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

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

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

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

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

Introduction. Since the expanded war in Ukraine in 2022, explosives, mines, debris, blast waves, and other factors have predominantly caused injuries during artillery or rocket attacks. These injuries, such as those from shelling shrapnel, involve high-energy penetrating agents, resulting in extensive necrosis and notable characteristics like soft tissue defects and multiple fragmentary fractures with bone tissue defects and a high rate of infection complications caused by multi resistant gram-negative (MRGN) pathogens. Material and Methods. We conducted a prospective study at our center between March 2022 and December 2023. Out of the 56 patients from Ukraine, 21 met the inclusion criteria who had severe war injuries were included in the study. Each of these patients presented with multiple injuries to both bones and soft tissues, having initially undergone treatment in Ukraine involving multiple surgeries. The diagnosis of infection was established based on the EBJIS criteria. Prior to our treatment patients had undergone multiple revision surgeries, including debridement, biopsies, implant and fixator replacement. Additionally, soft tissue management required previously VAC therapy and flap reconstruction for successful treatment. Results. All 21 infections manifested as bone infections (11; 52%), followed by implant-associated infections (5; 24%), soft tissue infections (4; 19%), and septic arthritis (1; 5%). In all patients, the infection was polymicrobial, caused by 3- and 4-MRGN pathogens, as Klebsiella pneumonia 4MRGN, Proteus mirabilis 4MRGN, Enterobacter cloacae 4MRGN etc. Upon admission, all patients carried a diagnosis and exhibited signs indicative of chronic infection. 19 (90.5%) patients required complex antibiotic regimens combined with multiple wound revisions and debridements, changes of fixators and combination of systemic and local antibiotic therapy. In 6 patients (28%) high dosages of local antibiotics such as gentamycin, vancomycin and meropenem were incorporated into a carrier of bio-absorbable calcium sulfate, calcium sulfate/hydroxyapatite which were introduced into the hip joint, femoral canal or bone defect for dead space management during the surgery. When local antibiotics were administered at intervals, the microbiology results at implantation showed negative results. 2 (9%) patients had new infections (different site, different pathogens), 1 (4.8%) is still under the treatment. In 17 (81%) patients infection complications were treated successfully with no recurrence of infection. Conclusion. War injuries result in complex bone and soft-tissue infections caused by 3-, 4-MRGN pathogens. Addressing this challenge necessitates multidisciplinary approach with multiple, thorough surgical debridements, effective local, and systemic antimicrobial therapy. As for the outlook we can see potential in local antibiotic carriers

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

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

Purpose. To analyze the effectiveness of a vancomycin impregnated calcium sulfate cement bead insertion after debridement (of) an acute-immediate stage infected hip arthroplasty. Materials and Methods. Between 2002 and 2008, 13 patients with documented acute-immediate stage infection of hip arthroplasty were reviewed and followed for at least two years postoperatively(average 4.3 years). The preoperative and postoperative clinical and radiologic findings and blood laboratory work were checked. All cases were performed through retention of the implant and massive debridement and saline irrigation. After that a vancomycin impregnated calcium sulfate cement beads was inserted. Results. After the first operation, the average interval for second operation was 27.7 days (17–37). At the second operation, the erythrocyte sediment rate and C-reactive protein were 150.97 mm/hr (34.6 ∼339.7 mm/hr) and 76.4 mg/L (41∼132 mg/L) respectively. Infectious organism were cultured and isolated. There were 5 cases of Methicillin resistant staphylococcus aureus (MRSA). In addition, results of an antibiotics sensitivity test were 8 cases of Vancomycin, and 5 cases of 3rd generation Cephalosporin. Radiologic results showed 10 cases with stable fixation on last follow-up (femoral stem) and 1 case of hip joint space narrowing, acetabular erosion. Conclusion. Vancomycin impregnated, calcium sulfate, cement bead insertion for an acute immediate infection of hip arthroplasty proved to be a useful method

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

Introduction. Cerament, a bioresorbable hydroxyapatite and calcium sulfate cement, is known to be used as a bone-graft substitute in traumatic bone defect cases. However, its use in open fractures has not previously been studied. Materials and Methods. Retrospective, single-centre review of cases between November 2016 and February 2021. Open fractures were categorised according to the Orthopaedic Trauma Society classification (OTS). Cases were assessed for union, time to union, and associated post-operative complications. Results. Twenty-four patients were identified. Fifteen cases were classified as OTS simple open fractures, and nine cases were complex open fractures requiring soft tissue reconstruction. Four cases were lost to follow-up. Four cases had limited follow-up beyond 6 months but showed evidence of progressive radiographic union. Of the remaining 16 cases, eight cases (50%) went on to union with a mean time to union of 6.7 months (5 to 12 months). Persistent non-union remained in six cases (38%). Two cases required return to theatre due to an infected skin graft and wound dehiscence respectively. One case had the complication of persistent weeping of Cerament from the wound. This self-resolved within two weeks. Limitations of this case series include the lack of complete follow-up in eight patients (33%) and the lack of patient reported outcome measures. Conclusions. Cerament can be a useful adjunct in managing open fractures. However, it should be noted there is a high rate of non-union which may be reflective of the significant morbidity associated with open fractures with structural bone defects

Aim. The use of bone substitutes such as calcium sulfate (CaSO4) and hydroxyapatite with local antibiotics are crucial in the treatment of osteomyelitis. They allow the treatment of the dead space and locally provide large concentrations of antibiotics. However, it is unknown whether use of local vancomycin may elute and influence on vancomycin plasma levels. The aim of this study is to assess whether the addition of vancomycin to CaSO4 with hydroxyapatite may increase vancomycin plasma concentrations in in patients with osteomyelitis and therefore alter dosage adjustments. Method. The present study investigates the vancomycin plasma concentrations at 72–94 h post-surgery after the application of local vancomycin within CaSO4 (660mg vancomycin/10cc) and hydroxyapatite bone substitute in patients treated with empiric intravenous vancomycin and surgically treated for osteomyelitis. Vancomycin plasma concentrations were analyzed in twelve patients with osteomyelitis surgically treated with local release of vancomycin by CaSO4 and hydroxyapatite and undergoing therapeutic drug monitoring (TDM) of their vancomycin plasma concentrations as it is routinely done in our hospital. From 2019 to 2022, demographic data, microbiology, type of osteomyelitis, amount of local vancomycin applied, alteration of renal function, and vancomycin levels were retrospectively analyzed. Results. Twelve patients were included: 9(75%) were men. Median (range) demographic and clinical data: age: 51(26–67) years; body mass index: 27.7(18–46.4) kg/m2;baseline serum creatinine: 0.85 (0.7–1.24)mg/dl and 5(41.7%) with and glomerular filtration rate < 90ml/min(CPD-EPI, ml/min). Most frequently isolated microorganisms were Staphylococci (58%). Seven (54%) patients were classified as Cierny-Mader Osteomyelitis type III, 3(23%) as type IV and 2(23%) as type I. Treatment data: initial dose of vancomycin: 1g/8h in 9(75.0%) and 1g/12h in 3(25%) patients, total daily dose/body weight: 35.3(15.9–46.2) mg/kg. Pharmacokinetic data:days of iv vancomycin treatment until first TDM measurement: 3(3–4) days; minimum and maximum vancomycin plasma concentrations: 9.4(3–17.3) mg/L and 19.6(11.3–33.4) mg/L, respectively; patients with therapeutic concentrations: 6(50%); infratherapeutic: 4(33.3%) and supratherapeutic/potentially toxic: 2(16.7%). These 2 patients were young, had a baseline conserved renal function and were receiving the higher dose of 1g/8h. Conclusions. Vancomycin incorporated into the bone substitute appears not to increase blood concentrations of the glycopeptide in patients with osteomyelitis treated surgically and with intravenous vancomycin. However, 2 of the 12 patients presented supratherapeutic and potentially nephrotoxic vancomycin concentrations in the first TDM measurement, even though they were young and without renal impairment and needed and unexpected dose reduction. These results suggest the need to confirm the safety of local vancomycin in further larger clinical studies

Aim. Dissolvable antibiotic-loaded calcium sulphate beads have been utilized for management of periprosthetic joint infection (PJI) and for aseptic revision arthroplasty. However, wound drainage and toxic reactive synovitis have been substantial problems in prior studies. Currently a commercially pure, physiologic product has been introduced that may reduce complications associated with this treatment modality. We aim to answer the question: does a commercially pure, physiologic version of antibiotic-loaded calcium sulfate beads reduce wound drainage and provide efficacious treatment for PJI and aseptic revision arthroplasty?. Method. Starting January 2010, 756 consecutive procedures were performed utilizing a set protocol of Vancomycin and Tobramycin antibiotics in commercially pure dissolvable antibiotic beads. There were 8 designated study groups:. Aseptic Revision TKA. N = 216. Aseptic Revision THA. N = 185. DECRA. *. TKA. N = 44. DECRA. *. THA. N = 16. 1. st. Stage Resection TKA. N = 103. 1. st. Stage Resection THA. N = 62. Reimplant TKA. N = 81. Reimplant THA. N = 49. *. DECRA = Debridement, modular Exchange, Component Retention, iv Antibiotics for acute PJI. Results. Wound drainage in the entire series was 4.2%. Wound drainage was generally seen in cases using higher bead volumes (≥30cc). The rate of heterotopic ossification was 1.6%. With bead volumes of ≥30cc, we did notice transient hypercalcemia in 12% of the study group (14% hips, 10% knees). The overall rate of infection failure was 2.5%. In the DECRA groups, reinfection failure rate was encouraging, measuring 9.1% in knees and 6.3% in hips. The non-DECRA group with the highest infection rate was Reimplant TKA (6.2%). Conclusions. We utilized a large series of commercially pure dissolvable antibiotic-loaded beads in a wide variety of clinical scenarios in patients with substantial comorbidities. Our rate of wound drainage, compared to prior studies utilizing gypsum products, was reasonably good. Additionally, our infection failure rates were encouraging. Over-stuffing knee joints with too many beads, in our clinical review, does affect wound drainage rates. By removing impurities from calcium sulfate, we do not see the substantial toxic synovial reaction compared to the traditional gypsum-washed products. We feel that commercially pure, physiologic antibiotic-loaded dissolvable beads are an acceptable delivery tool for local antibiotic delivery in aseptic and septic revision joint arthroplasty of the hip and knee. In our opinion, further study is warranted. We advocate future randomized studies to examine the potential of improving outcomes of PJI and aseptic revision arthroplasty