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

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

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

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

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.

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.

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

Introduction. In specific conditions, infection may lead to bone loss and is difficult to treat. 1. Current clinical approaches rely on the introduction of antibiotics. While these may be effective, there are concerns regarding the rise of antimicrobial resistance. There is therefore interest in the development of antimicrobial bone graft substitutes for dental and trauma surgery. Aim & Objectives. The incorporation of zinc into biomaterials has been shown to confer broad spectrum antimicrobial activity, but this has not yet been applied to the development of a commercial bone graft substitute. The aim of this research was therefore to prepare and characterise a series of zinc-substituted nanoscale hydroxyapatite (nHA) materials, including evaluation of antimicrobial activity. Method. Zinc (Zn) substituted nHA materials were prepared (0, 5, 10, 15 & 20 mol.% Zn) using a wet chemical precipitation method with a rapid mixing. (2). The reaction was carried out using zinc hydroxide at pH 10. The suspension formed was washed and dried into both powder & paste forms. The resultant powders were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The antimicrobial activity was evaluated against Staphylococcus aureus (S8650 strain - isolated from an osteomyelitis case), by two techniques. The Miles and Misra method was applied to determine the number of colony-forming units (CFUs) in bacterial suspensions incubated with pastes. Secondly, a biofilm initialization method was used to evaluate the capacity of the materials to prevent biofilm formation. One-way analysis of variance (ANOVA) was used for the statistical analysis and results with p-value < 0.05 were considered statistically significant. Results. XRD indicated the formation of pure hydroxyapatite with up to 10 mol.% Zn without any side products. However, when Zn was increased to 15 & 20 mol %, zinc oxide (ZnO) peaks were detected. The TEM showed nanoscale needle-like particles when Zn was increased compared to nHA particles. Regarding the antibacterial activity, ZnHA pastes at all concentrations caused a significant reduction in bacterial CFUs in a dose-dependent manner (50, 100 & 200 mg). Additionally, even the lowest zinc substitution (5 mol.%) significantly reduced biofilm formation. Conclusion. The results demonstrated a novel method to produce a Zn-substituted nHA that showed antimicrobial activity against a pathogen isolated from a bone infection

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

Allograft materials have been the mainstay in addressing bone deficiencies in knee and hip replacement and revision surgery for decades because of the associated donor site morbidity of autografts. Bone graft substitutes have been developed to address allograft issues including potential contamination, disease transmission, and availability. Although non-autogenous products have no osteogenic potential, they do have a variable degree of osteoinductive and osteoconductive properties. Unfortunately, there are limited reports regarding use of bone graft substitutes for use in total hip and knee arthroplasty. Bone graft substitutes have most frequently been used as an “extender”, in combination with morsellised allograft, to fill cavitary defects. Incorporation of this bone graft substitute and morsellised allograft combination appears to occur incompletely. Stable implant fixation appears to be a prerequisite for incorporation of bone graft substitutes, as these cannot be relied upon for structural support. Although bone graft substitutes appear to perform satisfactorily as “fillers” for contained cavitary bone defects, ultraporous metal augments have become the preferred method of providing structural support for some defects. In view of their substantial cost, high quality clinical, radiographic and retrieval data regarding performance of bone graft substitutes is needed

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately, we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

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

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

In North America, and for the most part globally, a cementless acetabular component with adjuvant screw fixation is the preferred technique for revision total hip arthroplasty. However, there are situations that involve massive pelvic bone loss that preclude the use of a cementless cup alone. Options include: . i). Enhanced fixation components and augments. ii). Specialised constructs (cup/cage). iii). Structural allografts. iv). Bone graft substitutes. Complex acetabular revisions present the arthroplasty surgeon with challenges that require an approach with more than one solution for all scenarios. While structural allografts have recently fallen out of favour with the increasing use of enhanced fixation components, there would still appear to be a role in the case in which bone stock restoration is a primary goal. The role of bone graft substitutes remains unclear, with supportive basic science data, but limited clinical experience to date. An algorithm will be discussed to assist in prioritising the multiple goals of acetabular reconstruction and one stock restoration

Aim. A gentamicin-eluting biocomposite consisting of hydroxyapatite and calcium sulfate. 1. can provide effective dead space management in chronic osteomyelitis. However, radiographic follow-up after implantation of this novel material has consistently shown evidence of several unique imaging features previously not described with other comparable bone graft substitutes. Conclusive interpretation of these newly described imaging features is difficult as long term follow-up and histological correlation is not yet available. The aim of this study was to establish a large animal model, closely simulating the clinical situation in order to permit further analysis of imaging features in correlation with histological progression of bone remodelling. Method. Standardised bone defects were created in ten Merino-wool sheep (age: two to four years). Large drill holes (diameter 2.5cm, depth 2cm, volume approx. 10ml) were placed in the medial femoral condyles of both hind legs and filled with a gentamicin antibiotic eluting bone graft substitute. *. Initially surgery was carried out on the right hind leg. Three months later, an identical intervention was performed on the contralateral side. With sacrifice planned after six or twelve months, bone voids three, six, nine and twelve months post-implantation are obtained for evaluation. The study was approved by the Animal Care Committee of Thuringia, Germany. Results. We present our preliminary radiographic results after a follow-up of six months. The bio-composite was clearly visible on all initial post-operative radiographs, showing intimate contact to the surrounding cancellous bone of the distal femur. At one month, a radio-dense ring around the bone void (the so called “halo sign”) was found in four of six bone voids treated with the biocomposite. From 2 months onwards this “halo” typically appeared to progress towards the centre of the treated defects, where spherical remnants of the composite often become increasingly apparent. This pattern has been termed “marble sign” and often appears in combination with the halo-sign. Between three to six months bone remodelling appears to continue, halo- and marble sign increasingly disappear and the composite becomes more and more indistinct from surrounding cancellous bone. Conclusions. We have established a large animal model, which appears to mimic the clinical situation very well and reproduces comparable radiographic post implantation features previously observed and described in clinical cases (including the “halo” and the “marble” sign). We expect that this model will provide valuable information regarding the correlation between histological and basic & advanced imaging features (including MRI, CT and Dexa scans) in the future

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