Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1

Aim. To determine if systemic toxicity occurs after the use of antibiotic loaded calcium sulphate in the treatment (1) of bone and soft tissue infection. Although antibiotic loaded calcium sulphate is increasingly used for the local treatment of bone and soft tissue infection, there is little data to demonstrate that systemic levels generated by local release of antibiotics are safe. For this reason, we routinely assay systemic levels of antibiotics. Methods. Patients with osteomyelitis or soft tissue infection underwent surgical debridement and lavage of the infected tissue in routine fashion. Patients with osteomyelitis were graded with the Cierny-Mader classification. Bone cavities and soft tissue dead spaces were packed with antibiotic loaded calcium sulphate (10–40 cc) loaded with Vancomycin (1–4 g) and Gentamicin (240–960 mg). The wounds were closed over the antibiotic loaded calcium sulphate. Patients underwent serial assays of Vancomycin and Gentamicin levels on the day of surgery and the first two post-operative days. Renal function was also measured. Results. 12 limbs in 10 patients were treated for osteomyelitis or soft tissue infection. There was 1 Cierny-Mader grade 1, 3 Cierny-Mader grade 3, and 2 Cierny-Mader grade 4. Two had deep soft tissue infection alone. There were 3 type A hosts and 7 type B hosts. The patients age ranged from 24 to 89 (mean 54). In patients without renal dysfunction, the systemic levels were either unmeasurable at the first assay, or below the acceptable trough level. (Mean 2.4 and 1.8 for Vancomycin and Gentamycin respectively). They had unmeasurable systemic levels at the third assay. In patients with renal dysfunction, systemic levels were in the therapeutic range determined for systemically administered antibiotics, but these levels remained high and did not decrease until patients had undergone their routine dialysis. Conclusions. In patients treated with antibiotic loaded Stimulan, antibiotic assays are not necessary in patients who have normal renal function, as they clear the systemic absorption as quickly as it is generated. Patients with impaired renal function should have lower doses of antibiotic used for their topically applied carrier, and should undergo assays regularly to ascertain if levels are remaining below the accepted range determined for systemically administered antibiotics. If they remain high, the antibiotic loaded calcium sulphate could be removed. * Stimulan (Biocomposites, Keele, UK)

Intro. Calcium sulphate (CS) is a recent alternative for antibiotic elution in infected bones and joints. The purpose of this study is to evaluate the use of antibiotic impregnated calcium sulphate (AICS) beads in the management of infected tibia and femur, with regards to patient outcomes and complication rates (including reinfection rate, remission rate and union rate). Methods. Searches of AMED, CINAHL, EMBASE, EMCARE, Medline, PubMed and Google Scholar were conducted in June 2020, with the mesh terms: “Calcium sulphate beads” or “Calcium sulfate beads” or “antibiotic beads” or “Stimulan” AND “Bone infection” or “Osteomyelitis” or “Debridement” AND “Tibia” or “Femur”. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of interventions (ROBINS-i) tool, and quality assessed via the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. Results. Out of 105 relevant papers, 11 met the inclusion criteria for data extraction. Total infection recurrence rate was 6.8% (range 3.2 – 11.9%, n = 295), which was significantly lower (p < 0.001) than that of polymethylmethacrylate (PMMA; 19.6%, n = 163). Complication rates varied. The main issue regarding AICS use was wound drainage (7.9 – 33.3%), which was considerably higher in studies involving treatment of the tibia only. Studies using PMMA did not experience this issue, but there were a few incidences of superficial pin tract infection following surgery. Conclusions. AICS was consistently effective at infection eradication, despite variation in causative organism and location of bead placement. Additionally, PMMA has many inconvenient properties. AICS is therefore an attractive alternative as an adjunct in treatment of infected tibia and femur. Wound drainage rate varied and was higher in studies regarding tibial cases alone

We describe a case series using calcium sulphate bio composite with antibiotics (Cerament/Stimulan) in treating infected metalwork in the lower limb. Eight patients aged 22–74 (7 males, 1 female) presented with clinical evidence of infected limb metal work from previous orthopaedic surgery. Metal work removal with application of either cerement in 5 cases (10–20ml including 175mg–350mg gentamycin) or stimulan in 3 cases (10–20ml including either 1g vancomycin or clindamycin 1.2g or 100mg tigecycline) into the site was performed. Supplemental systemic antibiotic therapy (oral/intravenous) was instituted based on intraoperative tissue culture and sensitivity. Four patients had infected ankle metalwork, 2 patients infected distal tibial metalwork and 2 had infected external fixators. Metal work was removed in all cases. The mean pre operative CRP was 15.8mg/l (range 1–56mg/l). The mean postoperative CRP at 1 month was 20.5mg/l (range 2–98mg/l). The mean pre op WCC was 7.9×10. 9. (range 4.7–10.5 ×10. 9. ). Mean post op WCC at 1 month was 7.1×10. 9. (range 5.0–9.2×10. 9. ). The organisms cultured included enterobacter, staphylococcus aureus, staphylococcus epidermidis, staphylococcus cohnii, stenotrophomonas, acinetobacter, group B streptococcus, enterococcus and escherichia coli. No additional procedures were required in any case. All surgical wounds went on to heal uneventfully. Infection control and union was achieved both clinically and radiologically in all cases. Our results support the use of a calcium sulphate bio composite with antibiotic as an adjuvant for effective local infection control in cases with implant related bone sepsis. The technique is well tolerated with no systemic or local side effects. We believe that implant removal, debridement and local antibiotic delivery can minimise the need for prolonged systemic antibiotic therapy in such cases

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them

A number of techniques have been developed to improve the immediate mechanical anchorage of implants for enhancing implant longevity. This issue becomes even more relevant in patients with osteoporosis who have fragile bone. We have previously shown that a dynamic hip screw (DHS) can be augmented with a calcium sulphate/hydroxyapatite (CaS/HA) based injectable biomaterial to increase the immediate mechanical anchorage of the DHS system to saw bones with a 400% increase in peak extraction force compared to un-augmented DHS. The results were also at par with bone cement (PMMA). The aim of this study was to investigate the effect of CaS/HA augmentation on the integration of a different fracture fixation device (gamma nail lag-screw) with osteoporotic saw bones. Osteoporotic saw bones (bone volume fraction = 15%) were instrumented with a gamma nail without augmentation (n=8) or augmented (n=8) with a CaS/HA biomaterial (Cerament BVF, Bonesupport AB, Sweden) using a newly developed augmentation method described earlier. The lag-screws from both groups were then pulled out at a displacement rate of 0.5 mm/s until failure. Peak extraction force was recorded for each specimen along with photographs of the screws post-extraction. A non-parametric t-test was used to compare the two groups. CaS/HA augmentation of the lag-screw led to a 650% increase in the peak extraction force compared with the controls (p<0.01). Photographs of the augmented samples shows failure of the saw-bones further away from the implant-bone interface indicating a protective effect of the CaS/HA material. We present a novel method to enhance the immediate mechanical anchorage of a lag-screw to osteoporotic bone and it is also envisaged that CaS/HA augmentation combined with systemic bisphosphonate treatment can lead to new bone formation and aid in the reduction of implant failures and re-operations

Majority of osteoporosis related fractures are treated surgically using metallic fixation devices. Anchorage of fixation devices is sometimes challenging due to poor osteoporotic bone quality that can lead to failure of the fracture fixation. Using a rat osteoporosis model, we employed neutron tomography and histology to study the biological effects of implant augmentation using an isothermally setting calcium sulphate/hydroxyapatite (CaS/HA) biomaterial with synthetic HA particles as recruiting moiety for systemically administered bisphosphonates. Using an osteoporotic sawbones model, we then provide a standardized method for the delivery of the CaS/HA biomaterial at the bone-implant interface for improved mechanical anchorage of a lag-screw commonly used for hip fracture fixation. As a proof-of-concept, the method was then verified in donated femoral heads and in patients with osteoporosis undergoing hip fracture fixation. We show that placing HA particles around a stainless-steel screw in-vivo, systemically administered bisphosphonates could be targeted towards the implant, yielding significantly higher peri-implant bone formation compared to un-augmented controls. In the sawbones model, CaS/HA based lag-screw augmentation led to significant increase (up to 4 times) in peak extraction force with CaS/HA performing at par with PMMA. Micro-CT imaging of the CaS/HA augmented lag-screws in cadaver femoral heads verified that the entire length of the lag-screw threads and the surrounding bone was covered with the CaS/HA material. X-ray images from fracture fixation surgery indicated that the CaS/HA material could be applied at the lag-screw-bone interface without exerting any additional pressure or risk of venous vascular leakage.: We present a new method for augmentation of lag-screws in fragile bone. It is envisaged that this methodcould potentially reduce the risk of fracture fixation failure especially when HA seeking “bone active” drugs are used systemically

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

There is a lack of carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotic for Staphylococcus aureus deep bone infections (DBIs). RIF is also associated with systemic side effects, and known for causing rapid development of antibiotic resistance when given as monotherapy. We evaluated a clinically usedbi-phasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). It was hypothesized that this combined approach could provide improved biofilm eradication and prevent the development of RIF resistance. Methods: 1) Biofilm eradication: Using a modified crystal violet staining biofilm quantification method, the antibiotics released at different time points (Day 1, 3, 7, 14, 21, 28 and 35) from the hemispherical pellets of CaS/HA(500 mg)-VAN (24.57 mg) / GEN (10.35 mg) composites with or without RIF (8.11 mg) were tested for their ability to disrupt the preformed 48-h old biofilms of S. aureus ATCC 25923, and S. aureus clinical strain P-3 in 96-well microtitre plate. For each tested group of antibiotic fractions, five separate wells were used (n=5). 2) Testing for resistance development: Similar to the method mentioned above the 48-h biofilm embeded bacteria exposed to antibiotic fractions from different time points continuously for 7 days. The biofilms remained were then tested for RIF resistant strains of bacteria. Overall, there was clear antibiofilm biofilm activity observed with CaS/HA-VAN/GEN+RIF combinations compared with CaS/HA-VAN/GEN alone. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with combinations of CaS/HA-VAN/GEN+RIF. Enhanced antibiofilm effects without development of RIF resistance indicates that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for additional local delivery in clinically demanding DBIs. Acknowledgement: We deeply acknowledge the Royal Fysiographic Society of Lund, Landshövding Per Westlings Minnesfond and the Stina and Gunnar Wiberg fond for financial support

Targeted delivery of drugs is a major challenge in diseases such as infections and tumors. The aim of this study was to demonstrate that hydroxyapatite (HA) particles can act as a recruiting moiety for various bioactive molecules and as a proof-of-concept demonstrate that the affinity of drugs to hydroxyapatite can exert a biological effect. A bisphosphonate, zoledronic acid (ZA), was used as a model drug. Experiment 1 (ZA seeks HA): Calcium sulphate (CaS)/hydroxyapatite (HA) biomaterial pellets (diameter¸=5 mm, height=2 mm) were implanted in the abdominal muscle pouch of rats. After 2-weeks of implantation, a sub-cutaneous injection of 14C-ZA (0.1 mg/kg) was given. 24 h later, the animals were sacrificed and the uptake of ZA determined in the pellets using scintillation counting. Experiment 2 (Systemically administered ZA seeks HA and exerts a biological effect): A fenestrated implant was filled with the CaS/HA biomaterial and inserted in the proximal tibia of rats. 2-weeks post-op, a subcutaneous injection of ZA (0.1 mg/kg) was given. Animals were sacrificed at 6-weeks post-op. Empty implant was used as a control. Peri-implant bone formation was evaluated using different techniques such as micro-CT, mechanical testing and histology. Welch's t-test was used for mechanical testing and Mann-Whitney U test for micro-CT data analysis. Experiment 1: Uptake of radioactive ZA in the CaS/HA biomaterial was confirmed. Almost no ZA was present in the surrounding muscle. These results show high specific binding between systemically administered ZA and synthetic particulate HA. Experiment 2: Significantly higher peri-implant bone was measured using micro-CT in the group wherein the implant contained the CaS/HA biomaterial and ZA was administered systemically (This study presents a method for biomodulating HA in situ by different bioactive molecules. The approach of implanting a biomaterial capable of recruiting systemically given drugs and thereby activate the material is novel and may present a possibility to treat bone infections or tumors

Background. With promising antibiofilm properties, rifampicin is considered as a cornerstone in the complementary treatment of bone and joint infections. But, achieving an adequate concentration of rifampicin long-term in bone tissue is a challenge. Long-term systemic administration also comes with concomitant side effects. Thus, local delivery of rifampicin in a carrier to ensure the high local concentration of antibiotic in surgical site after intervention due to infection could be a valuable alternative. However, an ideal platform for local delivery of rifampicin is still lacking. A calcium sulphate/hydroxyapatite (CaS/HA) (Cerament, Bonesupport AB, Sweden) biomaterial was used as a local delivery platform. Here we aimed 1) to evaluate the injectability of CaS/HA hand-mixed with rifampicin at various concentrations up to maximum one daily dose used systemically in clinical practice 2) to test a clinically used and commercially available mixing device containing the biphasic ceramic with rifampicin. Materials & Methods. Three different concentrations (100 mg, 300 mg and 600 mg) of rifampicin powder (Rifampicin Ebb, Sanofi S.P.A, Italy) diluted in 5 mL of mixing solution (C-TRU, Bonesupport AB, Sweden) were used. Rifampicin solution was mixed to the CaS/HA powder and the injectability of the CaS/HA plus rifampicin composite was evaluated by extruding 250 µL of paste manually through a graduated 1 mL syringe connected to an 18G needle (Ø=1.2 mm, L=4 cm). Mixing was done with a spatula for 30 s at 22°C ±1°C. Total weight of the paste before and after extrusion were measured. To normalize the amount of composite that remained in the needle and syringe tip after injection, the mean of the paste extruded from the syringe at 3 min was calculated for the tested concentrations (normalized value). Injectability (%) was calculated by dividing the weight of the paste extruded from the syringe with normalized value. Each test was repeated for three times at various time points (3, 5, 7 and 9 min). Additionally, 300 mg rifampicin was chosen to mix with the CaS/HA in a commercially available mixing system, which is used clinically. Results. All three combinations of CaS/HA plus rifampicin (100 mg, 300 mg & 600 mg) could be completely extruded from 1 mL syringes at 3 min. At 5 min, 100 mg & 300 mg could still be injected, whereas 600 mg was uninjectable or solidified. At 7 min, rifampicin 100 mg & 300 mg showed 34% and 11% of injectability respectively. At 9 min, no injectability was observed. The material was completely set within 15 minutes with all concentrations. With commercial mixing system, at the recommended injection time of 4 min, 78% of the CaS/HA plus rifampicin (300 mg) composite could be injected. Conclusions. The injectability was reduced with the increasing concentration of rifampicin. CaS/HA plus rifampicin (100 mg and/or 300 mg) could be used by hand mixing and transferred to a syringe or by using an available mixing system containing the ceramic. For higher concentrations of rifampicin, the rheological properties of the ceramics have to be modified for injectability

Nitrogen-containing bisphosphonates such as Zoledronic Acid (ZA) are used clinically for the treatment of skeletal diseases related with increased bone resorption. The gold standard is to administrate the drug through a systemic pathway, however this is often associated with high dosages, risk of side-effects, reduced site-specific drug delivery and hence, limited drug-effectiveness. A controlled local drug delivery, via a biomimetic bone graft, could be beneficial by direct and time-regulated application of significantly lower drug dosage at the site of interest. Thus, higher efficacy and reduced side-effects could be expected. In this experimental in vivo study, we examined the effect of ZA when used together with a Calcium Sulphate/Hydroxyapatite biomaterial in a femoral condyle bone defect in rats and compared local to systemic administration. The following groups were used: group1: empty defect (no biomaterial & no treatment), group2: biomaterial alone, group3: biomaterial + systemic ZA (0.1mg ZA/kg – single subcutaneous injection), group4–6: biomaterial conjugated with ZA at different concentrations, (0.07 to 0.70 mg ZA/mL of paste, corresponding to 0.0024 to 0.024 mg ZA/kg). The animals were sacrificed at 6 weeks and toxicological examination was performed. Bone regeneration was evaluated using qualitative and quantitative micro-CT analysis and Histomorphometry. The results showed a significant difference between the groups, suggesting that ZA has an overall effect on bone healing. The most pronounced effect was seen with the local application of approximately 10 times less ZA-dosage when compared to systemic use (p<0.001). This study demonstrates the importance of local ZA administration in bone regeneration

Background. The doses of local rhBMP-2 in commercially available materials are high with known drawbacks such as inflammation and premature bone resorption. The latter can be prevented by adding bisphosphonates like zoledronic acid (ZA) but systemic ZA has side effects and patient adherence to treatment is low. In a recent study, we have shown that local co-delivery of rhBMP-2 and ZA via a calcium sulphate/hydroxyapatite (CS-HA) biomaterial can be used to regenerate both cortical and trabecular bone in a rat model of metaphyseal bone defect. Even low doses of local ZA in the biomaterial showed promising results and increased bone formation within the defect compared to the controls. A step before clinical translation of the local treatment regimen is to evaluate the in-vivo release kinetics of these additives and thus in this study, we aimed to investigate the in-vivo pharmacokinetics of rhBMP-2 and ZA from the CS-HA biomaterial in a rat abdominal muscle pouch model over a period of 4-weeks. Methods. In-vivo release kinetics of 125I labeled rhBMP-2 and 14C labeled ZA was performed using an abdominal muscle pouch model in rats (n=6). Both rhBMP-2 and ZA were labeled commercially with a radiochemical purity of >95%. The detection of 125I -rhBMP-2 release was performed by implanting pellets of the CS-HA biomaterial containing 125I -rhBMP-2 and ZA and the same animals followed over a period of 4-weeks (day 1, 3, 7, 14, 21& 28) using SPECT imaging. Similarly, the 14C-ZA was detected by implanting CS-HA pellets containing rhBMP-2 and 14C-ZA. Release was detected via scintillation counting and at each time point (Day 1, 7, 14& 28) 6-animals were sacrificed. Results. BMP Release. The CS-HA biomaterial retained 95±11% after 3-days, 88±12% after a week, 66±9% after 2 weeks, 51±5% after 3 weeks and 43±7% of 125I labeled rhBMP-2 after 4-weeks in-vivo (SPECT-CT). ZA Release. The CS-HA biomaterial retained 89±14% after a week, 84±8% after 2 weeks, 83±9% after 3 weeks and 77±3% of 14C labeled ZA after 4 weeks of in-vivo implantation. Discussion. Improved carriers and better knowledge of the release might improve the effect of bone active drugs in orthopedics. Our previous study shows that an off-the-shelf ceramic biomaterial combined with ZA alone or with both rhBMP-2 and ZA can be used to regenerate bone with potential for clinical translational. This study demonstrates long-term co-delivery of both rhBMP-2 and ZA in-vivo via the biomaterial. Constant availability of rhBMP-2 over a long period of time can give osteoinductive properties to the material while presence of local ZA prevents premature bone loss. The pharmacokinetic release pattern differs from what we have reported in vitro with less BMP and more ZA being released in vivo during the first 4 weeks. We speculate that rapid protein passivation of the ceramic material slows the release of BMP and partly preventing the ZA binding to apatite

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

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed. . In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups. After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate. Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes. Cite this article: Bone Joint J 2014; 96-B:845–50

An injectable material consisting of calcium sulphate mixed with hydroxyapatite was investigated as a possible alternative to autograft in the restoration of bone defects. The material was studied both in vitro in simulated body fluid (SBF) and in vivo when implanted in rat muscles and into the proximal tibiae of rabbits. Variation in the strength and weight of the material during ageing in SBF was measured. Tissue response, material resorption and bone ingrowth were studied in the animal models. A good tissue response was observed in both the rat muscles and rabbit tibiae without inflammatory reactions or the presence of fibrous tissue. Ageing in SBF showed that during the first week carbonated hydroxyapatite precipitated on the surfaces of the material and this may enhance bone ingrowth

We used a goat model of a contaminated musculoskeletal defect to determine the effectiveness of rapidly-resorbing calcium-sulphate pellets containing amikacin to reduce the local bacterial count. Our findings showed that this treatment eradicated the bacteria quickly, performed as well as standard polymethylmethacrylate mixed with an antibiotic and had many advantages over the latter. The pellets were prepared before surgery and absorbed completely. They released all of the antibiotic and did not require a subsequent operation for their removal. Our study indicated that locally administered antibiotics reduced bacteria within the wound rapidly. This method of treatment may have an important role in decreasing the rate of infection in contaminated wounds.

Objectives

Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis.

Objectives

To explore the therapeutic potential of combining bone marrow-derived mesenchymal stem cells (BM-MSCs) and hydroxyapatite (HA) granules to treat nonunion of the long bone.

Objectives

The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation.