filling of the calcaneus, probably due to the anatomy of the bone itself

Open fractures carry a high risk of infection. Our objective was to evaluate the effect of a resorbable bone substitute (BS) (calcium sulphate and hydroxyapatite) eluting Gentamicin (Cerament™| G) in the prevention of bone infection and nonunion after open fracture and/or skin lesion. The data of patients undergoing osteosynthesis augmented with BS and Gentamicin between December 2012 and April 2015 were retrospectively analyzed from a prospectively established database. Patients were treated for open fractures grade 1 Gustilo or skin lesion with high risk of contamination. Surgical technique included initial debridement, open reduction and internal fixation (ORIF), implantation of BS and Gentamicin, soft tissue closure, and systemic antibiotic therapy for 2 weeks in all cases. Clinical outcome and radiographic bone defect filling were assessed by blinded observers. From 12/2013 to 4/2015 nine male and six female with mean age 53yrs (24–77) were treated with ORIF and BS and Gentamicin for open fractures. Fracture locations were tibial plateau (two), tibia (two), proximal humerus (one), calcaneus (four), talus (one), forearm (three), and elbow (one) distal femur (one). at final follow-up (mean 11.1 months; range 7–13). One patient developed a sterile seroma, which was treated conservatively. No post-operative infection occurred during the follow-up period. The calcium sulphate phase of BGS dissolved within 4–6 weeks in all cases. Bone ingrowth was assessed at 1, 2, 3, 6 and 12 months and new bone formation was observed at 6 months. One patient with an exposed comminuted fracture and large bone defect showed poor bone regeneration and was treated with a revision surgery (exchange of plate, autologous cancellous bone graft combined with BGS and Gentamicin. No complications were reported. The use of this bone substitute is well documented in the literature. The new product containing 175 mg gentamicin in 10 ml shows a high release of gentamicin in in-vitro testing, comparable to the elution profile of PMMA beads that some authors suggested to use to reduce the risk of infection. However, the use of this antibiotic carrier in order to prevent bone infection after open fracture has not been studied yet. In this case series 15 patients have been treated and good early clinical outcomes were observed in almost all cases. This material is highly osteoconductive and has a potential for the prophylaxis of infection in the treatment of open fractures. Further investigations and larger series are necessary to show the prophylactic effect in detail

Aim. The optimal treatment of displaced intra-articular calcaneal fractures (DIACF) remains controversial. The operative treatment group has better anatomical recovery, functional outcome scores and less pain than non operative treatment patients, but it may lead to a higher incidence of complications, such as delayed wound healing and surgical site infections. The aim of this study was to analyze the prophylactic effect using a biphasic bone substitute (BS) eluting antibiotic on calcaneal implant-related infections. Methods. We conducted a retrospective non-randomized review of all patients with DIACF (type Sanders 2, 3, 4) from 2009 to 2017; 103 calcaneal fractures of 90 patients (13 bilaterally) were treated with plates. All cases received the same systemic antibiotic prophylaxis; BS was used on more complex cases with large bone defect and BS was added with antibiotic on higher risk patients. We collected data including complications: major (deep infections, osteomyelitis) and minor complications (wound dehiscence, superficial infection). We considered the absence of deep infections after 6 months. We compared statistically the outcomes of 3 operative groups: the first was treated with plates only (A), the second with plates and BS (B) and the third with plates added with BS eluting antibiotic (vancomicine or gentamicine) (C). Results. We examined 99 cases (group A: n33, B: n52, C: n14), 4 patients were lost; the mean age was 47,8 years (range 18–83 years). Minimal follow up was 6 months (range: 6 – 42 months). We have observed 8 (8,1%) implant-related infection (A:4, 12,1%; B:4, 7,7%), 2 (2%) superficial infection (B:2, 3,8%), 20 (20,2%) wound healing defects (A:11, 33,3%; B:7, 13,5%; C:2, 14,2%). We found a relevant reduction of the rates in the group C regarding the major complications without a statistic evidence. Conclusion. The three groups are uneven; particularly the group C has a high concentration of more severe risk patients. The low number of cases in the group C, which limited the statistic evidence, represents a second limit. The absence of major infection on group C found in this study, needs larger data to confirm this result. The open surgery has an intrinsic rate of skin complications but the use of BS eluting local antibiotic is an additional tool to manage difficult complex fractures and to prevent implanted-related infection, inhibiting bacterial colonization and biofilm protection, particularly in those patients that have suffered from a minor complication, which could lead to a deep infection

It is very important to fix implant to bone. Bioactive materials as hydroxyapatite or glass-ceramics have bone-bonding ability. Hydroxyapatite-coating is applied to cementless THA or TKA. I and coworkers investigated bone-bonding mechanism of bioactive material and found that bone-like apatite formation play key role for bonding. If the surface of metal is changed to form apatite on it in body, the inert metal changes into bone-bonding material. We developed alkaline and heat treatment of titanium to change titanium to bone –bonding material as follows. At first, titanium is dipped in 5N NaOH solution for 24 hours, at second the metal is washed in pure water and finally it is sintered in 500 degree C for 2 hours. The treated surface has bioactivity, bone bonding ability like hydroxyapatite. The advantage of this treatment over hydroxyapatite-coating procedure is to treat the porous surface without any change of pore figures. As to hydroxyapatite-coating procedure, pore of the small diameter is filled with hydroxyapatite and pore figures are change. We applied this alkaline and heat treatment to cementless THA and its good results of more than ten years was reported. Porous titanium can be changed to bioactive material by alkaline and heat treatment. This bioactive porous titanium was found to have a property of material-induced osteoinduction, that is, the bone formation in pore of porous titanium implanted in canine back muscle. They can be used for bone substitute for big bone defect. We used two procedures to make porous titanium, sintering of titanium powder with spacer particle of ammonium sulfate and selective lazar melting. The latter procedure can produce any type of pore structure of titanium. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3 mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 micrometer. These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in widths 500 and 600 micrometer, with the highest observed osteoinduction occurring at 5 mm from the end of the implants. A distance of 5 mm probably provides a favorable balance between blood circulation and fluid movement. New bioactive bone cement is another topic of the application of bioactive titanium in this lecture. The bone cement contains barium sulphate for radiocontrast. We developed a procedure to replace barium sulphate with bioactive titanium powder. This new bone cement has not only better biocompatibility than conventional cement but also bone bonding ability. It is potent material for the fixation of implant to bone. I will speak the evaluation of this cement using canine model of THA

Aim. Open fractures with bone defects and skin lesions carry a high risk of infection potentially leading to prolonged hospitalization and complication requiring revision procedures. Treatment options for diaphyseal fractures with soft tissue lesions are one- or two-stage approaches using external fixation or intramedullary nailing. We describe a surgical technique combining intramedullary nailing with an antibiotic-eluting biphasic bone substitute (BBS) applied both at the fracture site, for dead-space management and infection prevention, and on the nail surface for the prophylaxis of implant-related infection. Method. Adult patients with an increased risk of bony infection (severe soft tissue damage and open fractures of Gustilo-Anderson grades I and II) were treated with debridement followed by application on the intramedullary nail surface, in the canal and at the fracture site of a BBS with prolonged elution (to 28 days) of either gentamicin or vancomycin. All patients also received systemic antibiotic prophylaxis following surgery. Data on infections and other adverse events were collected throughout the follow-up period. Bone union was determined by radiographic assessment of 4 cortices in radiographs obtained 1 year after surgery. Results. In this prospective, non-randomized case series a total of 6 patients were treated: 4 tibia (2 male, 2 female), 1 femur (female) and 1 humerus (male). The mean age of the patients was 28 years (range 18–51 years). Two patients had a history of smoking and 1 patient had a history of diabetes. Minimal Follow up was 12 months (range: 12 – 30 months). One to two weeks postoperatively, partial load bearing (20 kg) was allowed with free mobility of joints. Bone samples from the fracture site following debridement showed the presence of bacteria in 2 cases. No infections were observed during follow-up. Radiographs showed that the bone substitute was resorbed and also a gradual bony union of the fractures. All patients had good clinical outcomes. Conclusions. The addition of a BBS which elutes antibiotic locally in the dead-space of exposed fractures and at the implant surface prevents bacterial colonization and biofilm formation. The injectable composite we used enhances safety in higher risk patients, is easy to use in combination with intramedullary nailing and offers the opportunity for a one-stage procedure. Local administration of antibiotics at the fracture site provides an additional tool to manage difficult-to-treat complex fractures and implant-related infections. Larger studies are needed to confirm these results. *CERAMENT G or V, BONESUPPORT AB

Aim. In vivo studies have shown a preventive and curative effect of using an injectable vancomycin containing biphasic ceramic in an osteomyelitis model. No clinical long term pharmacokinetic release study has been reported. Inadequate concentration in target tissues results in treatment failure and selection pressure for antibiotic-resistant organisms. Our hypothesis was that vancomycin in the first week would reach high local concentrations but with low systemic levels. Method. 9 patients (6 women, 3 men) with trochanteric hip fractures classified as A1 and A2 according to the AO-classification all had internal fixations. The mean age was 75.3 years (± S.D. 12.3 years, range 44–84y). An injectable ceramic with hydroxyapatite embedded in a calcium sulphate matrix containing 66mg vancomycin per mL augmented the fixation. A mean of 9.7 mL (± S.D. 0.7 mL, range 8–10mL) was used. The elution of vancomycin was followed by collecting drain fluid, blood (4 days) and urine (4 weeks). Results. The concentration of antibiotics in the drain showed an important burst during the first 12h after surgery, with a mean value of 709.9 µmol/L (± S.D. 383.9), which decreased linearly to a mean value of 60.9 µmol/L at 2.5 days. In the urine, the vancomycin concentration reached 68.9 µmol/L (± S.D. 34.4) during the first day, which was decreased logarithmic over the first two weeks to reach zero at 20 days (see Figure). The systemic concentration of vancomycin was constantly low, not exceeding 2.6 µmol/L. Conclusions. This is the first long term pharmacokinetic study reporting vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels (wound drainage), sustained and complete release at three weeks (verified by the urine concentrations), and systemic concentrations well below toxic levels. This system should be useful in preventing and treating bone infection

This study reports the results of open reduction and internal fixation of 26 unstable, intra-articular, dorsally displaced fractures of the distal radius using a bio absorbable dorsal distal radius (Reunite) plate and calcium phosphate (Biobon) bone substitute. The bio absorbable plate has the advantages of being low profile, easily contourable due to temporary malleability and is angularly stable. It retains its strength for 6 to 8 weeks and undergoes complete mass loss within one year, thereby allowing gradual load transfer to the healing bone. In the majority of cases, this plate produces functional results comparable with metal plates. The Gartland and Werley score was excellent or good in 21 patients. The most important advantage over metal plates is in eliminating the need to remove the plate and hence the need for a second operation if implant related extensor tenosynovitis occurs. Inflammatory tissue reaction to the degradation products of the plate is a potential concern, although the co-polymer ratio used in this plate appears to have reduced the severity of this reaction, which was seen in two patients in this series. The reduction was lost in five patients with severe dorsal comminution. For such fractures, the plate did not retain its strength for long enough to allow adequate healing for satisfactory load transfer. Following this experience, we do not recommend this plating system for fractures with a metaphyseal gap of greater than 7 mm following reduction. For fractures that cannot be treated by closed means but where the metaphyseal gap following reduction is less than 7 mm, this plate provides all the theoretical advantages. Further developments allowing the plate to retain its strength for longer while maintaining the low incidence of inflammatory reactions will make it more universally applicable for the treatment of a greater spectrum of unstable distal radius fractures

Aim

Antibiotic-loaded biomaterials are often used in dead space management after excision of infected bone. This study assessed the chronological progression of new bone formation in infected defects, filled only with an absorbable, osteoconductive bone void filler with Gentamicin (1).

Aim

This study describes the histologic changes seen with a gentamicin-eluting synthetic bone graft substitute (BGS)(1) in managing bone defects after resection of chronic osteomyelitis (cOM).

Autologous bone grafting for bone defect reconstruction is associated with complications including donor site morbidity, infection risk, pain and surgical time. Therefore, bone graft substitutes provide an alternative for distinct indications and different characteristics with regard to their mechanical properties and resorption rates. In order to fill the loss of bone substance and to control the infection, we tried the efficacy of Cerament™G, a new absorbable composite of Calcium Sulphate and Hydroxyapatite with Gentamicin.

We present 3 male patients aged between 45 and 68 years affected by post-traumatic severe septic non union of femur, tibia and foot. The first patient with femur fracture was involved in a car accident (mixed flora Acinetobacter Baumanii, MRSA and Klebsiella pneumoniae carbapenemase (KPC)-producing), the second patient with femur and foot fracture falled by height in a work accident (MRSA) and the third one had a chronic tibial osteomyelitis several years after a road accident (Pseudomonas Aeruginosa). All 3 patients had undergone previous surgery. The first patient had several operations including multiple bone resection and debridement with external fixator, occlusion of superficial femoral artery with arterial bypass and finally debridement with implantation of Cerament™ G with external fixator and long term antibiotic therapy. The other 2 patients were subjected to resection of tissue septic with debridement, implantation of Cerament™ G and soft tissue closure and systemic antibiotics. Clinical and radiographic outcome were assessed at final follow-up (mean 8 months; range 8–18)

The follow-up was 8–18 months with examining clinical, radiographic, CT scan and laboratory tests. The patients had self-limiting fluid leakage. There was no recurrence of infection during the follow-up period. Bone ingrowth occurred in all cases with limb shortening.

Cerament™ G gives good elution of antibiotic and allows bone ingrowth. The implantation of Cerament™ G was associated with good clinical outcomes and satisfactory bone consolidation.

We acknowledge Antonella Esposito for septic nursing assistance

Introduction. Treatment of non-union in open tibial fractures Gustilo-Anderson(GA)-3A/3B fractures remains a challenging problem. Most of these can be dealt using treatment methods that requires excision of the non-union followed by bone grafting, masquelet technique, or acute shortening. Circular fixators with closed distraction or bone transport also remains a useful option. However, sometimes due to patient specific factors these cannot be used. Recently antibiotic loaded bone substitutes have been increasingly used for repairing infected non-unions. They provide local antibiotic delivery, fill dead space, and act as a bone conductive implant, which is resorted at the end of a few months. We aimed to assess the outcome of percutaneous injection of bone substitute while treating non-union of complex open tibial fractures. Materials & Methods. Three cases of clinical and radiological stiff tibial non-union requiring further intervention were identified from our major trauma open fracture database. Two GA-3B cases, treated with a circular frame developed fracture-related-infection(FRI) manifesting as local cellulitis, loosened infected wires/pins with raised blood-markers, and one case of GA-3A treated with an intramedullary nail. At the time of removal of metalwork/frame, informed consent was obtained and Cerament-G. TM. (bone-substitute with gentamicin) was percutaneously injected through a small cortical window using a bone biopsy(Jamshedi needle). All patients were allowed to weight bear as tolerated in a well-fitting air-cast boot and using crutches. They were followed up at 6 weekly intervals with clinical assessment of their symptoms and radiographs. Fracture union was assessed using serial radiographs with healing defined as filling of fracture gap, bridging callus and clinical assessment including return to full painless weight bearing. Results. Follow-up at 6 months showed all fractures had healed with no defect or gaps with evidence of new trabecular bone and significant resorption of Cerament-G. TM. at final follow-up. There was no evidence of residual infection with restoration of normal limb function. Fractures with no internal fixation showed a mild deformity that had developed during the course of the healing, presumed due to mild collapse in the absence of fixation. These were less than 10 degrees in sagittal and coronal planes and were clinically felt to be insignificant by the patients. Conclusions. Cerament-G's unique combination of high dose antibiotics and hydroxy apatite matrix provided by calcium sulphate might help provide an osteoconductive environment to allow these stiff non-unions to heal. The matrix appears to provide a scaffold-like structure that allows new bone in-growth with local release of antibiotics helping reduce deep-seated infections. The final deformation at fracture site underlines the need for fixation- and it is very unlikely that this technique will work in mobile nonunions. Whilst similar fractures may heal without the use of bone substitute injections, the speed of healing in presence of significant fracture gap suggests the use of these bone substitutes did help in our cases. Further studies with a larger cohort, including RCTs, to evaluate the effectiveness of this technique compared to other methods are needed

Introduction. Various biomaterials and bone graft substitute technologies for use in osteomyelitis treatment are currently used in clinal practice. They vary in mode of action (with or without antibiotics) and clinical application (one-stage or two-stage surgery). This systematic review aims to compare the clinical evidence of different synthetic antimicrobial bone graft substitutes and antibiotic-loaded carriers in eradicating infection and clinical outcome in patients with chronic osteomyelitis. Methods. Systematic review according to PRISMA statement on publications 2002-2023. MESH terms: osteomyelitis and bone substitutes. FREE terms: chronic osteomyelitis, bone infection. A standardized data extraction form was be used to extract data from the included papers. Results. Publications with increased methodological quality and clinical evidence for biomaterials in osteomyelitis treatment were published in the last decades. High 85-95% eradication rates of osteomyelitis were observed for various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass. Level of evidence varies significantly between products. Antibiotic pharmacokinetic release profiles vary between resorbable Ca-P and/or Ca-S biomaterials. Conclusion. Given the high 85-95% eradication rates of osteomyelitis by various resorbable Ca-P and/or Ca-S biomaterials combined with antibiotics and S53P4 bioactive glass, one-stage treatment is preferred. Surgeons should be aware of variations in mechanical properties and antibiotic pharmacokinetic release profiles between Ca-P and CA-s products. Mechanical, biological and antimicrobial properties of bioactive glass are formulation dependent. Currently, only S53P4 bioactive glass has proven antimicrobial properties. Based on this systematic review antibiotic loaded fleeces should be used with caution and restraint

Aim. Since July 2013 our group has been using an antibiotic bone substitute, composed of calcium sulphate, hydroxyapatite and gentamicin sulphate (CSH + HA + GS), in the treatment of osteomyelitis (OM) in diabetic foot. The aim of this work was to evaluate the mid-term efficacy of this treatment regime on outcomes. A favourable outcome in diabetic foot includes no recurrence of OM, healed soft tissues and the ability to weight-bear. Method. To date we have used the CSH + HA + GS bone substitute in 24 diabetic patients with OM. In this study we reviewed patients treated from July 2013 to December 2014, in which we used CSH + HA + GS to treat OM of the forefoot, midfoot and hind foot, and evaluated how many patients are able to walk and fully weight-bear at present. We identified 11 pts treated during this time period; 1 with bilateral 1. St. metatarsal-head OM due to plantar ulcers, 5 with midfoot OM secondary to Charcot deformities and ulcers, 5 with hind foot OM due to pressure ulcers or Charcot deformity. We continuously monitored the patients for recurrence of OM, ulcers and soft tissue inflammation in our outpatient department. Results. Of the 11 patients, two died during follow up (both patients had calcaneal ulcers; one died in the 1. st. month and one in the 2. nd. month after treatment, both due to cardiovascular disease). For the remaining nine patients, we had an average of 25 (17–33) months follow-up. One patient did not heal, presenting with a persistent mid-foot lesion in a Charcot foot. Another patient with bilateral forefoot ulcers had a plantar ulcer recurrence under the left 1. st. metatarsal foot, 19 months after bone substitute application and primary healing. This patient is still weight-bearing on the right foot, as are the remaining 6 patients. In 7 patients (1 with bilateral forefoot, 4 with mid-foot and 3 with hind foot OM) no recurrence of OM or ulcers was observed. Conclusions. This study suggests that a CSH + HA + GS bone substitute can be used to treat diabetic foot OM. Our mid-term results show good clinical outcomes in terms of ulcer healing, no recurrence of OM and weight-bearing

Introduction. Little guidance exists regarding the minimum screw length and number necessary to achieve fixation with reverse shoulder arthroplasty (rTSA). The goal of this study is to quantify the pre- and post-cyclic baseplate displacements associated with two baseplate designs of different sizes using multiple screw lengths and numbers in a low density polyurethane bone substitute model. Methods. The test was conducted according to ASTM F 2028–17. The baseplate displacements of standard and small reverse shoulder constructs (Equinoxe, Exactech, Inc.) were quantified in a 15pcf polyurethane block (Pacific Research, Inc.) before and after cyclic testing with an applied load of 750N for 10,000 cycles. Baseplates were constructed using 2 or 4 screws with 3 different poly-axial locking compression screw lengths: 4.5×18mm, 4.5×30mm, and 4.5×46mm. Five of each configuration were tested for a total of 30 specimens for each baseplate. A two-tailed, unpaired student's t-test (p<0.05) compared baseplate displacements before and after cyclic loading in both the superior-inferior (S/I) and anterior-posterior (A/P) directions. The standard and small results were then compared. Results. All standard and small reverse glenoid baseplates remained well-fixed after cyclic loading in the low-density bone substitute model regardless of screw length or number. The average pre- and post-cyclic displacement for baseplates with 2 screws was significantly greater than that of baseplates with 4 screws in both the A/P and S/I directions. The average pre- and post-cyclic displacements for baseplates with 18mm screws were significantly greater than baseplates with 46mm screws in the A/P and S/I directions, post-cyclic displacement with 18mm screws was significantly greater than with 30mm screws in the A/P and S/I directions, and post-cyclic displacement with 30mm screws was significantly greater than with 46mm screws in the S/I direction only. Few differences in fixation were observed between baseplate sizes. Statistically significant difference was reached for post cyclic S/I displacement for 30mm (small baseplate superior) and 46mm screws (standard baseplate superior). Discussion and Conclusions. The results demonstrate that rTSA glenoid displacement is impacted by both the number and length of screws for both standard and small baseplate sizes. Regardless of the number of screws, the use of longer screws was associated with significantly better initial fixation. Additionally, the use of more screws was associated with significantly better fixation irrespective of screw length in the A/P direction. None of the tested devices catastrophically failed, demonstrating that adequate fixation can be achieved with as little as two 18mm screws for the baseplates utilized. However, this screw configuration was associated with the largest pre- and post-cyclic displacements, so it is assumed to be at a greater risk for aseptic loosening. If using 4 screws is not feasible in a given case, the results suggest that using longer screws can be used to improve fixation. The results of the small and standard baseplates were comparable for the given lengths and quantities of screws, suggesting that the reduced surface area of the small baseplate has no detrimental impact on fixation. Care should be made when extrapolating these results to glenoid defects. For any figures or tables, please contact authors directly

Evaluation of the effectiveness of biodegradable bone substitute with high doses of antibiotics in cavitary osteomyelitis and infected nonunions. The authors evaluated 8 cases, 5 of them related to osteomyelitis with bone sequestration and other 3 regarding infected nonunions. All of them had in common the persistence of infection after antibiotic therapy. All infections were confirmed by microbiological studies. In all cases the surgeons conducted a thorough surgical debridement and filling of bone defects with Herafill®. Later a tight clinical, analytical and imagiological control was performed. Five of the cases were a success with simultaneous healing of the bone loss and treatment of the infection. These corresponded to the cases of cavitary osteomyelitis. In the remaining 3 cases, despite infection eradication, union was not achieved and additional surgical procedures were required for definitive treatment of nonunion. In the treatment of bone infection, use of high doses of antibiotics at the site is a consensus as it allows eradication of the infection with lower systemic effects. With the emergence of biodegradable bone substitutes, the need for a new surgical intervention for their removal can be avoided. Properties of calcium sulfate and calcium carbonate stimulate osteogenesis at the site, allowing their absorption and replacement by bone matrix. These properties make them ideal to usage in cases of cavitary bone defects. Our experience supports the idea that the use of high doses of antibiotics locally permits remission of the infection. However, when this is implemented through a bone substitute, it is possible to achieve osteogenesis in bony cavities. Nevertheless, when applied to infected nonunions, their role seems to be limited to the eradication of the infection