A spine compression fracture is a very common form of fracture in elderly with osteoporosis. Injection of polymethyl methacrylate (PMMA) to fracture sites is a minimally invasive surgical treatment, but PMMA has considerable clinical risks. We develop a novel type thermoplastic injectable bone substitute contains the proprietary composites of synthetic ceramic bone substitute and absorbable thermoplastic polymer. We used thermoplastic biocompatible polymers Polycaproactone (PCL) to encapsulate calcium-based bone substitutes hydroxyapatite (Ca10(PO4)6(OH)2, HA) and tricalcium phosphate (TCP) to form a biodegradable injectable bone composite material. The space occupation ration PCL:HA/TCP is 1:9. After heating process, it can be injected to fracture site by specific instrument and then self-setting to immediate reinforce the vertebral body. The thermoplastic injection bone substitute can obtain good injection properties after being heated by a heater at 90˚C for three minutes, and has good anti-washout property when injected into normal saline at 37˚C. After three minutes, solidification is achieved. Mechanical properties were assessed using the material compression test system and the mechanical support close to the vertebral spongy bone. In vitro cytotoxicity MTT assay (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed and no cell cytotoxicity was observed. In vivo study with three New Zealand rabbits was performed, well bone growth into bone substitute was observed and can maintain good mechanical support after three months implantation. The novel type thermoplastic injection bone substitute can achieve (a) adequate injectability and viscosity without the risk of cement leakage; (b) adequate mechanical strength for immediate reinforcement and prevent adjacent fracture; (c) adequate porosity for new bone ingrowth; (e) biodegradability. It could be developed as a new option for treating vertebral compression fractures

Objectives. The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month. Methods. Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine. Results. The antibiotic concentration in the drain reached a peak during the first six hours post-surgery (mean 966.1 mg/l), which decreased linearly to a mean value of 88.3 mg/l at 2.5 days. In the urine, the vancomycin concentration reached 99.8 mg/l during the first two days, followed by a logarithmic decrease over the next two weeks to reach 0 mg/l at 20 days. The systemic concentration of vancomycin measured in blood serum was low and decreased linearly from 2.17 mg/l at one hour post-surgery to 0 mg/l at four days postoperatively. Conclusion. This is the first long-term pharmacokinetic study that reports vancomycin release from a biphasic injectable ceramic bone substitute. The study shows initial high targeted local vancomycin levels, sustained and complete release at three weeks, and systemic concentrations well below toxic levels. The plain ceramic bone substitute has been proven to regenerate bone but should also be useful in preventing bone infection. Cite this article: M. Stravinskas, M. Nilsson, A. Vitkauskiene, S. Tarasevicius, L. Lidgren. Vancomycin elution from a biphasic ceramic bone substitute. Bone Joint Res 2019;8:49–54. DOI: 10.1302/2046-3758.82.BJR-2018-0174.R2

Summary. A promising approach to stimulate in vivo bone formation by using our newly developed magnesium-based bone substitutes, which can be an alternative to treat the patients with bone loss in addition to the anticatabolic drugs and growth factors. Introduction. Bone impairment arising from osteoporosis as well as other pathological diseases is a major health problem. Anti-catabolic drugs such as bisphosphonates and other biological agents such as bone morphogenetic proteins and insulin-like growth factor can theoretically apply to stimulate bone formation. However, the formation of more brittle bone and uncontrolled release rate are still a challenge nowadays. Hence, we propose to stimulate bone formation by using a newly developed magnesium-based bone substitute. Indeed, the presence of magnesium ions can stimulate bone growth and healing by enhancing osteoblastic activity. This study aims to investigate the mechanical, in vitro and in vivo properties of this novel bone substitute. Methods. The bone substitutes were prepared by incorporating 9% TMSPM-treated Mg granules (i.e. 45μm & 150μm) into biodegradable polymer, polycaprolactone (PCL). The TMSPM silane-coupling agent treatment was used to protect the Mg particles from rapid degradation. Compression test was performed to study the mechanical properties of the bone substitute by using the MTS machine. A 7-day stimulated body fluid (SBF) immersion test was conducted to test their bioactivity. The surface composition was checked by energy dispersive x-ray spectroscopy (EDX) after immersion. The cytocompatibility and osteogenic differentiation properties of the bone substitutes were studied by MTT, ALP assays and qRT-PCR with the use of MC3T3-E1 pre-osteoblasts. Finally, the in vivo response of the bone substitutes was evaluated by using rat model of 2 months. Micro-CT was used to monitor the volume change of bone formation. Pure PCL was used as the control. Results. At least 36% higher compressive modulus was found on the new bone substitutes as compared to pure PCL. Calcium and phosphate deposition were detected on the Mg bone substitutes but not on pure PCL after 7-day SBF immersion. Significantly higher cell viabilities and specific ALP activities were found on the new bone substitutes as compared to pure PCL. Additionally, significantly higher ALP, Type I collagen, osteopontin and Runx2 expressions were found on the Mg-based substitutes at different time points. Finally, more than 15% new bone was found on the Mg bone substitutes after 1 week of post-operation and 40% higher after 3 weeks. Discussion/Conclusion. The increased compressive moduli of the Mg-based bone substitutes suggested that the mechanical property of PCL could be enhanced by incorporating Mg granules and the values fall within the range of cancellous bone (50 – 800 MPa). Moreover, the detection of the calcium and phosphate on the bone substitutes showed that they might possess osteoinductivity. The in vitro study showed the enhanced cytocompatibility and osteogenic differentiation properties of the new bone substitutes, which was possibly due to the effect of Mg ions release. Our previous study showed that only a low level of Mg ions (i.e. 50ppm) is able to stimulate the growth and differentiation of osteoblasts. Hence, this suggested the importance of controlling the release of Mg ions. This also explained why more new bone formation was found on the new bone substitutes than pure PCL during animal implantation. Hence, all the data presented here suggested our new bone substitutes maybe a potential candidate to stimulate new bone formation

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

Bone loss continues to be a clinical and therapeutic problem. Bone reconstruction of osseous defects is a challenge after fracture and traumatic injuries, infections and tumors. The common objective is to regenerate bone morphology and function. Several techniques have been developed to promote bone formation, but the advent of new biomaterials allows us to take an entirely different approach to the treatment of bone voids. However, the use of bone substitutes should be considered carefully, as not all biomaterials behave the same way in humans. Calcium phosphate ceramics are osteoconductive materials that promote bone regeneration. The aim of this study was to retrospectively evaluate the clinical, radiographic and histological results of bone loss treated with an adjunct injectable biphasic bone substitute (BBS). We analysed the results of patients with fractures and a bone defect that were treated using an injectable BBS (calcium sulfate + hydroxyapatite) and those that were treated using the same bone substitute with antibiotic (gentamicin and/or vancomycin). Patient outcome was evaluated clinically and radiographically. In 9 cases samples for histological analysis were obtained. From July 2009 to May 2015, 126 cases (cs) on 111 patients (pt) (calcaneus: 53 cs, 47 pt; tibia: 32 cs, 30 pt; Femur: 14 cs, 9 pt, Elbow: 5 cs, 5 pz; humerus 2 cs, 2 pz; wrist 7cs, 7pz; forearm 6 cs, 4 pz; foot 2 cs, 2 pz; Phalanx 5 cs, 5 pt) were treated at our hospital with a BBS. The mean follow-up was 15 months, and bone ingrowth was assessed at 1, 2, 3, 6 and 12 months by X-ray. In all cases, the calcium sulphate phase of the BBS dissolved within 4–6 weeks, and new bone formation was observed at 6 months. On six patients large bone was treated with a revision surgery (autologous cancellous bone graft combined with BBS and antibiotic). No complications were reported. The 9 histological samples confirmed gradual remodeling and regeneration of the bone substitute over time. This biomaterial is versatile, offers a good augment for hardware and bone alignment, is biocompatible and osteoconductive, and has allowed us to manage significant bone voids. Histological analysis of samples from the tibia, ulna and calcaneus have confirmed the ability of this bone substitute to remodel into bone

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

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

Aims: Hydroxyapatite (HA) is widely known in orthopaedic surgery and is proved to be safe and effective in bone substitution. Actually synthetic HA is a merely reproduction of the chemical constitutes of the natural HA (Ca, P). New technologies demonstrate that it is possible to assembly new materials starting from the primary microscopic unit (nano molecules) with a process called “bottom to the top”, realizing macromolecules biologically active and smart. Even bone is nano structured in HA crystalline units (20–40 nm) regularly oriented upon collagen fibres (300 nm). Methods: This study concern a new nano structured HA realized by an auto assembled process “biologically inspired”, like in human bone formation, of nano HA crystals and collagen as to realize a new material very similar to natural bone. Samples of the nano-HA were tested in living bone in vivo (rabbits) and compared with a synthetic Mg-HA (Ha added with Magnesium). Macroscopic, radiographic, light microscopic and SEM analysis were performed periodically. New osteogenesis, bone ingrowth and ongrowth, bone apposition rate were evaluated up to 12 weeks. :The preliminary results of this study showed for both the biomaterials optimal bone apposition and biocompatibility. In the first month an earlier osseointegration was observed in traditional Mg-HA samples. The histological examination revealed a primary direct bone apposition from the surrounding living bone. The Nano-HA samples showed a slower secondary bone apposition, may be because of the initial larger gap and consequent lesser direct contact between the material and the guest bone. No adverse effect or reactive phenomenon were observed. Conclusions: This study demonstrates the reliability of this new nano structured HA that demonstrates to be biologically active and useful in bone substitution. Further studies will reveal new promising improvements in bone substitution with interesting multidisciplinary innovations

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

In order to improve hydroxyapatite (Ha) quality as a bone substitute, two types of Ha were developed based on a new and original technique: Ha with graduated porosity (G-Ha) and porous “carbonated” Ha (C-Ha). Ha cylinders were implanted into the femoral diaphysis of NZW rabbits. Before implantation the materials were characterised by XRD, porosimetry, SEM and thermic and mechanical analysis. Macroscopic, radiographic and histologic analysis were performed on the specimens at standard intervals after surgery (1-3-6- and 12 months). G-Ha proved to be morphologically more similar to bone tissue because of the graduated porosity that mimes the two natural components of bone (cortical-scarce porosity and spongious-high porosity). The C-Ha was chemically more similar to bone because of the CO. 3. - substitution, which is a normal substitute in natural bone. Both materials achieved good mechanical strength, in particular the pseudo-cortical portion of G-Ha. Interconnected porosity was also observed in both materials. Newly formed bone appeared earlier in C-Ha (1–3 months). At 1 year C-Ha demonstrated quiescent bone and significant degradation. The G-Ha was scarcely reabsorbed but showed active osteogenesis in the surrounding living bone. Graduated porosity improved the mechanical interaction with bone over time, while the carbonation improved the temporal interaction and Ha resorption. Porous Ha was found to be a promising bone substitute and also a reliable drug-delivery carrier

Introduction: Seven patients underwent successful revision total knee replacement for aseptic loosening. Bovine bone graft was used to reconstruct bony defects in all. Materials and methods: This is a retrospective review. Between April 2000 and March 2003, bovine bone (Tutobone™, Wescott-Medical, UK) was used in 7 revision arthroplasty cases (4 right knees & 3 left). There were 5 males and 2 females. The average age was 70.4 years. All revisions were carried out for aseptic loosening of the prostheses associated with massive osteolysis and bone loss. The bone defects on the tibia and femur were as follows: (Obtained from operative records. Classified according to Anderson Orthopaedic Research Institute classification). Type I. Type IIA. Type IIB. Type III. TIBIA. 3. 1. 2. 1. FEMUR. 2. 3. 2. 0. The tibial defects were corrected by impaction grafting and femoral condyle defects were corrected by using bovine bone as bulk grafts. Semi-constrained constrained stemmed cemented modular knee prostheses (TC3, Depuy) were used in all. Clinical outcomes were recorded by the Oxford Knee Score. Serial radiographs were evaluated for graft density, integration, implant loosening, alignment and subsidence. Results: At recent follow-up, radiographs showed good graft integration, no loosening, and no subsidence of the implant and good prostheses alignment. The average Oxford Knee Score was 20.4. Conclusion & discussion: Bovine bone substitute is an alternative. The bone defects in these patients were successfully reconstructed with bovine bone. It is an osteo-conductive matrix with intact type-I collagen that provides mechanical stability. It is also cost effective. Early results are encouraging but long-tem follow-up is needed

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

Bone substitutes have emerged as a promising alternative in surgeries requiring bone grafting, with a large array of materials available for today’s surgeon. Unfortunately, there is currently no definitive method for comparing the potential bone-healing potential of these different materials. We have developed a novel technique for assessing the osteogenic capacity of different bone substitutes in a mechanically-stimulating perfusion bioreactor. The Zetos(TM) bioreactor system consists of individual flow chambers connected to a low-flow perfusion pump, which recirculates media through samples. The Zetos can be programmed to apply a controlled stress or a controlled strain to each individual sample inside the flow chamber. Since bone formation has been shown to be optimal with short doses of high amplitude strains, test samples were subjected to daily loading corresponding to physiological strain experienced during a jumping exercise (maximum 3000 microStrain). Three substitute materials representing the range of materials available clinically were tested in the Zetos system; these included collagen, calcium phosphate, and a synthetic polymer. Primary human osteoblasts were seeded onto the substitutes, which were then placed inside the Zetos system and maintained under load or non-load conditions for 14 days. No supplementary osteogenic factors were provided to the cells. The degree of bone formation in the samples was assessed using Von Kossa staining and quantified in terms of the area of new mineral relative to the surface area of the substitute. No mineralisation was detected in the non-loaded samples. However, in the loaded samples, mineralisa-tion was detected in some of the substitutes. The degree of mineralisation depended on the material: in collagen, an average of 0.22 mm2/mm2 was mineralised; in calcium phosphate, mineralisation averaged 0.0013 mm2/ mm2; but in the loaded polymer samples, no mineralisation was detected. This indicates that mechanical loading is a sufficient stimulus for bone formation in some materials, even in the absence of other known osteogenic factors. Further, commercial substitutes differ in their ability to support bone formation under conditions of physiological loading. Further development of this technique could allow it to be used as a screening tool for predicting the efficacy of commercial products

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

Aims: Wood is a product of nature, has a structural architecture resembling bone and is chemically polymer-like. Birchwood modified with heat and humid air was selected to study its possibilities for bone reconstruction. Methods: Bulk birchwood was prepared for 2–3 hours at temperature of 220°C in humid air, this modifies the wood chemically and physically. 16 cone shaped implants 7x4 mm in size were carved from the heat treated material (Bioactive Wood Bone, BWB) and implanted by press-fit technique into holes drilled in the distal femurs of rabbits. Untreated cones served as controls. The resected knees were embedded in plastic (Techmont, Kulzer GmBH). For evaluation histology, histomorfometry and scanning electron microscopy (SEM) were carried out. Results: In vitro SEM showed the canal structures of the wood. In vivo no articular hydrops or wound infections were seen. At 4 and 8 weeks an inflammatory cellular reaction of a mild degree with some histiocytes was observed. At 8 and 20 weeks the implant’s surface was in connection with the surrounding bone and connective tissue. Bone-implant contact at the interface required proper press-fit technique. At 8 and 20 weeks histometry revealed new bone growth covering 21% (mean, range 6–41%) of the implant surface resembling the osteoconductive bonding characteristic of biomaterials. Conclusions: Modified heat treated wood showed biocompatibility and osteoconductivity in cancellous bone defect. A bone bonding-like-phenomenon observed at the interface between the birch implant and bone illustrates it’s potentials for use as a bone substitute

Introduction: The incidence of contralateral, second hip fractures after a first hip fracture is as high as 20% in the elderly. Femoroplasty using an injectable and resorbable bi-phosphonate loaded bone substitute to prevent controlateral hip fracture may represent a promising preventive therapy. We aimed to evaluate the biomechanical consequences of the femoroplasty using this bone substitute. Materials and Methods: Twelve paired human cadaveric femora from donors with a mean age of 86 years (7 women and 6 men) were randomly assigned for femoroplasty and biomechanically tested for fracture load against their native contralateral control. Anterior–posterior and lateral radiographs and DXAscan’s were made before injection. Femoroplasty were performed under fluoroscopic guidance with an injectable and resorbable bi-phosphonate loaded bone substitute. All femurs were fractured by simulating a fall on the greater trochanter by an independent observer. Results: Mean T-score of the tested femur were −3. Bone density was comparable for each pair of femur. All the observed fractures were Kyle II throchanteric fractures. Mean fracture load was 2786 Newton in the femoroplasty group (group F) versus 2116 Newton in the control group (group C) (p< 0.001). Fracture loads were always higher in the group F: mean 41.6% (mini: 1.2%/maxi:102.1%). Effect of femoroplasty was significantly superior for women and also correlated to initial bone density (p< 0.0001). Discussion:According to our results, femoroplasty with an injectable and resorbable bi-phosphonate loaded bone substitute can provide significant biomechanical reinforcement of the proximal femur to prevent controlateral fracture