We reviewed 59 bone graft substitutes marketed by 17 companies currently available for implantation in the United Kingdom, with the aim of assessing the peer-reviewed literature to facilitate informed decision-making regarding their use in clinical practice. After critical analysis of the literature, only 22 products (37%) had any clinical data. Norian SRS (Synthes), Vitoss (Orthovita), Cortoss (Orthovita) and Alpha-BSM (Etex) had Level I evidence. We question the need for so many different products, especially with limited published clinical evidence for their efficacy, and conclude that there is a considerable need for further prospective randomised trials to facilitate informed decision-making with regard to the use of current and future bone graft substitutes in clinical practice. Cite this article: Bone Joint J 2013;95-B:583–97

Aims. Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects. Methods. We performed a retrospective review at a single institution of patients undergoing revision THA by a single surgeon. We identified 49 consecutive patients with large acetabular defects where the biphasic BGS was applied, with no other products added to the BGS. After placement of metallic acetabular implants, the BGS was injected into the remaining bone defects surrounding the new implants. Patients were followed and monitored for functional outcome scores, implant fixation, radiological graft site remodelling, and revision failures. Results. Mean follow-up was 39.5 months (36 to 71), with a significant improvement in post-revision function compared to preoperative function. Graft site remodelling was rated radiologically as moderate in 31 hips (63%) and strong in 12 hips (24%). There were no cases of complete graft site dissolution. No acetabular loosening was identified. None of the patients developed clinically significant heterotopic ossification. There were twelve reoperations: six patients developed post-revision infections, three experienced dislocations, two sustained periprosthetic femur fractures, and one subject had femoral component aseptic loosening. Conclusion. Our series reports bone defect restoration with the sole use of a biphasic injectable BGS in the periacetabular region. We did not observe significant graft dissolution. We emphasize that successful graft site remodelling requires meticulous recipient site preparation. Cite this article: Bone Jt Open 2022;3(12):991–997

Objectives. Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results. The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions. This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute: In vitro and clinical release studies. Bone Joint Res 2016;5:427–435. DOI: 10.1302/2046-3758.59.BJR-2016-0108.R1

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

To document early in-vivo concentrations of gentamicin in plasma and drain fluid after bone defect reconstruction using a gentamicin-eluting bone graft substitute. Introduction. Reconstruction of bone defects after surgical bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis(1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent bone defect reconstruction with a gentamicin-eluting bone graft substitute (CERAMENT™|G – BONESUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting bone graft substitute was used, either alone or in combination with cancellous allograft and/or a bone graft substitute not containing gentamicin (CERAMENT™|BVF – BONESUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2. Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting bone graft substitute for bone defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations

Aim. Bone and implant-associated infections caused by microorganisms that grow in biofilm are difficult to treat because of persistence and recurrence. Systemic administration of antibiotics is often inefficient because the poor vascularization of the site of infection. This issue has led to the development of biomaterials capable to locally deliver high doses of therapeutic agents to the injured bone with minimal systemic effects. In this context, calcium sulphate/hydroxyapatite (CS/HA) bone graft substitutes are widely used being safe, osteoconductive and resorbable biomaterials that can be easily enriched with consistent amounts of antibiotics. In this in vitro study, the capability of the eluted antibiotics to select the tested bacterial strains for antibiotic resistance was evaluated to confirm the safe use of the product. Method. S. aureus, S. epidermidis and P. aeruginosa isolated in our Institute from bone and joint infection with different resistance phenotypes were used. 6 × 2.5 mm CS/HA discs were generated by pouring the antibiotic loaded formulations in a mold and were used as a modified disk diffusion test. The resistance selection was evaluated by subculturing cells growing on the edge of the zone of inhibition (ZOI) for seven days. Minimum inhibitory concentrations (MICs) of gentamicin and vancomycin were determined by broth microdilution method before and after the selection of resistance assay. In addition, MICs were assessed after seven day passage on antibiotic free agar plates to evaluate if eventual decrease of antibiotic susceptibility was stable or only transient. Results. Commonly, no adaptation in presence of both CS/HA formulations was observed by analysing ZOI on agar medium. The kinetic of decrease of the ZOI was similar between the strains, with the exception of gentamicin resistant staphylococci in presence of gentamicin loaded CS/HA, which was faster with respect to the susceptible strains. Conclusions. The present study shows that elution of gentamicin and vancomycin from CS/HA bone graft substitutes did not induce a decrease in susceptibility to these antibiotics in an in vitro setting, suggesting the safe use of the product

