Background. Calcium sulfate and phosphate have a long clinical history of use as bone-void fillers (BVF) with established biocompatibility and resorption profiles. It has been widely reported that the addition of ‘impurity’ elements such as Silicon, Strontium and Zinc to calcium phosphate is advantageous, resulting in an improved bone healing response. Methods. This study examined the in vivo response of two formulations of calcium sulfate, as 3mm diameter hemispherical beads, in critical sized defects created in cancellous bone of distal femur and proximal tibia (10mm diameter × 13mm depth) in adult sheep; beads prepared from recrystallised pharmaceutical grade calcium sulfate (RPCS, Stimulan, Biocomposites Ltd, UK) and a lower purity medical grade material containing 1% strontium (SrCS). The animals were sacrificed at 3, 6 and 12 weeks post implantation and the surgical sites analysed using microCT and decalcified histology. Results. Radiographic analysis showed a slower resorption for SrCS compared to RPCS. Radiographic analysis for both materials confirmed little residual beads at three weeks post implantation. Radiographs at sacrifice confirmed no adverse reactions at any sites at 3, 6 and 12 weeks. Radiographic data alone was not adequate to determine the status of the bone formation and the implant resorption at the implant site. Histological analysis confirmed little or no adverse tissue reactions to either material. However, RPCS outperformed the modified material in terms of new bone formation at all time points post implantation. At 3 weeks histology for RPCS confirmed that residual beads were still visible with active new bone growth appearing to penetrate centripetally into the defect with some resorption of the implant material. By 6 weeks significant new bone was present throughout the defect. In comparison, absorption of the modified material was slower, and penetration of new bone into the defect was less progressed. Conclusions. The rapid bone regenerative ability of the recrystallised pharmaceutical grade calcium sulfate was demonstrated. The presence of 1% Strontium impurity acted to delay implant absorption and bone healing in this model

Daptomycin has a unique mechanism of action against Gram-positive bacteria. Daptomycin is only bactericidal in the presence of calcium ions. [1]. Kanellakopoulou et al [2] investigated elution of daptomycin from calcium sulfate. The results indicated above MIC elution concentrations out to 28 days. Experience reports that the ability for calcium sulfate to set hard when combined with daptomycin can be problematic.[3] This study aimed to investigate the combination of daptomycin with a synthetic recrystallised form of calcium sulfate and investigate zone of inhibition (ZOI) testing against susceptible organisms. 6mm hemispherical beads, were prepared using a commercially available calcium sulfate hemihydrate powder (CSH) – CaSO4 ·1/2H2O. [4] In order to combine daptomycin [5] with the CSH and enable it to set hard, 7mls of saline solution was added to 20g CSH powder and mixed for 80 seconds to initiate the setting reaction. Then 1g of daptomycin powder was added and mixed for a further 30 seconds. The resultant paste was applied to a bead mat and allowed to set. Tryptone soya agar plates were seeded with 0.2ml of a 10e6 – 10e8 cfu/ml suspension of the relevant organism. The plates were incubated at 33 °C ± 2 °C for 30 minutes. The plates were then removed from the incubator and the beads placed on the surface. The plates were then incubated at 33 °C ± 2 °C for 24 hours before examination for the absence of growth as seen by a clear zone around the test sample. Triplicate samples were tested against Staphylococcus epidermidis, Staphylococcus aureus, MRSA, VRE Enterococcus faecium and Propionibacterium acnes. Repeat tests were carried out for beads that had been stored at 37 °C for 21 days to simulate in-vivo conditions. Setting times for the CSH/daptomycin beads were approximately 20 minutes. ZOIs indicating efficacy were seen for all samples both ‘fresh’ and ‘incubated’ with MRSA and Propionibacterium acnes having the largest ZOIs at 31–33mm. A mixing protocol was established to enable set beads to be formed with daptomycin loaded calcium sulfate. As assessed by ZOI testing, the eluted antibiotic maintained efficacy against susceptible pathogens. Results obtained in-vitro may not be indicative of in-vivo performance

Aim. Multispecies biofilms are associated with difficult periprosthetic joint infections (PJI), particularly if they have different antibiotic sensitivities. We aimed to determine if we could generate and kill a multispecies biofilm consisting of a Gram negative and Gram positive pathogen in-vitro with antibiotic loaded calcium sulfate beads containing single or combination antibiotics. Methods. To establish whether we could co-culture mixed species biofilms various combinations of Pseudomonas aeruginosa (PA), Enterococcus faecalis (EF), Staphylococcus aureus (SA) and Enterobacter faecalis (EF) were grown together on 316L stainless steel coupons and agar plates. Based on this screen we focused on PA + EF and challenged them with high purity calcium sulfate beads (Stimulan Rapid Cure) loaded with vancomycin (V), alone tobramycin (T) alone or vancomycin and tobramycin in combination (V+T). Bioluminescence, light imaging, plate count, confocal microscopy and scanning electron microscopy were used to quantify growth. Results. On 316LSS the V loaded bead reduced both EF and PA by approximately 2 logs compared to unloaded control beads. A T alone loaded bead eliminated PA from the dual species biofilm and caused a 2-log reduction in EF. The V+T-beads reduced PA by 9-logs and EF by 8.3 logs. In terms of total CFUs V+T beads reduced the bioburden by 8.4 logs compared to V or T alone. which resulted in 2.1 and 2.6 log reductions respectively. (* P<0.05, *** P<0.001). On agar PA dominated the culture for the unloaded and V loaded beads. However, when challenged with a T loaded bead both species were able to coexist and a zone of killing was generated in both species in the multispecies biofilms. However, this zone was smaller and included more tolerant variants than the zone generated by V+T-loaded beads. Conclusions. There were species proportion differences between biofilms grown on agar and 316LSS demonstrating the importance of growth conditions on species interactions. Antibiotics against strains with differing sensitivities can shift species interactions. High purity calcium sulfate beads containing tobramycin a broad-spectrum Gram positive and negative antibiotic vancomycin, a Gram-positive targeted antibiotic killed a larger percentage of a multispecies in an in-vitro biofilm than either single gram-specific antibiotic alone, demonstrating the advantage of using combination antibiotics for treating multispecies biofilms

The purpose of the study was to evaluate the outcome of curettage and grafting with calcium sulfate pellets for progressive retroacetabular osteolysis with retention of the acetabular component. Seven patients who underwent the procedure were evaluated clinically and radiographically at an average follow-up time of fifteen months. There was no progression of osteolysis following curettage and grafting with good to excellent osseo-integration. All patients had a good functional outcome with no pain during follow-up. Curettage and synthetic grafting of retroacetabular cysts with calcium sulfate pellets is a viable option in halting the progression of retroacetabular lysis and promoting osseous recovery. The purpose of this study was to evaluate outcome of curettage and grafting of progressive retroacetabular osteolysis with calcium sulfate pellets and retention of components. Restoration of retroacetabular bone stock by curettage and grafting with synthetics would obviate the need for autogenous bone graft and its associated risks. Retention of well-fixed acetabular components also aids in prevention of further bone loss associated with component extraction. We conducted a clinical and radiographic review of seven patients who presented to the senior author with radiographic findings of progressive retroacetabular osteolysis. All patients were treated with curettage and filling of the defects with calcium sulfate. Mean follow-up time is fifteen (five to twenty-seven) months. Polyethylene wear was noted in all cases. The size of the lesions ranged from 3.1 x 2.0 to 9.0 x 5.3 cm. On follow-up evaluation, there was no recurrence or progression of the lesions. Osseo-integration was excellent in four cases and good in three cases. All patients had returned to normal level of function with no pain. Patients with retroacetabular osteolysis are often asymptomatic until catastrophic failure occurs as a result of extensive bone loss. Treatment of retroacetabular osteolysis in the setting of well-fixed components is controversial. Retention of the components, curettage and synthetic grafting with calcium sulfate is a viable option to prevent progression of lysis and stimulate bone formation. Curettage and grafting of progressive retroacetabular osteolysis with calcium sulfate and retention of components results in good osseo-integration of the graft and halts the progression of lysis

Aim. Treatment principles of chronic osteomyelitis include debridement, clean sampling, excision of dead bone, stabilization, dead space management, soft tissue closure and systemic antibiotic therapy. Dead space management becomes very complicated, if the bone infection is caused by multi-resistant bacteria. The aim of this investigation was to evaluate the effect of a new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. in the treatment of chronic osteomyelitis (OM) caused by multi-resistant bacteria. Method. From June 2015 to November 2015, 7 patients (4 males, 3 females, average age 52.6y) were treated according to the above mentioned principles using the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. Infections were caused by methicillin-resistant Staphylococcus aureus (MRSA), multi-resistant Staphylococcus epidermidis (MRSE) and polymicrobial, vancomycin-sensitive bacteria. We used a two-stage protocol with debridement, excision of bone and external stabilization in the first stage, followed by bone defect reconstruction. To fill the residual bone defects, in 3 patients the new vancomycin-loaded hydroxyapatite / calcium sulfate composite. *. (10mL) was used on its own and in 4 patients combined with 18mL of an unloaded calcium sulfate / hydroxyapatite composite. **. Post-operative follow-up was evaluated clinically and by radiographs and CT scans at 6, 14 and 24 weeks. Results. In 6 of 7 patients rapid control of infection was achieved. Soft tissue reactions and prolonged white wound drainage (caused by calcium sulfate dissolution) was seen in 3 of 7 patients. In 6 of 7 patients recurrence of infection has not been observed so far. Radiographs showed different elution intervals of the radiocontrast agent (Iohexol), depending on anatomical location. Bone remodelling or replacement of the composite by new bone was not uniform in the patients and showed specific radiographic signs. In addition to the so-called „puddle sign“, we found septae, membranes, vacuoles and sometimes arc-like structures. Therefore, we suggest the name “arc-sign” for these formations. Conclusions. During the follow-up of the first 7 patients treated with the unloaded calcium sulfate / hydroxyapatite composite. **. in 6 of 7 cases no recurrence of infection was observed. This is very promising in the difficult situation of bone infections caused by multi-resistant bacteria. Follow-up radiographs and CT-scans showed specific patterns during the resorption of the composite and the formation of new bone, which have not been described in other bone graft substitutes so far. The bone defects are not completely filled yet, but the affected bones are clinically stable and patients can ambulate with full weight bearing

Aim. Infection rates after revision THA vary widely, up to 12%. In countries that use antibiotic-loaded cemented stems in combination with perioperative IV antibiotics, infection rates in registry studies are lower. In many countries, however, cementless revision implants are preferred. Our aim was to apply an antibiotic-loaded calcium sulfate coating to cementless revision stems to reduce periprosthetic joint infection (PJI). This study sought to answer two questions: 1) Does the coating of cementless revision stems with calcium sulfate inhibit osteointegration in THA? 2) Does the antibiotic-loaded calcium sulfate coating of revision stems reduce the incidence of PJI?. Method. From Dec. 2010 to Dec. 2015, 111 consecutive revision femoral stems were coated with commercially pure calcium sulfate. 10cc of calcium sulfate was mixed with 1g of vancomycin powder and 240mg of tobramycin liquid and applied to the stem in a semi-firm liquid state immediately prior to stem insertion. The results are compared to a designated control cohort (N=104) performed across the previous 5 years. The surgical methods were comparable, but for the stem coating. All patients were staged preoperatively using the Musculoskeletal Infection Society Staging System and followed for at least 1 year. Results. In the study group of coated stems, there were 46 A hosts, 56 B hosts, and 9 C hosts. In the control group, there were 45 A hosts, 52 B hosts, and 7 C hosts. Both cohorts had 0 cases of aseptic loosening. The overall rate of PJI in the study cohort was 2.7%. Of the 111 revisions, 69 were aseptic (PJI=1.4%) and 42 were second stage revisions for infection (PJI=4.8%). PJI occurred in 2.2% of A hosts, 1.8% of B hosts, and 11.1% of C hosts. In the control cohort, the overall rate of PJI was 7.7%. Of the 104 revisions, 74 were aseptic (PJI=1.4%) and 30 were second stage revisions for infection (PJI=23.3%). PJI occurred in 6.7% of A hosts, 5.8% of B hosts, and 28.6% of C hosts. The results show a reduction in PJI from 7.7% in the control group to 2.7% in the study group and were found to be statistically significant at p-value<0.1 (p=0.09). Conclusions. The application of antibiotic-loaded calcium sulfate to cementless revision femoral stems does reduce PJI. Importantly, this coating did not inhibit osteointegration of the femoral stem. The reduced infection rate in this study supports the concept that bacteria frequently contaminate and reside within the femoral canal

Purpose. Infections in orthopaedic surgery are costly, debilitating complications. The search for new treatments and prevention strategies has led to the use of antibiotic-filled calcium sulfate (CaS) as a bone void filler that is both safe and effective. The purpose of this study was to examine the available data on the efficacy of this technology. Methods. A literature search was performed for studies that evaluated the use of antibiotic-loaded CaS cement in orthopaedics published between inception of the databases to 2017. Selected studies included randomized controlled trials (RCTs) and observational studies published in the English language that met the following criteria: 1) patients underwent an orthopaedic procedure; 2) CaS cement with an antibiotic was used; and 3) at least one of our outcomes were mentioned. Outcomes included resolution of infection, complications related to treatment, subsequent surgeries, overall infection rate, fracture union rate, clinical outcomes, and wound complications. A total of 17 studies were included. Results. Ten studies examined the use of antibiotic-eluting CaS cement with surgical debridement to treat osteomyelitis and reported resolution rates ranging from 80–100%. Two studies examined CaS for prophylaxis of infection after open fracture, with subsequent infection rates ranging from 0–22%. Two studies examined infected non-unions with CaS used as an adjunct to surgery with an 87.5% infection clearance rate. Finally, three studies examined the use of local antibiotic release from CaS in the repair of infected TKAs or THAs, with success rates ranging from 52–93.3%. Conclusion. Initial results support the use of CaS with surgical debridement for osteomyelitis and infected non-unions. Results are mixed for CaS use in the prophylaxis of infection after open fractures and for PJIs, thereby necessitating further research. Overall the studies were small, retrospective, and lacked controls. Further research should focus on RCTs to minimize bias and investigate for non-inferiority. For any figures or tables, please contact authors directly

Aim. To evaluate the clinical outcome of a new absorbable, gentamycin loaded calcium sulfate/hydroxyapatite biocomposite (CERAMENT. ™. /G) as cavity filler after debridement and removal of infected metalwork in chronic osteomyelitis. Methods. We report the retrospective study of prospectively collected data from 36 patients with chronic osteomyelitis from implant infection. Treatment included a single stage protocol with removal of the metalwork, debridement augmented with application of CERAMENT. ™. /G, stabilization, culture-specific antibiotics and primary skin closure or flap. The biocomposite was used for dead space filling after resection of Cierny-Mader (C-M) stage III and IV chronic osteomyelitis. Data were collected on patient age, comorbidities, operation details, microbiology, postoperative complications and type of fixation or plastic surgery. Primary measure of outcome was recurrence rate. Results. According to the C-M classification 22 patients (63%) were defined as Type III and 13 (37%) as Type IV. A total of 26 (72%) patients were Class B hosts. In 9 cases (25%), there was an infected non-union and 1 patient had septic arthritis. Mean age was 52 years (range 22 to 81). Patients were followed for a mean of 20 months (range 6 to 36). Infection was eradicated in 32 patients. There were three (8.3%) recurrences (two cases of osteomyelitis and one of soft tissue/flap infection). Two of them were successfully managed with repeat surgery (one Class B and one Class A host) and one (Class B host) with suppressive antibiotic therapy as per patient's choice. In one infected nonunion the infection was eradicated but the nonunion persisted. Thirteen patients (36.6%) had a local or free fascio-cutaneus flap. Staphylococci (50%) and Enterococci (15%) were the most common microorganisms. Pseudomonas aeruginosa was more common in polymicrobial infection usually with Staphylococcus aureus. Conclusions. A multidisciplicary approach including augmented debridement with CERAMENT. ™. /G is effective for treatment of chronic osteomyelitis with infected metalwork

Introduction. Calcium sulfate bone void fillers (CS-BVF) are increasingly being used for dead space management in infected arthroplasty revision surgery. The use of loose beads of CS-BVF close to the articulating surfaces of an implant means there is potential for them to migrate between the articulating surfaces acting as a third body particle. The aim of this study was to investigate the influence of CS-BVF on the third body wear of total knee replacements. Methods. The influence of CS-BVF on wear was investigated using the commercially available CS-BVF ‘Stimulan’ (Biocomposites Ltd., UK) and posterior stabilised U2 total knee replacement system implants (United Orthopaedic Corp., Taiwan). The experimental wear simulation was performed using a six station ProSim electropneumatic knee simulator (Simulation Solutions, UK) running the Leeds intermediate kinematics input profile [1]. To investigate the damage that could be caused by the third body particles, 5cc of CS-BVF beads (excess) were placed on the tibial component of the implant, the simulator was run dry for 60 cycles before adding lubricant (25% bovine serum supplemented with 0.03% sodium azide) and running for an additional 115,000 cycles representative of the 6–8 weeks the CS-BVF are present in the body prior to their resorption. The surface topography of the cobalt chrome femorals was analysed using contacting profilometry to ascertain whether the third body particles of CS-BVF had damaged the surfaces. To investigate the influence of CS-BVF on the third body wear of the UHMWPE tibials, 3 million cycles (MC) of wear simulation was subsequently carried out. The wear of the UHMWPE tibials was assessed gravimetrically and the wear of implants tested with CS-BVF was compared to the wear against negative controls (initial Ra∼0.02µm) and positive controls (initial Ra ∼0.4µm) damaged with a diamond stylus. N=6 was completed for each condition, statistical analysis was carried out using ANOVA with significance taken at p<0.05. Results. Light scratching was visible on the surface of the cobalt chrome femorals after the implants were challenged with the CS-BVF, however, there was no significant difference (p>0.05) between the surface roughness of the negative controls and those challenged with CS-BVF for any of the roughness parameters of interest (Table 1 & Figure 1). 3MC of wear simulation showed no significant difference (p>0.05) between implants subjected to the third body wear protocol and the negative controls (Figure 2). To significantly increase the wear of the UHMWPE tibials, the damage to the cobalt chrome femorals had to be above a threshold as in the positive controls scratched with a diamond stylus. Conclusions. This study showed that the CS-BVF ‘Stimulan’ had no influence on the third body wear or surface topography of total knee replacements compared to negative controls. Therefore, when used close to articulating surfaces of a metal-on-polyethylene joint replacement, CS-BVF may not influence the wear of an implant or be detrimental to its longevity

Aim. Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin resistant Enterococci (VRE) have emerged as multi-drug resistant Gram-negative pathogens associated with Periprosthetic Joint Infections (PJI). In this study, we evaluated the efficacy of antibiotic-loaded calcium sulfate beads (ABLCB) to inhibit bacterial growth, biofilm formation and eradicate preformed biofilms of K. pneumoniae and E. faecalis. Method. Three strains of K. pneumoniae (carbapenem resistant BAA1705, New Delhi metallo-beta-lactamase producing BAA2146 [NDM-1], a carbapenemase producing BAA2524) and a vancomycin resistant strain of E. faecalis (ATCC51299) were used. 4.8mm diameter ABLCBs (Stimulan Rapid Cure, Biocomposites) were loaded with vancomycin (VAN) & gentamicin (GEN) at 500 and 240 mg/10cc pack or VAN & rifampicin (RIF) at 1000 and 600 mg/10cc pack respectively and placed onto tryptic soy agar (TSA) plates spread with each of the four strains independently and incubated for 24 hours at 37°C. The beads were transferred daily onto fresh TSA medium spread with the test cultures. The zone of inhibition was recorded until no inhibition was observed. Biofilm prevention efficacy was investigated in 6 well plates. Bacterial cells (5×10. 5. CFU/mL in tryptic soy broth) were treated with ABLCBs. Media was removed and challenged with bacteria daily for 7 days. CFU counts were taken after 1, 2, 3 and 7 days. For biofilm killing, ABLCB were added to 3 day formed biofilms in 6 well plates. CFU counts were estimated at 1, 3 and 7 days with daily media exchange. Results. ABLCB demonstrated effective initial eluting concentrations depending on the strains. The NDM-1 strain of K. pneumoniae had lower sensitivity than other strains towards VAN & RIF and resistant towards VAN & GEN. E. faecalis was sensitive to both combinations. For repeat challenges, ABLCBs prevented colonisation and reduced biofilm formation, except for the NDM-1 strain which grew in the presence of VAN & GEN. Preformed biofilms were more difficult to reduce with antibiotics than in the prevention assay. Biofilm growth was observed at 1 week of contact with ABLCBs, despite negative cultures at earlier time points for K. pneumoniae and E. faecalis. However, there was a significant killing (2–3 logs, P<0.05) of biofilm bacteria with all antibiotic combinations compared to unloaded beads. Conclusions. This study provides evidence that local release of antibiotics from ABLCBs may be useful in the treatment of multidrug resistant strains of K. pneumoniae and E. faecalis (CRE and VRE) associated with PJIs. In-vitro results do not necessarily correlate to clinical results

Introduction: Screws placed in the fibula do not have a satisfactory purchase during internal fixation of an osteoporotic ankle fracture. Tibia-pro-fibula screws that extend from the fibula into the distal tibial metaphysis provide additional purchase. The purpose of this study is to investigate if purchase of these screws can be enhanced further by injecting calcium sulfate and calcium phosphate composite graft in the drill holes prior to insertion of the screws. Methods: Bone density was quantified using DEXA scan in paired cadaver legs. One leg from each pair was randomly selected for injection of composite graft into screw holes before insertion of the screws. Two screws were inserted through the fibula into the distal tibial metaphysis in each leg, at the level of the syndesmosis under fluoroscopy in a standardized fashion using a jig. The screws were pulled out using a materials testing machine. Stiffness, force, displacement, and energy required were recorded. Results: After testing 4 pairs of cadaver legs, a statistically significant difference was noted in displacement, failure load, and failure energy between augmented and non-augmented screws, with the augmented screws being considerably stronger. Of the two screws the distal, when compared to the proximal one, required more displacement, higher force and energy to fail whether augmented with composite graft or not. Conclusion: Screws augmented with composite graft provide significantly greater purchase in an osteoporotic distal tibial metaphysis than non-augmented screws. Clinical relevance: Use of composite graft to augment purchase of the screws inserted in the distal tibial metaphysis may enhance the stability of the internal fixation of an osteoporotic ankle fracture. This will enable early weight-bearing mobilization and return to function which is important in elderly patients

Introduction and Aims: Calcium sulfates and phosphates have become popular as bone graft substitutes, however, their in-vivo performance has not been well characterised. The purpose of this study was to evaluate trabecular bone response to four synthetic graft materials (CaSO4 and CaSO4 – HA/TCP composites) as compared to autograft in a canine defect model. Method: In this REB-approved RCT, bilateral humeral and femoral cylindrical defects were filled with one of four types of pellets with varying proportions of CaSO4 – HA/TCP, autograft bone, or left unfilled. After sacrifice at six or 12 weeks, defect sites were evaluated histologically for tissue and inflammatory response, area fractions of residual graft material, and bone ingrowth in the defects. Results: The area of the defect occupied by residual graft material in the group with the highest percentage of HA/TCP was greater than in other composite groups (p< 0.0006). At 12 weeks, this group contained more total mineralised material (graft material + bone) (p< 0.005). The extent of new bone formation was not different among the composite groups at either time-point, but all showed more bone formation than the empty defect. Both 100% CaSO4 and the 3 CaSO4 – HA/TCP formulations showed good bone formation. Conclusion: The group with the highest proportion of HA/TCP lasted longest, suggesting increased HA/TCP proportions reduce the rates of dissolution, without compromising bone formation in this model. Results suggest that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications

Core decompression is a common treatment for early stage osteonecrosis of the femoral head due to the simplicity of the procedure and the positive results of this intervention. A number of different core decompression methods exist: including methods backfilled by a bone graft material and those without filling. Due to the inherent desire that the core decompression defect regenerate healthy bone, reduce pain, and stave off the need for total hip arthroplasty for some period of time, this surgically created defect is an excellent application for the use of a bone graft substitute. Recently, an injectable calcium sulfate (CaSO. 4. )/calcium phosphate (CaPO. 4. ) composite graft has become available for use in the treatment of surgically created defects. The synthetic graft is an injectable composite of CaSO. 4. , tricalcium phosphate (TCP) granules, and brushite that hardens in situ. The triphasic resorption pattern exhibited by this material in vitro and in pre-clinical canine studies has indicated that the CaSO. 4. matrix resorbs at early time points to reveal a longer resorbing CaPO. 4. scaffold for bone onlay. In a canine proximal humerus model, the use of this material in a critical bone defect has demonstrated a regenerate with higher compressive strength at 13 week time points than defects treated with CaSO. 4. alone, defects treated with autograft, and normal untreated bone. By 26 weeks, the regenerated bone within the defect resembled normal bony architecture with similar mechanical properties. Early clinical series have indicated similar results to the canine studies. Reports of early clinical findings have included a 12 patient benign bone tumor series with 4–12 month follow up and a core decompression series of 38 Ficat stage I–III hips with 6–16 month follow up. Preliminary radiological results in the bone tumor series showed peripheral resorption of the injectable CaSO. 4. /CaPO. 4. composite with new bone formation along the resorbing edge. Clinically, patients in the bone cyst series have not experienced fractures or additional surgery and all patients have displayed full functional recovery. In the core decompression series, 32 of the 38 hips experienced pain relief and within the subset of 30 symptomatic hips, 24 had pain relief. These results, although preliminary, are promising outcomes. Collectively, the pre-clinical and preliminary clinical results indicate that the use of an injectable CaSO. 4. /CaPO. 4. composite could prove to be of benefit in core decompression of the femoral head. The staged resorption and dense bone formation evidenced in canine studies would be desirable in core decompression techniques where healthy bony ingrowth is the goal. Due to the straightforward compilation and use of this composite, the incorporation of this material as a backfill matrix into the core decompression procedure is technically simple. Although additional studies are certainly merited, these early clinical results are encouraging

The purpose of this study was to evaluate trabecular bone response to four different synthetic graft materials (CaSO. 4. and CaSO. 4. – HA/TCP composites) as compared to autograft in a canine defect model. The group with the highest HA/TCP proportion (and the lowest CaSO4 proportion) had the greatest amount of residual graft material and total mineralized material (p< 0.05). Increasing the proportion of HA/TCP reduces the rate of dissolution, and appears to have little effect on bone formation. This study suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications. Calcium sulfates and phosphates have become popular clinically for use as bone graft substitutes, however, their in-vivo performance has not been well characterized. The purpose of this study was to evaluate trabecular bone response to four synthetic graft materials (CaSO. 4. and CaSO. 4. – HA/TCP composites) as compared to autograft in a canine defect model. Both 100% CaSO. 4. and the 3 CaSO. 4. – HA/TCP formulations showed good bone formation. The group with the highest proportion of HA/TCP lasted longer than the other formulations, suggesting increased HA/TCP proportions reduce the rates of dissolution, without compromising bone formation in the current model. Results suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications. In this REB-approved RCT, bilateral humeral and femoral cylindrical defects were filled with one of four types of pellets with varying proportions of CaSO. 4. – HA/TCP, autograft bone, or left unfilled. After sacrifice at six or twelve weeks, defect sites were evaluated histologically for tissue and inflammatory response, area fractions of residual graft material, and bone ingrowth in the defects. The area of the defect occupied by residual graft material in the group with the highest percentage of HA/TCP was greater than in other composite groups (p< 0.0006). At twelve weeks, this group contained more total mineralized material (graft material + bone) (p< 0.005). The extent of new bone formation was not different among the composite groups at either time-point, but all showed more bone formation than the empty defect. Funding: This study was funded by a research grant from Stryker Howmedica, Matwah, NJ

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

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).

Purpose: Bone grafting of subchondral voids during ORIF of tibial plateau fractures is commonly performed. The efficacy of various graft materials to resist post-operative articular displacement and stimulate bone regeneration in the grafted zone, remains largely unstudied. Studies in animals with a new composite material have shown that this composite material leads to greater bone formation and stronger bone versus autograft at 13 and 26 weeks. This study was designed to determine whether this material helps resist articular fragment displacement and leads to stronger bone regeneration and better functional outcome in the treatment of tibial plateau fractures.

Methods: Thirty four patients with unilateral tibial plateau fractures (OTA 41A-B), were enrolled in a prospective multicenter single cohort study. The treatment protocol included ORIF and defect augmentation with a composite bone graft substitute (PRODENSE®, Wright Medical Technology). Reduction and bone formation was evaluated and followed with both plain radiographs and CT scans obtained immediately postop and at 12 and 24 weeks. Functional outcome was assessed using the SMFA scores. CT analysis was performed by an independent musculoskeletal radiologist who quantified maintenance of reduction of the articular surface and bone density within the grafted area.

Results: Eighteen of the 34 enrolled patients were eligible for follow-up at 24 weeks (sixteen were not yet eligible for the 24 week time point). Mean change in articular reduction was 0.75mm, Density measures in the region of the initial subchondral void decreased from a mean of 1400 Hounsfield units at baseline (immediately post-op) to 600 at 24 weeks, suggesting bone regeneration and normal remodeling. Short form Musculoskeletal Function Assessment activity scores improved from 55.15 (SD=42.8) at baseline to 20.92 (SD=18.09) at 24 weeks. Complications include 1 DVT, 3 infections and 1 cellulitis, all of which resolved. There was an additional infection that required revision of the ORIF.

Conclusions and Significance: Serial CT evaluations revealed maintenance of post-operative reduction with displacement of less than 1mm. Bone density, in the region of the grafted area was near normal and confirms that the composite graft material promotes strong bone regeneration. Functional outcomes improved with time from surgery and approached that of uninjured cohorts.

The purpose of this study was to evaluate trabecular bone response, at fifty-two week follow-up, to four different synthetic graft materials (CaSO4 and CaSO4 – HA/TCP composites) as compared to autograft in a canine defect model. The group with the highest HA/ TCP proportion had the greatest amount of residual graft material and total mineralized material. Increasing the proportion of HA/TCP reduces the rate of dissolution, and appears to have little effect on bone formation at long term follow-up. This study further suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications.

The purpose of this study was to evaluate trabecular bone response to four synthetic graft materials (CaSO4 and CaSO4 – HA/TCP composites) as compared to autograft in a canine defect model, at long term follow-up.

Both 85% CaSO4 – 15% HA/TCP and 65% CaSO4 – 15% HA/TCP showed bone formation similar to autograft. The group with the highest proportion of HA/TCP lasted longer than the other formulations. The results suggest that increased HA/TCP proportions reduce the rates of dissolution, without compromising bone formation in the current model.

Results suggests that a range of composites could be created to match the spectrum of resorption rates demanded by clinical applications.

In this REB-approved RCT, bilateral humeral and femoral cylindrical defects were filled with one of four types of pellets with varying proportions of CaSO4 – HA/TCP, autograft bone, or left unfilled. After sacrifice at six, twelve, twenty-six or fifty-two weeks, defect sites were evaluated histologically for tissue and inflammatory response, area fractions of residual graft material, and bone ingrowth in the defects.

The area of the defect occupied by residual graft material in the group with the highest percentage of HA/TCP was greater than in other composite groups (p< 0.0001). This group contained the greatest amount of total mineralized material (graft material + bone) (p< 0.03. The extent of new bone formation increased from twelve to twenty-six weeks (p< 0.0001). Both 85% CaSO4 – 15% HA/TCP and 65% CaSO4 – 15% HA/TCP showed bone formation similar to autograft.

Funding: Research grant from Stryker Howmedica, Matwah, NJ.

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. Megaprosthesis have become a standard option in limb preserving surgery after bone resection in musculoskeletal tumors. Recently they have also been used in complex revision arthroplasty in cases with massive bone loss. The aim of this study was to analyze the incidence of periprosthetic joint infection (PJI) both in primary oncology cases and aseptic revision cases and analyze which are the significant risk factors for PJI with a special interest on the use of prophylactic antibiotic loaded calcium sulfate beads. Method. All patients undergoing surgery with the use of megaprosthesis in our institution between January/2012 and December/2022 were retrospectively reviewed. Data was collected from electronic medical records. We identified 108 procedures involving megaprosthesis in 90 patients with an average follow-up of 37 months. Indications were 79 primary musculoskeletal tumors and 29 aseptic complex revision arthroplasty. Results. Table 1 shows relevant clinical information. No significant risk factor was found either in uni or multivariate analysis. PJI rate was 15% (12/79) for primary musculoskeletal surgery and 31% (9/29) for complex revision surgery. The use of antibiotic loaded calcium sulfate beads did not show an advantage – 22% (9/41) with vs. 18% (12/67) without. Conclusions. In this relatively small series it was not possible to show a significal association between PJI and certain known risk factors such as gender, ASA score, site of surgery (knee) and revision surgery. The use of antibiotic loaded calcium sulfate beads as prophylaxis was not beneficial in reducing PJI rates in our cohort. We acknowledge the limitations of our study: a small sample group, in a single institution with heterogeneity in terms of diagnosis and surgical site. We recognize the need for a multicentric study with a larger cohort to validate these findings. For any tables or figures, please contact the authors directly