Purpose. The aim of this study was to assess the clinical and radiological result of the usage of chip bone graft in non-contained type bone defect in primary or revision total knee arthroplasty patients. Subjects and Methods. We investigated 32 patients who had underwent primary or revision total knee arthroplasty from March, 2014 to February, 2017 in our hospital, who had non-contained type of defect. The mean age was 73.1 years. 5 of them were males, while 27 of them were females. 7 of them were primary total knee arthroplasty patients, while 25 of them were revision patients. 8 of them had chip bone graft used both in the femur and tibia. 9 of them had chip bone graft used only in the tibia. The other 15 had chip bone graft used only in the femur. Wire-mesh was used in the 9 patients who had chip bone graft used only in the medial side of the tibia. We used KOOS (Knee injury and osteoarthritis outcome score), HSS (Hospital for Special Surgery knee service rating system) and WOMAC scores to assess the clinical result, before the surgery and at the last follow-up. In addition, we had follow-up x-rays and 3D CT done for the patients to check the mean bone union period. In addition, overall radiologic imaging studies were used for complications such as loosening, osteolysis and lesions with radiolucency. Result. The Mean follow-up period was 2.7 years (range; 2.1 to 5). The Mean preoperative KOOS was 102.8 (range; 47 to 132), while it became 31.8 postoperatively (range; 20 to 45). The mean HSS was 13.1 (range; 6 to 35), while it became 35.9 postoperatively (range; 24 to 64). The mean WOMAC was 82.9 (range; 62 to 92), while it became 22.5 postoperatively (range; 13 to 30). According to follow-up x-ray and CT, the mean bone union period was 10.6 months (range: 10 to 13). In follow-up 3D CT of all cases, we could check cortical healing and new bone formation, seen as medium to high-attenuating conglomerate. The graft-host junction showed trabecular ingrowth, while the medullary canal showed fibrous ingrowth. Radiologically, there was no complication such as loosening, osteolysis, migration and radiolucent lines around the stems or cement mantles. In addition, there was no complication such as infection. Conclusion. Chip bone graft is not a commonly used method for bone defect in total knee arthroplasty. According to the result of the usage of chip bone graft in primary or revision total knee arthroplasty with non-contained type of bone defect, it showed favorable result for the subject patients. Therefore, we can consider it as one of the effective methods to manage non-contained bone defect in knee arthroplasty. Keywords. Revision TKA, chip bone graft, wire-mesh, non-contained bone defect. For any figures or tables, please contact authors directly

Introduction. Tunnelwidening in failed anterior cruciate ligament reconstruction (ACLR) can result in the staged revision procedures with a need for bone transplantation prior to revision reconstruction. Limited knowledge exist regarding to quality of different transplantation methods. The present study used CT-scanning to evaluate tunnel bone density after allogenic bone chips and bone cylinder transplantation. We hypothesized that bone chips transplantation resulted in higher bone density than bone cylinder transplantation due to possible voids between individual cylinders in the tunnels. Methods. The records of 24 patients operated for 1st stage revision ACLR from April 2003 to march 2010 were included in the study. twelve patients had their tunnels transplanted with bone chips and twelve patients with bone cylinders from allogenic femoral heads. Bone chips were created by fine bone milling and cylinders were extracted by 7–8 mm core drilling. Bone density 3–4 months after transplantation were evaluated by CT scanning reconstruction slides with 5 mm intervals throughout the tunnel length using histomorphometry. Results. There were 15 females and 9 males with an average age of 32 yrs. Using bone chips the bone density in the tibial tunnels was 55% and the femoral tunnels the bone density was 68% Using bone cylinders bone density was 60% in the tibial tunnels and 53% in the femoral tunnels. The femoral bone density in the bone chip group was significantly higher than the bone cylinders (p < 0.05). Conclusion. Transplantation with bone chips results in superior bone quality in the femoral tunnels where as no difference where demonstrated in the tibial tunnels

Introduction: The nonunion rate is higher and loss of reduction is common after reduction and fusion for the higher grades of spondylolisthesis. This is due to fusion bone base deficiency and lack of anterior column support, and can be addressed by supplementing the posterolateral fusion with a posterior lumbar interbody fusion (PLIF). Materials: All patients had a single disc level degenerative or spondylolytic slip exceeding 25%. Laminectomy and instrumented reduction (VSP or TSRH) was performed. 86 patients underwent posterolateral fusion and 82 underwent the same procedure plus a PLIF (done by tightly impacting bone chips into the disc cavity after a very aggressive discectomy). No fusion cages were used. Results: Presented as No-PLIF vs. PLIF. Age: 56 vs. 52 years. Male/Female: 14:72 vs. 15:67. Cases with pars fx: 44% vs. 56%. Level of slip (L3-4, L4-5, L5-S1): 9, 59, 18 vs. 4, 60, 18. Iatrogenic neurological injury: none vs. none. Deep infection: 1 vs. none. Nonunion: 9.3% vs. 2.4%. Broken screws: 6 vs. 2. Degree of slip (pre-op to post-op to 2 years): 34% to 11% to 20% vs. 38% to 4% to 8%. Patients that lost reduction: 67% vs. 18%. Disc height gained at 2 years: −0.2 mm vs. 2.3 mm. Subjective back pain score: 3.5 vs. 2.0. Greenough LBOS score: 54 vs. 62. Patients very satisfied: 43% vs. 60%. Cases with adjacent level slip: 4 vs. 4. Discussion: Spondylolisthesis is commonly treated with a spinal fusion. The goal of surgery is to eliminate motion between the unstable segments, and mechanically it is preferable that the vertebrae fuse in as near anatomic position as possible. It has been shown that the fusion rate decreases with higher degrees of slip, with the spondylolytic types, and with severely degenerated discs. Pedicle screw instrumentation can increase the fusion rate. Reduction of the slip can often be achieved, but it is common to lose the reduction over the course of 1–2 years if only posterolateral fusion is done. Adding an interbody fusion cage can help restore the disc height and widen the intervertebral foramen, but increases complexity, cost, and may actually decrease bone contact area and compression forces. We have found that in grade II and worse slips, pedicle screw fixation alone is not strong enough to maintain reduction of either vertebral alignment or disc height. Adding a chip PLIF appears safe and effective in increasing the union rate and the disc height, and in maintaining reduction in grade II spondylolisthesis. Clinical results are better, the infection rate is not higher. In our hands, there have been no neurological injuries. This study also raises questions about the role and need for interbody fusion cages

We present a retrospective study of comparision between two types of aritifical boen graft substitues. There is an overwhelming marketting drive on part of companies to sell alternative bone grafts/BMP. We in this study compae two such producsts and their cost effectiveness. This is an interventional, retrospective, non consecutive, non randamised case series study of 27 patients. Type I bone graft is Mini MIIG which is surgical grade calciun sulphate which is osteoconductive. Type II bone graft is Allomatrix which conatins bone marrow aspirate, bone morphogenic protein, concellous bone chips and surgical grade calciun sulphate which is osteogenic, osteoinductive and osteoconductive. In this study 14 cases were treated with Mini MIIG and 18 with Allomatrix. There were 24 primary fractures with bone defect, 2 non union and 1 delayed union. Complete bony union were seen in all 27 patients. Average time to heal since bone grafting is 3 months. Complications are extrubent callus formation, bone formatiom in soft tissue, but no patient required secondary procedure to trim the bone. Cost for Allomatrix is £ 356.00 and Mini MIIG is £348.00. Use of such artificial bone grafting avoids the complication of autografting which includes bone graft side morbidity like pain, bleeding and neurvascular damage. For fresh fractures useage of such artificial bone grafts doesnt shorten the healing time, doesnt prevent collapse at fracture site and it is not cost effective. For non union and delyaed unions it avoids the cost for artifical bone grafting. But autograft also incurs the cost of removing, theatre timing. human resources cost and hospital inpatient costs. There is no difference between one type of bone graft over the other and for fresh fracture both of them has no advantage over using no bone grafts. Our study concludes artifical bone graft is of no advantage for fresh fractures and for non union and delayed unions it is too small a number to come to any conclusion

A modular tibial insert exchange is a seemingly attractive benign and simple surgical alternative when compared to full knee revision. Unfortunately, the results have been less than satisfactory with modular insert exchange for polyethylene wear and knee instability. Babis et al reported the results of 56 isolated insert exchanges performed for wear or instability. The re-revision rate was 25% at a mean follow-up of 3-years and the cumulative survival rate was only 63.5% at 5.5 years. In another study, 27% (6/22) insert exchanges for wear required re-revision within 5 years. Bert et al reported scoring and damage in 89% of 55 retained components considered candidates for isolated insert exchange. Such damage could account for accelerated wear of a new insert.

These studies are misleading. The new insert must be polyethylene not prone to oxidation and accelerated wear. In a recent study of 177 revisions for wear and osteolysis, the survivorship of insert exchange using non-irradiated poly was 100%. Insert exchange does not correct the problem of a poor tibial locking mechanism. Whiteside and Katerberg reported 3 failures in 49 insert exchanges, fabrication of the tibial locking mechanism was used to address this problem. With revision for instability, insert exchange must provide full stability in both flexion and extension.

Tibial insert exchange must correct the underlying cause of failure that led to the revision surgery. Full knee revision is a complex procedure that brings with it increased risks of perioperative complications such as infection and should be reserved only for cases that will not do well with simple insert exchange.

From 1985 through 1997, 56 isolated tibial insert exchange revisions were performed at our institution. Fifty-five patients with wear or instability were included. Those with loosening of any of the components, history of infection, severe knee stiffness or problems with the extensor mechanism were excluded. There were 29 males (1 bilateral) and 26 female patients with a mean age of 66 years (range 35 to 83 years) at the time of revision surgery. Twenty-seven inserts were exchanged based on ligamentous instability, 24 because of insert wear or breakage including two cases of polyethylene dislodgment from the tibial base-plate and 5 for other reasons. Twelve knees had one to three prior revisions. Surveillance from index arthroplasty averaged 8.3 years (range 1.6 to 16.2 years) and since revision 4.6 years (range 2 to 14 years).

Knee Society and Function Scores improved from 56 and 50.9 prior to revision to 76 and 59 at final surveillance respectively. Fourteen (25%) of the 56 knees subsequently required re-revision after a mean of only three years (0.5–6.8) from tibial insert exchange. The cumulative survival at 5.5 years was 63.5% (95%CI=+/−14.4, n=19). Of the 27 patients with pre-operative instability, eight were revised and another four were considered as failures due to severe pain. Of the 24 failed inserts, five were re-revised, one was amputated as a result of chronic ankle osteomyelitis concomitant to a chronically painful arthroplasty, and another two inserts failed due to severe pain.

Isolated tibial insert exchange led to a surprisingly high early failure rate. Tibial insert exchange should therefore be undertaken with caution as an isolated method of total knee revision surgery even in those circumstances for which the modular insert was designed and felt to be of greatest value.

Aim. Local antibiotics released through a carrier is a commonly used technique to prevent infection in orthopaedic procedures. An interesting carrier in aseptic bone reconstructive surgery are bone chips impregnated with AB solution. Systemically administered Cefazolin (CFZ) is used for surgical site infection prophylaxis however in vitro study showed that fresh frozen and processed bone chips impregnated with CFZ solution completely release the CFZ within a few hours. On the other hand irradiated freeze-dried bone chips, treated with supercritical CO2 (scCO2) have been shown to be an efficient carrier for the antibiotics vancomycine or tobramycine. With this pilot study we wanted to investigate if CFZ solution impregnation of bone chips treated with scCO2 shows a more favorable release pattern of CFZ. Method. The bone chips were prepared using the standard scCO2 protocol and were impregnated with 100 mg/ml cefazolin at different timepoints during the process: before freeze drying (BC type A), after freeze drying (BC type B) and after gamma-irradiation. 0.5g of the impregnated bone grafts were incubated with 5ml of fetal calf serum (FCS) at 37°C. At 2, 4, 6, 8 and 24h of incubation 200µl of eluate was taken for analysis. After 24h the remaining FCS was removed, bone grafts were washed and new FCS (5ml) was added. Consecutive eluate samples were taken at 48, 72 and 96h of incubation. The concentration of CFZ in the eluates was measured with the validated UPLC-DAD method. Analysis was performed in triplicate. Results. The mean concentration of CFZ in the eluate obtained from BC type A incubated for 2h was higher compared to BC type B, respectively 581 mg/l and 297 mg/l. However, the elution profile is the same for both types: the CFZ concentration in the eluates drops within the first 24h from 581 mg/l to 365 mg/l (37%) for BC type A and from 297 mg/l to 132 mg/l (56%) for BC type B. After 24h no further significant CFZ release is seen. Impregnation of the bone chips before or after gamma irradiation did not affect this elution profile. Conclusions. Bone chips treated with scCO2 show a comparable elution pattern compared to non-scCO2 treated bone chips. AB release depends on the properties of the AB, making it impossible to copy the same impregnation protocol for different antibiotics. The stability of CFZ in solution at 37°C and its release are a major concern when establishing an impregnation protocol with CFZ

Aims. Osteochondral lesions of the talus (OLT) are a common cause of disability and chronic ankle pain. Many operative treatment strategies have been introduced; however, they have their own disadvantages. Recently lesion repair using autologous cartilage chip has emerged therefore we investigated the efficacy of particulated autologous cartilage transplantation (PACT) in OLT. Methods. We retrospectively analyzed 32 consecutive symptomatic patients with OLT who underwent PACT with minimum one-year follow-up. Standard preoperative radiography and MRI were performed for all patients. Follow-up second-look arthroscopy or MRI was performed with patient consent approximately one-year postoperatively. Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) score and International Cartilage Repair Society (ICRS) grades were used to evaluate the quality of the regenerated cartilage. Clinical outcomes were assessed using the pain visual analogue scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Scale (FAOS). Results. All patients had ICRS grade IV cartilage lesions, except for one (ICRS grade III). The paired MOCART scores significantly improved from 42.5 (SD 1.53) to 63.5 (SD 22.60) (p = 0.025) in ten patients. Seven patients agreed to undergo second-look arthroscopy; 5 patients had grade I (normal) ICRS scores and two patients had grade II (nearly normal) ICRS scores. VAS, FFI, and all subscales of FAOS were significantly improved postoperatively (p ≤ 0.003). Conclusion. PACT significantly improved the clinical, radiological, and morphological outcomes of OLT. We consider this to be a safe and effective surgical method based on the short-term clinical results of this study. Cite this article: Bone Jt Open 2023;4(12):942–947

Aim. Allograft bone chips used in complex bone reconstruction procedures are associated with an increased infection risk. The perioperative use of systemic cefazolin is standard to prevent infection, but is less effective in the presence of avascular bone grafts. Bone chips have been described as a carrier for local delivery of antibiotics, but impregnation with cefazolin in a prophylactic setting has not been described. We aimed to obtain a prolonged cefazolin release from bone chips to maximize the prophylactic effect. Method. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were incubated for 20 min- 4h under atmospheric pressure or under vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results. Without hydrogel, cefazolin release was limited to 4 hours. When vacuum was applied during impregnation, elution of cefazolin exceeding the MIC (minimal inhibitory concentration) from decellularized lyophilized bone chips was obtained for 36 hours. Use of a collagen hydrogel and vacuum treatment resulted in a high concentration at 24 hours, but did not support prolonged release for any of the three types of tested bone chips. In contrast, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 μg/ml, declining to the MIC at 72 hours, while no longer measurable after 92 hours. Such elution profile is desirable, since high initial levels are important to maximize antibacterial action whereas the complete wash out prevents antibiotic resistance. By increasing the cefazolin concentration during impregnation, elution above the MIC could be obtained for 120 hours. Impregnated bone chips stored at −20° C for 3 months performed similarly to freshly impregnated bone chips. Conclusions. Bone chips processed with the described hydrogel-based impregnation protocol allows tunable delivery of cefazolin for a local prophylactic effect

Vertebral metastases are the most common type of malignant lesions of the spine. Although this tumour is still considered incurable and standard treatments are mainly palliative, the standard approach consists in surgical resection, which results in the formation of bone gaps. Hence, scaffolds, cements and/or implants are needed to fill the bone lacunae. Here, we propose a novel approach to address spinal metastases recurrence, based on the use of anti-tumour metallic-based nanostructured coatings. Moreover, for the first time, a gradient microfluidic approach is proposed for the screening of nanostructured coatings having anti-tumoral effect, to determine the optimal concentration of the metallic compound that permits selective toxicity towards tumoral cells. Coatings are based on Zinc as anti-tumour agent, which had been never explored before for treatment of bone metastases. The customized gradient generating microfluidic chip was designed by Autodesk Inventor and fabricated from a microstructured mould by using replica moulding technique. Microstructured mould were obtained by micro-milling technique. The chip is composed of a system of microfluidic channels generating a gradient of 6 concentrations of drug and a compartment with multiple arrays of cell culture chambers, one for each drug concentration. The device is suitable for dynamic cultures and in-chip biological assays. The formation of a gradient was validated using a methylene blue solution and the cell loading was successful. Preliminary biological data on 3D dynamic cultures of stromal cells (bone-marrow mesenchymal stem cells) and breast carcinoma cells (MDA-MB-231) were performed in a commercial microfluidic device. Results showed that Zn eluates had a selective cytotoxic effect for tumoral cells. Indeed, cell migration and cell replication of treated tumoral cells was inhibited. Moreover, the three-dimensionality of the model strongly affected the efficacy of Zn eluates, as 2D preliminary experiments showed a high cytotoxic effect of Zn also for stromal cells, thus confirming that traditional screening tests on 2D cultured cells usually lead to an overestimation of drug efficacy and toxicity. Based on preliminary data, the customized platform could be considered a major advancement in cancer drug screenings as it also allows the rapid and efficient screening of biomaterials having antitumor effect

To prevent infections after orthopedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics. Bone allografts impregnated with antibiotics may therefore provide the necessary local antibiotic levels for prophylaxis. To be efficient, a prolonged release from these bonechips is required. In contrast to vancomycin, for which prolonged release has clearly been proven effective from Osteomycin®, a commercially available impregnated bone allograft, no prolonged release bone chip preparations have been described so far for cefazolin. We developed a protocol to bind cefazolin in the porous structure of bone chips by means of a hydrogel composed of proteins naturally present in the human body. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analyzed by Ultra Performance Liquid Chromatography – Diode Array Detection. Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile is desirable, since high initial levels are important to maximize anti-bacterial action whereas low levels of antibiotic for a limited time may stimulate osteogenesis. It is important that antibiotic release is ending after a few days as prolonged low levels of antibiotics are not clinically helpful and may lead to antibiotic resistance. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips

Aim. To prevent infections after orthopaedic surgery, intravenous antibiotics are administered perioperatively. Cefazolin is widely used as the prophylactic antibiotic of choice. Systemic antibiotic therapy may however be less effective in longstanding surgery where bone allografts are used. Bone chips have been shown to be an effective carrier for certain types of antibiotics and may provide the necessary local antibiotic levels for prophylaxis. To be efficient a prolonged release is required. In contrast to vancomycin with proven efficient prolonged release from Osteomycin, this has not been described for cefazolin. We developed a protocol to bind cefazolin to bone chips by means of a hydrogel composed of proteins naturally present in the human body. Method. Three types of bone chips were evaluated: fresh frozen, decellularized frozen and decellularized lyophilized. Bone chips were incubated with 20 mg/ml cefazolin or treated with liquid hydrogel containing either 1 mg/ml fibrin or 1 mg/ml collagen and 20 mg/ml cefazolin. The cefazolin hydrogel was distributed in the porous structure by short vacuum treatment. Bone chips with cefazolin but without hydrogel were either incubated for 20 min- 4h or also treated with vacuum. Cefazolin elution of bone chips was carried out in fetal bovine serum and analysed by Ultra Performance Liquid Chromatography – Diode Array Detection. Results. Soaking of bone chips without hydrogel resulted in a quick release of cefazolin, which was limited to 4 hours. When vacuum was applied elution of >1 µg/ml cefazolin was measured for up to 36 hours. Combination with collagen hydrogel resulted in a higher cefazolin concentration released at 24 hours (3.9 vs 0.3 µg/ml), but not in a prolonged release. However, combination of decellularized frozen bone chips with fibrin hydrogel resulted in an initial release of 533 µg/ml followed by a gradual decline reaching the minimal inhibitory concentration for S. aureus at 72 hours (1.7 µg/ml), while not measurable anymore after 92 hours. Conclusions. Processed bone chips with hydrogel-cefazolin showed a markedly prolonged cefazolin release. When combined with a fibrin hydrogel, high initial peak levels of cefazolin were obtained, followed by a decreasing release over the following three days. This elution profile seems desirable, with high initial levels to maximize anti-bacterial action and low levels for a limited time to stimulate osteogenesis. Further preclinical studies are warranted to show effectiveness of hydrogel-cefazolin impregnated bone chips

The complex structural arrangement of bone gives rise to anisotropic, rate-dependent failure behaviour, which varies significantly depending on tissue composition and architecture. This presents significant challenges in the development of orthopaedic surgical cutting instruments, which are required to generate sufficient forces to penetrate bone tissue, while minimizing the risk of thermal and mechanical damage to the surrounding environment. Currently, instrument designers rely heavily on empirical-based strategies to understand tool-bone interactions, with significant amounts of prototyping and validation experiments required throughout the design process. The aim of this study is to develop an experimentally-validated predictive computational model of orthopaedic cutting processes in three dimensions to understand the role of various cutting parameters on cutting forces and chip formation. An experimental model of orthogonal cutting was developed, whereby an adaptable cutting tool fixture driven by a servo-hydraulic uniaxial test machine was used to carry out high-rate cutting tests on Sawbone® trabecular bone analogues. A three-dimensional computational model was also developed using Abaqus/Explicit. The constitutive model describing material behaviour considers strain-rate and pressure-dependant yield behaviour using a Drucker-Prager elastic-plastic damage model, with Strain-hardening and rate-dependent model constants determined through dynamic uniaxial high-strain rate compression tests of material cubes. An excellent correlation between experimental and computational models was found, with the computational model accurately predicting tool cutting forces and chip development ahead of the tool during the cutting process. It was identifying that lower tool rake-angles resulted in the formation of larger discontinuous chips and higher cutting forces, while higher rake angles tended to lead to more continuous chip formation and lower cutting forces

Abstract. Background. The aim of the present experimental study was to analyse vancomycin elution kinetics of nine bone fillers used in orthopaedic and trauma surgery over 42 consecutive days. Methods. Two allograft bone chips (carriers 1 and 2), a calcium-sulfate matrix (carrier 3), a hydroxyapatite/calcium-sulphate composite (carrier 4), four bone cements (carriers 5-8) and a pure tricalcium phosphate matrix (carrier 9), either already contained vancomycin, or were mixed with it following manufacturer's recommendations. Over 42 days, half of elution medium was substituted by the same amount of PBS at 9 distinct time points. Vancomycin concentration in obtained samples were measured with a kinetic microparticle immunoassay, and masses consecutively calculated. To enhance comparability between carriers analysed, vancomycin mass released related to overall mass within each probe was determined. Notably, elution kinetics of carriers 1 to 4 have been published previously. Results. All carriers initially released high vancomycin masses, followed by constant reduction later into the experiment. Mean initial vancomycin masses released after 4 hours were highest for carriers 1 (337.7 ± 76.2 mg), 9 (68.4 ± 4.9 mg), and 2 (49.0 ± 54.6 mg). From prefinal (35 days) to last measurement (42 days) carriers 2 (8.6 ± 4.8 mg), 1 (2.4 ± 1.0 mg), and 5 (0.1 ± 0.1 mg) had released highest vancomycin masses. Notably, all five bone cements tested only released a small percental amount of their total mass up to the last measurement (42 days; 2.1% – 9.3%), whilst allografts and resorbable synthetic bone fillers discarded high percental values (22.5% – 79.2%). Conclusions. Elution kinetics differ between 9 antibiotic-loaded bone fillers, with high vancomycin masses released by allografts and resorbable bone fillers over time. Transferred to clinical practice, these may be favoured over bone cements in case prolonged and high antibiotic release is warranted rather than mechanical stability

Aim. Aim of this monocentric, prospective study was to evaluate the safety, efficacy, clinical and radiographical results at 24-month follow-up (N = 6 patients) undergoing hip revision surgery with severe acetabular bone defects (Paprosky 2C-3A-3B) using a combination of a novel phase-pure betatricalciumphosphate - collagen 3D matrix with allograft bone chips. Method. Prospective follow-up of 6 consecutive patients, who underwent revision surgery of the acetabular component in presence of massive bone defects between April 2018 and July 2019. Indications for revision included mechanical loosening in 4 cases and history of hip infection in 2 cases. Acetabular deficiencies were evaluated radiographically and CT and classified according to the Paprosky classification. Initial diagnosis of the patients included osteoarthritis (N = 4), a traumatic fracture and a congenital hip dislocation. 5 patients underwent first revision surgery, 1 patient underwent a second revision surgery. Results. All patients were followed-up radiographically with a mean of 25,8 months. No complications were observed direct postoperatively. HHS improved significantly from 23.9 preoperatively to 81.5 at the last follow-up. 5 patients achieved a defined good result, and one patient achieved a fair result. No periprosthetic joint infection, no dislocations, no deep vein thrombosis, no vessel damage, and no complaint about limbs length discrepancy could be observed. Postoperative dysmetria was found to be + 0.2cm (0cm/+1.0cm) compared to the preoperative dysmetria of − 2.4 cm (+0.3cm/−5.7cm). Conclusions. Although used in severe acetabular bone defects, the novel phase-pure betatricalciumphosphate - collagen 3D matrixshowed complete resorption and replacement by newly formed bone, leading to a full implant integration at 24 months follow-up and thus represents a promising method with excellent bone regeneration capacities for complex cases, where synthetic bone grafting material is used in addition to autografts

Abstract. Introduction. Risk factors for osteoarthritis include raised BMI and female gender. Whether these two factors influenced synovial gene expression was investigated using a triangulation and modelling strategy which generated 12 datasets of gene expression in synovial tissue from three knee pathologies with matching BMI groups, obese and overweight, and gender distributions. Methodology. Intra-operative synovial biopsies were immersed in RNAlater at 4oC before storage at -80oC. Total RNA was extracted using RNAeasy with gDNA removal. Following RT- PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Linear models were prepared in limma with gender and BMI factors incorporated sequentially for each pathology comparison, generating 12 models of probes differentially expressed at FDR p<0.05 and Bayes number, B>0. Data analysis of differently expressed genes utilized Ingenuity Pathway Analysis and Cytoscape with Cluego and Cytohubba plug-ins. Results. Expression of 453 synovial genes was influenced by BMI and gender, 360 encode proteins such as HIF-1a, HSF1, HSPA4, HSPA5. Top canonical pathways include Unfolded protein response, Protein Ubiquiitation and Clathrin mediated endocytosis signalling linked by modulation of heat shock proteins, comparable to pathology dependent regulation. In addition BMI and gender modulate gene expression in the NRF2-mediated oxidative stress response pathway with down regulation of Glutathione-S-transferases potentially down regulating antioxidant defences. Conclusion. The enhanced risk of osteoarthritis induced by an elevated BMI and female gender maybe include differential expression of heat shock proteins and genes in the NRF2 pathway

Abstract. Introduction. It is increasingly evident that synovium may play a larger role in the aetiology of osteoarthritis. We compared gene expression in whole tissue synovial biopsies from end-stage knee osteoarthritis and knee trauma patients with that of their paired explant cultures to determine how accurately cultured cells represent holistic synovial function. Methodology. Synovial tissue biopsies were taken from 16 arthroplasty patients and 8 tibial plateau fracture patients with no osteoarthritis. Pairs of whole tissue fragments were either immediately immersed in RNAlater Stabilisation Solution at 4o C before transfer to -80o C storage until RNA extraction; or weighed, minced and cultured at 500mg tissues/5ml media in a humidified incubator at 37oC, 5% CO2. After sub-culturing total RNA was extracted using RNAeasy Plus Mini Kit with gDNA removal. Following RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Results. PCA analysis illustrates the clear separation of expression array data from cultured cells compared with their parental whole tissues and no segregation between cells derived from osteoarthritic or trauma tissues. A differentially expressed gene heat map demonstrated the hierarchical independence of cultured cells from their paired sample parental tissues. The biological pathways enriched by these gene expression differences emphasise the activities of macrophages and lymphocytes lost from culture. Conclusion. Adherent synovial cells grown from different knee pathologies lose the expression patterns characteristic of their originating pathology. Interpretation of data needs caution as the cells are not representative of whole synovium

Abstract. Introduction. Synovitis impacts osteoarthritis symptomatology and progression. The transcription factors controlling synovial gene expression have not been described. This study analyses gene expression in synovium samples from 16 patients with osteoarthritis with 9 undergoing arthroscopic and 8 knee trauma surgery for non-arthritic pathologies. Methodology. Intra-operative synovial biopsies were immersed in RNAlater at 4oC before storage at -80oC. Total RNA was extracted using RNAeasy. After purification, RT-PCR and quality assessment, cDNA was applied to Affymetrix Clariom D microarray gene chips. Bioinformatics analyses were performed. Linear models were prepared in limma with gender and BMI factors incorporated sequentially for each pathology comparison, generating 12 models of probes differentially expressed at FDR p<0.05 and Bayes number, B>0. Data analysis of differently expressed genes utilized Ingenuity Pathway Analysis and Cytoscape with Cluego and Cytohubba plug-ins. Results. Amongst the 2084 genes with significantly differential expression (DEG), 135 had transcription regulator capabilities and 121 a nuclear location. IPA analysis of OATKR and arthroscopic tissue comparison DEG identified 12 nuclear transcription factors linked to 31 DEG whose encoded proteins located within cytoplasmic and cell membrane compartments. All 12 were significantly up-regulated and acting in pathways up-regulating transcription of DNA and RNA, cell survival and angiogenesis while down-regulating senescence and apoptosis. NFE2L2, integral to the TGF-beta signalling pathway, was identified as a bottleneck gene. Conclusion. This analysis indicates the complexity of synovial gene expression regulation and offers target genes and pathways for evaluation during osteoarthritis pathogenesis

Femoral revision after cemented total hip arthroplasty (THA) might include technical difficulties, following essential cement removal, which might lead to further loss of bone and consequently inadequate fixation of the subsequent revision stem. Bone loss may occur because of implant loosening or polyethylene wear, and should be addressed at time of revision surgery. Stem revision can be performed with modular cementless reconstruction stems involving the diaphysis for fixation, or alternatively with restoration of the bone stock of the proximal femur with the use of allografts. Impaction bone grafting (IBG) has been widely used in revision surgery for the acetabulum, and subsequently for the femur in Paprosky defects Type 1 or 2. In combination with a regular length cemented stem, impaction grafting allows for restoration of femoral bone stock through incorporation and remodeling of the proximal femur. Cavitary bone defects affecting the metaphysis and partly the diaphysis leading to a wide femoral canal are ideal indications for this technique. In case of combined segmental-cavitary defects a metal mesh is used to contain the defect which is then filled and impacted with bone grafts. Cancellous allograft bone chips of 2 to 4 mm size are used, and tapered into the canal with rods of increasing diameters. To impact the bone chips into the femoral canal a dummy of the dimensions of the definitive cemented stem is inserted and tapped into the femur to ensure that the chips are firmly impacted. Finally, a standard stem is implanted into the newly created medullary canal using bone cement. To date several studies from Europe have shown favorable results with this technique, with some excellent long-term results reported. Advantages of IBG include the restoration of the bone stock in the proximal femur, the use of standard length cemented stems and preserving the diaphysis for re-revision. As disadvantages of the technique: longer surgical time, increased blood loss and the necessity of a bone bank can be mentioned

Previous studies have described an age-dependent distortion of bone microarchitecture for α-CGRP-deficient mice (3). In addition, we observed changes in cell survival and activity of osteoblasts and osteoclasts isolated from young wildtype (WT) mice when stimulated with α-CGRP whereas loss of α-CGRP showed only little effects on bone cell metabolism of cells isolated from young α-CGRP-deficient mice. We assume that aging processes differently affect bone cell metabolism in the absence and presence of α-CGRP. To further explore this hypothesis, we investigated and compared cell metabolism of osteoblasts and bone marrow derived macrophages (BMM)/osteoclast cultures isolated from young (8–12 weeks) and old (9 month) α-CGRP-deficient mice and age matched WT controls. Isolation/differentiation of bone marrow macrophages (BMM, for 5 days) to osteoclasts and osteoblast-like cells (for 7/14/21 days) from young (8–12 weeks) and old (9 month) female α-CGRP−/− and WT control (both C57Bl/6J) mice according to established protocols. We analyzed cell migration of osteoblast-like cells out of femoral bone chips (crystal violet staining), proliferation (BrdU incorporation) and caspase 3/7-activity (apoptosis rate). Alkaline phosphatase (ALP) activity reflects osteoblast bone formation activity and counting of multinucleated (≥ 3 nuclei), TRAP (tartrate resistant acid phosphatase) stained osteoclasts reflects osteoclast differentiation capacity. We counted reduced numbers of BMM from young α-CGRP−/− mice after initial seeding compared to young WT controls but we found no differences between old α-CGRP−/− mice and age-matched controls. Total BMM number was higher in old compared to young animals. Migration of osteoblast-like cells out of bone chips was comparable in both, young and old α-CGRP−/− and WT mice, but number of osteoblast-like cells was lower in old compared to young animals. Proliferation of old α-CGRP−/− BMM was higher when compared to age-matched WT whereas proliferation of old α-CGRP−/− osteoblasts after 21 days of osteogenic differentiation was lower. No differences in bone cell proliferation was detected between young α-CGRP−/− and age-machted WT mice. Caspase 3/7 activity of bone cells from young as well as old α-CGRP−/− mice was comparable to age-matched controls. Number of TRAP-positive multinucleated osteoclasts from young α-CGRP−/− mice was by trend higher compared to age-matched WT whereas no difference was observed in osteoclast cultures from old α-CGRP−/− mice and old WT. ALP activity, as a marker for bone formation activity, was comparable in young WT and α-CGRP−/− osteoblasts throughout all time points whereas ALP activity was strongly reduced in old α-CGRP−/− osteoblasts after 21 days of osteogenic differentiation compared to age-matched WT. Our data indicate that loss of α-CGRP results in a reduction of bone formation rate in older individuals caused by lower proliferation and reduced activity of osteogenic cells but has no profound effects on bone resorption rate. We suggest that the osteopenic bone phenotype described in aged α-CGRP-deficient mice could be due to an increase of dysfunctional matured osteoblasts during aging resulting in impaired bone formation