Aim. This study describes and correlates the radiographic and histologic changes which develop in a Gentamicin-eluting synthetic bone graft substitute. *. in the management of bone defects after resection of chronic osteomyelitis (COM). Method. 100 patients with COM were treated with a single stage procedure, including management of the dead space with insertion of a Gentamicin-eluting synthetic bone graft substitute. *. Radiographs of 73 patients with a follow-up of at least 12 months (range 12–33 months) were available for review. Bone defects were diaphyseal in 32, metaphyseal in 34 and combined in 7 patients. In 3 patients, radiographs were not of sufficient quality to allow analysis. Five patients had subsequent surgery, not related to recurrence of infection, which allowed biopsy of the implanted material. These biopsies were harvested between 12 days and 9 months after implantation. Tissue was fixed in formalin and stained with haematoxylin-eosin and immunohistochemically for bone matrix markers. Results. Radiographic: 31 of 34 diaphyseal implantations (91%) demonstrated remodelling of the biocomposite, gradually over many months, producing new bone and resulting in a “normal post-osteomyelitic” appearance. In metaphyseal implantations, new bone filled two-thirds or more of the defect in 55% of cases, one to two-thirds was filled in 31% and one third or less was filled in 14%. 22% of patients exhibited radiographic signs of dissolution and remodelling which are specific to this material. The ‘Halo’ sign of peripheral zone remodelling, the ‘Marble’ sign of dissolution and the ‘Puddle’ sign of distal migration can be described. Histologic: Histological assessment revealed early active remodelling of the biocomposite. The material was osteoconductive with accumulation of osteoblasts and osteoid and woven bone formation on the surface of the Gentamicin-eluting synthetic bone graft substitute. *. separated by fibrous tissue at the edge of the defect beneath reactive viable host bone. Fibrous tissue contained a heavy macrophage infiltrate and the newly formed matrix contained the specific bone proteins, dentine matrix protein-1 and podoplanin. There was limited evidence of remodelling into lamellar bone at 20 weeks after implantation. Conclusions. The Gentamicin-eluting synthetic bone graft substitute. *. exhibits a specific pattern of radiographic change over many months after implantation. The resolution of the bone defect would appear to be due to bone formation, as seen in the histologic and immunohistochemical analysis

Bioactive glasses (BAGs) are bone substitutes with bone bonding, angiogenesis promoting and antibacterial properties. The bioactive process leading to bone bonding has been described as a sequence of reactions in the glass and at its surface. Implantation of the glass is followed by a rapid exchange of Na+ in the glass with H+ and H3O+ from the surrounding tissue, leading to the formation of silanol (SiOH) groups at the glass surface. Due to migration of Ca2+ and PO43− groups to the surface and cystallization, a CaO-P2O5 hydroxyapatite (HA) layer is formed on top of the Si-rich layer. Finally, cell interactions with the HA layer subsequently initiate the bone forming pathway. The rapid increase in pH and the subsequent osmotic effect caused by dissolution of the glass have been suggested to partly explain the antibacterial properties observed for BAGs. Comparing bactericidal effects of different BAGs, BAG-S53P4 has been shown to be the most effective, with the fastest killing or growth inhibitory effect. This antibacterial effect has been observed in vitro for all pathogens tested, including the most important aerobic and anaerobic pathogens, as well as very resistant bacteria. In a multicentre study in 2007–2009, BAG-S53P4 was used as bone graft substitute in treatment of osteomyelitis. Eleven patients (nine males, two females) with a radiologically diagnosed osteomyelitis in the lower extremity (N=10) and in the spine (N-1) participated. In the operation, the infected bone and the soft tissue were removed, and the cavitary bone defects were filled with BAG-S53P4 (BonAlive™, Bonalive Biomaterials Ltd., Finland). In four patients, muscle flaps were used as part of the treatment. Eight patients were treated in a one-stage procedure. Kanamycin granules were used in one patient and Garamycin granules (Septocol ®) in two patients. Patient data were obtained from hospital patient' records until August 2010, resulting in a mean follow-up period of 29 months (range 15–43). BAG-S53P4 was well tolerated; no BAG-related adverse effects were seen in any patient. The use of BAG-S53P4 as a bone graft substitute resulted in a fast recovery. Long-term clinical outcome was good or excellent in ten of eleven patients. These primary results indicate that BAG-S53P4 can be considered as a good and usable material in treatment of osteomyelitis. After this study BAG-S53P4 has been used in several other patients with very promising results

To report our experience with the use of local antibiotic co-delivery with a synthetic bone graft substitute during a second stage re-implantation of an infected proximal humeral replacement. A 72 year old man was admitted to our department with a pathological fracture through an osteolytic lesion in the left proximal humerus, due to IgG Myelomatosis. He was initially treated with a cemented proximal humerus replacement hemiarthroplasty. Peri-prosthetic joint infection (PJI) with significant joint distention was evident three weeks post operatively. Revision surgery confirmed presence of a large collection of pus and revealed disruption of the soft tissue reattachment tube, as well as complete retraction of rotator cuff and residual capsule. All modular components were removed and an antibiotic-laden cement spacer (1.8g of Clindamycin and Gentamycin, respectively) was implanted onto the well-fixed cemented humeral stem. Initial treatment with i.v. Amoxicillin/Clavulanic acid was changed to Rifampicin and Fusidic Acid during a further 8 weeks after cultures revealed growth of S. epidermidis. During second stage revision, a hybrid inverse prosthesis with silver coating was implanted, with a total of 20 ml Cerament ™G (injected into the glenoid cavity prior to insertion of the base plate and around the humeral implant-bone interface) and again stabilized with a Trevira tube. Unfortunately, this prosthesis remained unstable, ultimately requiring re-revision to a completely new constrained reverse prosthesis with a custom glenoid shell and silver-coated proximal humeral component. 18 months postoperatively, the patient's shoulder remains pain free and stable, without signs of persistent or reinfection since the initial second stage revision. The function however, unfortunately remains poor. This case report illustrates the application of an antibiotic-eluting bone graft substitute in a specific clinical situation, where co-delivery of an antibiotic together with a bone remodeling agent may be beneficial to simultaneously address PJI as well as poor residual bone quality

An experimental study was performed in order to investigate methods of preparation and mechanical properties of a potential bone graft substitute. This new composite material consists of porous hydoxyapatite coated with oxidised cellulose. Porous hydoxyapatite has excellent osteoconductive properties and promising strength characteristics. Drawbacks include its lack of osteoinductive properties and its brittle nature. Oxidised cellulose can be functionalised to provide binding sites for proteins, drugs and cells, which would allow for increased osteoinductive activity. It has good tensile strength. By creating a composite of these two substances, it was proposed that a graft substitute could be created. Hydroxyapatite samples were formed by processing and sintering bovine cancellous bone. A method was devised by which cellulose was brought into solution and infiltrated into hydoxyapatite samples. The cellulose was then regenerated (cured) and oxidised. Infrared spectrometry confirmed the desired chemical reactions took place and that oxidised cellulose was formed. Scanning electron microscopy confirmed that the three-dimensional structure of the hydroxyapatite was satisfactorily coated. Crush testing showed that infiltrated samples were less brittle and more likely to hold their shape than control samples. Further development and testing is required to assess this composite material for its biological activity and potential as a bone graft substitute

Aim. To investigate the antimicrobial activity of a gentamicin-loaded bone graft substitute (GLBGS) in the prevention and eradication of bacterial biofilms associated with prosthetic joint infections (PJI). Method. The GLBGS (17,5 mg gentamicin/ml paste) with 40% hydroxyapatite/60% calcium sulfate. 1. was tested against biofilms of methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, methicillin-susceptible S. aureus (MSSA) ATCC 29213, Escherichia coli Bj HDE-1, S. epidermidis ATCC 12228 and Enterococcus faecalis ATCC 19433. For prevention studies, glass beads and different combinations of GLBGS were co-incubated for 24h at 37°C in CAMH broth with 1–5 × 10. 6. CFU/mL of bacteria. For eradication, biofilms were formed on glass beads for 24h at 37°C in CAMH broth. Then, beads were incubated with different combinations of GLBGS in medium at 37°C for 24h. For microcalorimetric measurements, beads were placed in ampoules and heat flow (µW) and total heat (J) were measured at 37°C for 24h. The minimal heat inhibitory concentration (MHIC) was defined as the lowest gentamicin concentration reducing the heat flow peak by ≥90% at 24h. Results. The GLBGS showed a good activity against all tested strains in both biofilm prevention and eradication. All MHIC values are reported in Table 1. Lower MHICs were observed when GLBGS was tested against E. coli (9.6 µg/mL prevention and 19.2 µg/mL eradication) and S. epidermidis (86 µg/mL and 38.8 µg/mL, respectively). For both prevention and eradication of MSSA, GLBGS MHIC was 631 µg/mL. E. faecalis biofilm formation was prevented with 631 µg/mL and eradicated with double concentration. MRSA showed a higher resistance to GLBGS up to 2516 µg/mL, both in biofilm prevention and eradication. Conclusions. This GLBGS is a valid composite for the prophylaxis and treatment of PJI. Further studies will be performed to evaluate the activity of higher concentrations of GLBGS against MRSA. 1. CERAMENT™|G, BONESUPPORT AB, Sweden

To assess the performance of calcium sulphate pellets as a bone graft substitute in an Orthopaedic Oncology practice using clinical and radiological outcomes. Between 1998 and 2001, calcium sulphate pellets were used in cavitary defects in 38 procedures in 34 patients with bone tumours. In 29 calcium sulphate pellets were used alone, in 8 allograft and in 1 autograft bone was added. The diagnosis was unicameral bone cyst in 13, giant cell tumour in 11, non-ossifying fibroma in 2, chondroblastoma in 2, benign fibrous histiocytoma in 2 and another pathology in 8 procedures. The femur was involved in 12 procedures, the humerus in 8, the radius in 5, the tibia in 4, the fibula in 3, the calcaneus in 2, and one procedure each in the tarsal cuboid, a metatarsal, the talus, and the middle phalanx of a finger. Median follow up was 14 months (3 to 48). Seven patients had wound complications. Pellets had absorbed completely in 26/28 (93%) evaluable procedures by 3 months. Healing of the defect occurred in 24/28 (86%) evaluable procedures by 6 months. In 6 cases, the healed defect contained cystic areas simulating local recurrence. In 3 cases, there was collapse of the defect. In cavitary defects, calcium sulphate pellets reliably absorb. Some patients have wound complications, especially where the cavity is relatively superficial. The pellets do not provide mechanical stability where there is attenuated cortical bone. Cysts within the healed defect may simulate recurrence

We performed a prospective audit to assess radiological and clinical sequelae of using injectable calcium sulphate in the management of distal radial fractures. All patients in a 4-month period who were treated with injectable calcium sulphate for distal radial fracture were included in the audit. Initial data was collected on demographics; AO classification and degree of deformity; method of fixation and surgical complications. Follow up consisted of clinical and radiological assessment of fracture healing at standard fracture clinic intervals with a final assessment of subjective functional recovery. 16 patients were included in the audit, all of whom were followed up for a minimum of 8 weeks. We observed a low incidence of secondary displacement, and did not observe the problem of increased pain and erythema that has been observed with other bone graft substitutes. We conclude that injectable calcium sulphate is a useful adjunct to conventional management of these fractures that is safe, helps maintain fracture reduction and is not associated with product specific complications

Introduction: Total hip arthroplasty is one of the most frequently performed surgical procedures, with implants usually giving over 90% survival at 10 years. The failure rate is primarily due to aseptic loosening often associated with progressive bone stock loss. Impaction of cancellous morselized allografts with cement can be used for revision total hip arthroplasty in such cases. There is increasing interest in the use of synthetic bone graft substitutes as extenders to allograft due to the shortage and variable quality of allograft. A chemically-pure synthetic calcium phosphate (CaP) allograft extender is compared with allograft alone for acetabular and/or femoral revisions using the Impaction Grafting technique. Methods: 96 hips in 94 patients underwent revision hip arthroplasty using impaction grafting at 4 sites. Hip revision using impaction grafting was carried out using the Exeter X-Change Instrumentation system, using an Exeter Stem and/or a cemented polyethylene cup. Patients were randomized to receive allograft or CaP plus allograft in a 50:50 volume. Clinical and radiographic assessment was conducted pre-operatively and immediately post-operatively and at 6, 12 and 24 months. Clinical assessments included Harris Hip, Oxford and Charnley modified Merle d’Aubigne scores. Clinical complications were also recorded. Radiographs were assessed for the graft quality, radiolucent lines, lyses or migration, and incorporation of graft. The X-rays were also independently reviewed by an experienced author. Results: The mean age was 70.2 years (range 41–89 years) with 58 males and 36 females. A total of 40 femoral revisions and 88 acetabular revisions were conducted. There were 46 patients in the ApaPore group, 49 patients in the allograft group and 1 patient who received CaP/allograft and allograft for an acetabular and femoral revision respectively. No deep infections or adverse events due to the CaP were reported, with no significant difference in complication rates including revision and re-operations. No significant difference in acetabular migration, femoral subsidence, radiolucencies and lyses between the groups was observed. The independent review found no difference between the groups in terms of migration. The bone density was apparently greater for the ApaPore group at 12 months (p=0.001) and 24 months (p=0.012) although the significance of this is unclear. No significant difference in the clinical measures was observed between the groups. Conclusion: CaP is comparable with allograft in terms of performance and safety when used as an allograft extender for total hip revision arthroplasty using impaction grafting

Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration.

Endoprosthetic reconstruction for pathologic acetabular fractures is associated with a high risk of periprosthetic joint infection. In this setting, bone defect reconstruction utilising co-delivery of a synthetic bone substitute with an antibiotic, is an attractive treatment option from both, therapeutic and prophylactic perspective. We wished to address some concerns that remain regarding the possible presence of potentially wear inducing particles in the periprosthetic joint space subsequent to this procedure. We analysed a drain fluid sample from an endoprosthetic reconstruction of a pathologic acetabular fracture with implantation of a gentamicin eluting, biphasic bone graft substitute, consisting of 40% hydroxyapatite (HA) and 60% calcium sulphate (CERAMENT G), into the residual peri-acetabular bone defect. This sample was divided into two 1.5ml subsamples, to one of which 100mg HA particles were added as control before burning off all organic substance at very high temperature. These heat treated samples were then examined with scanning electron microscopy (SEM) and energy dispersive x-ray analysis (EDAX) and compared to a reference sample consisting of HA particles only. On SEM, hydroxyapatite particles were readily recognisable in the control and reference samples, whereas only very few particles over 2μm were apparent in the ”pure” drain sample. EDAX revealed that very large amounts of salts were present in both drainage samples. The pure drainage sample however, contained markedly lower amounts of calcium and phosphate compared to reference and control samples. No HA particles as such, were seen in the pure sample, however their presence cannot be excluded with absolute certainty, as some particles might have been hidden within the large salt conglomerates. We could not find clear evidence that the drain fluid really contained HA particles. More thorough investigations are needed and future analyses with prior removal of the high salt content would likely yield more conclusive results

Aims: The aim of the study is to evaluate the clinical application in veterinary orthopedics of the bone stromal cells loaded on three-dimensional resorbable osteogenic scaffolds. Methods: On the basis of the results obtained after an experimental study on 54 adult sheep (data in process), the Authors have carried out a clinical study on 9 dogs of different breed, age,sized with the different orthopaedic lesion associated to large bone defects (from 2 to 4,8 cm) (bone cyst of glenoid rime, non-union of the tibia and of the femur, osteosarcoma of the radio and the proximal humerus, lenghtening of the radius, bone large defect of the distal radius).With the local anesthesia performed with 2% lidocaine the marrow samples were collected from the iliac crest two hours before the surgery. The bone marrow nucleated cells were then isolated from the bone marrow by gradient centrifugation and loaded on the scaffold on biomaterial, which size and shape was defined before performing the surgery. The cells separated were added with some drops of thrombin. The material used for the study was Osteostim Skelite resorbable bone graft substitute (manufactured by Millenium Biologic Inc-.Canada) which chemical composition and size facilitates the ingrowth of bone. X-ray exams were performed immediately after the surgery. Clinical, ultrasound and x-ray exams were performed after 20 days and then every month. Results: 7 of 9 treated dogs have shown very good clinical and x-ray results. Conclusions: One of the objective of the study was to use the fresh bone stromal cells (BMSCs) in clinical applications in large bone defects in the dog. The advantages of using the cells are: they don’t need to be expanded in vitro, they preserve their osteogenic potential to form bone and promote the proper integration of the implant with bone and lastly, the technique is easier and the costs are lower. We use a fully resorbable biomaterial with BMSCs to obtain a complete substitution of large bone defects since the final goal is the complete substitution of the biomaterial scaffold with new formed bone. Persistency of biomaterial, in fact, limits the complete integration of the two (old and new) interfaces and may represent a weak spot in functionality when tensions and loads are fully applied to the bone, in spite of a satisfactory surgical recovery

Porous collagen-glycosaminoglycan (Col/GAG) scaffolds have previously been used clinically as regeneration templates for peripheral nerves and skin^[1]. For defects involving even minimal load-bearing applications however, these scaffolds do not possess the required stiffness. Calcium phosphates (CaPs) are often used as bone-graft substitutes due to their biocompatibility and direct bone-bonding ability. While CaPs have sufficient stiffness for bone-defect applications, unlike Col/GAG they lack elasticity and are very brittle. Combining these two materials produces a composite with enhanced material properties and chemical similarity to natural bone. The addition of CaP nanocrystallites into the Col/GAG matrix produces a 3-dimensional structure that maintains its structural integrity even when wet. In this study, the in vivo performance of mineralised Col/GAG composites was evaluated by implantation into a six-week ovine bone-defect model.

Four different materials were implanted; Col/GAG alone, Col/GAG with octacalcium phosphate, Col/GAG with hydroxyapatite and Col/GAG with brushite. Implants with a diameter of 9mm and length of 9mm, were placed bilaterally into the distal femoral condyle of the hind legs of thirteen sheep. This site was selected due to the large volume of load-bearing cancellous bone. Cancellous autograft was harvested from the tibial tuberosity and placed in the defect sites of two sheep as a positive control.

All animals were sacrificed after 6 weeks and tissue containing the implants was prepared for histological evaluation. Image analysis of Von Kossa stained sections showed that all mineralised Col/GAG implants had significantly more bone in the implant site than unmineralised Col/GAG but were not significantly different between CaPs. Interestingly, new bone formation often followed the structure of the porous material struts which acted as a template. The defect containing the autograft contained the greatest amount of new bone.

Objective

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

This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery.

Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens.

There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures.