In vitro and in vivo evaluation of the osseointegration capacity of a polycarbonate-urethane zirconium-oxide composite material for application in a focal knee resurfacing implant.

Currently available focal knee resurfacing implants (FKRIs) are fully or partially composed of metals, which show a large disparity in elastic modulus relative to bone and cartilage tissue. Although titanium is known for its excellent osseointegration, the application in FKRIs can lead to potential stress-shielding and metal implants can cause degeneration of the opposing articulating cartilage due to the high resulting contact stresses. Furthermore, metal implants do not allow for follow-up using magnetic resonance imaging (MRI).To overcome the drawbacks of using metal based FKRIs, a biomimetic and MRI compatible bi-layered non-resorbable thermoplastic polycarbonate-urethane (PCU)-based FKRI was developed. The objective of this preclinical study was to evaluate the mechanical properties, biocompatibility and osteoconduction of a novel Bionate® 75D - zirconium oxide (B75D-ZrO2 ) composite material in vitro and the osseointegration of a B75D-ZrO2 composite stem PCU implant in a caprine animal model. The tensile strength and elastic modulus of the B75D-ZrO2 composite were characterized through in vitro mechanical tests under ambient and physiological conditions. In vitro biocompatibility and osteoconductivity were evaluated by exposing human mesenchymal stem cells to the B75D-ZrO2 composite and culturing the cells under osteogenic conditions. Cell activity and mineralization were assessed and compared to Bionate® 75D (B75D) and titanium disks. The in vivo osseointegration of implants containing a B75D-ZrO2 stem was compared to implants with a B75D stem and titanium stem in a caprine large animal model. After a follow-up of 6 months, bone histomorphometry was performed to assess the bone-to-implant contact area (BIC). Mechanical testing showed that the B75D-ZrO2 composite material possesses an elastic modulus in the range of the elastic modulus reported for trabecular bone. The B75D-ZrO2 composite material facilitated cell mediated mineralization to a comparable extent as titanium. A significantly higher bone-to-implant contact (BIC) score was observed in the B75D-ZrO2 implants compared to the B75D implants. The BIC of B75D-ZrO2 implants was not significantly different compared to titanium implants. A biocompatible B75D-ZrO2 composite approximating the elastic modulus of trabecular bone was developed by compounding B75D with zirconium oxide. In vivo evaluation showed an significant increase of osseointegration for B75D-ZrO2 composite stem implants compared to B75D polymer stem PCU implants. The osseointegration of B75D-ZrO2 composite stem PCU implants was not significantly different in comparison to analogous titanium stem metal implants.

Evaluation of the Anti-Inflammatory and Chondroprotective Effect of Celecoxib on Cartilage Ex Vivo and in a Rat Osteoarthritis Model.

OBJECTIVE: The potential chondroprotective effect of celecoxib, a nonsteroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor used to reduce pain and inflammation in knee osteoarthritis patients, is disputed. This study aimed at investigating the chondroprotective effects of celecoxib on (1) human articular cartilage explants and (2) in an in vivo osteoarthritis rat model. DESIGN: Articular cartilage explants from 16 osteoarthritis patients were cultured for 24 hours with celecoxib or vehicle. Secreted prostaglandins (prostaglandin E2, prostaglandin F2α, prostaglandin D2) and thromboxane B2 (TXB2) concentrations were determined in medium by ELISA, and protein regulation was measured with label-free proteomics. Cartilage samples from 7 of these patients were analyzed for gene expression using real-time quantitative polymerase chain reaction. To investigate the chondroprotective effect of celecoxib in vivo, 14 rats received an intra-articular injection of celecoxib or 0.9% NaCl after osteoarthritis induction by anterior cruciate ligament transection and partial medial meniscectomy (ACLT/pMMx model). Histopathological scoring was used to evaluate osteoarthritis severity 12 weeks after injection. RESULTS: Secretion of prostaglandins, target of Nesh-SH3 (ABI3BP), and osteonectin proteins decreased, whereas tissue inhibitor of metalloproteinase 2 (TIMP-2) increased significantly after celecoxib treatment in the human (ex vivo) explant culture. Gene expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS4/5) and metalloproteinase 13 (MMP13) was significantly reduced after celecoxib treatment in human cartilage explants. Cartilage degeneration was reduced significantly in an in vivo osteoarthritis knee rat model. CONCLUSIONS: Our data demonstrated that celecoxib acts chondroprotective on cartilage ex vivo and a single intra-articular bolus injection has a chondroprotective effect in vivo.

First clinical results of 1-year follow-up of the femoral neck system for internal fixation of femoral neck fractures.

BACKGROUND: Closed reduction and internal fixation (CRIF) is the preferred treatment to retain the native joint and maintain optimal functionality in femoral neck fractures. Sliding hip screw (SHS) and cannulated hip screws (CHS) are established CRIF options. SHS offer high biomechanical stability, whereas CHS are minimally invasive. These established systems have a 17-21% failure rate. The Femoral neck system (FNS) was recently developed to combine the advantages of both predecessors. The aim of this study was to describe the first clinical experience with this novel implant with special emphasis on the safety and efficacy. METHODS: During a 1-year period all patients in our level-2 trauma centre with a FNF indicated for CRIF were treated using the FNS and evaluated at 2, 6, 12 weeks, 6 months and 1 year postoperatively using patient and fracture characteristics, surgical notes and radiographic imaging. RESULTS: Thirty-four patients were included, mean age was 63 years (SD 8), 58.2% was female. Fractures were classified as Pauwels I (n = 10), Pauwels II (n = 15), Pauwels III (n = 9), Garden I (n = 1), Garden II (n = 17), Garden III (n = 12) and Garden IV (n = 4). Eight reoperations were reported after 1-year follow-up; osteosyntheses failed in 6 patients due to avascular necrosis (n = 4) and cut-out (n = 2). In two patients the implant was removed due to inexplicable pain. Age (< 65 years) was related to lower risk for failure. There was a trend for females having more failures. CONCLUSION: This study indicates that the FNS is a potential safe and effective CRIF modality. Age (< 65 years) is an important factor to keep in mind when selecting patients for CRIF as it is related to lower risk for failure. Future long-term follow-up studies with larger populations should indicate if functional results and risk factors for failure are comparable to SHS or CHS.

Failure Mode Analysis of an Exeter Stem Fracture Initiated at the Introducer Hole: Time for a Design Change?

The fracturing of a hip prosthesis stem at its neck, in the absence of a trauma, is an extremely rare but serious adverse event. The patient in our case was young, active, and tall, thereby putting high mechanical loads on the prosthesis. Radiographs of the initial procedure and blood and synovium analysis showed no abnormalities. Analysis of the stem revealed niobium-rich precipitates, that is, alloy artifacts, at the introducer stud hole. The mechanically vulnerable location of the introducer stud hole, combined with alloy artifacts at that location and high mechanical stress, ultimately led to failure of the prosthesis. As younger and heavier patients will demand hip arthroplasty in the future, simple stem design adaptations should be considered to prevent stem fractures at the introducer stud hole.

A Systematic Review of Focal Cartilage Defect Treatments in Middle-Aged Versus Younger Patients.

BACKGROUND: Focal cartilage defects are often debilitating, possess limited potential for regeneration, are associated with increased risk of osteoarthritis, and are predictive for total knee arthroplasty. Cartilage repair studies typically focus on the outcome in younger patients, but a high proportion of treated patients are 40 to 60 years of age (ie, middle-aged). The reality of current clinical practice is that the ideal patient for cartilage repair is not the typical patient. Specific attention to cartilage repair outcomes in middle-aged patients is warranted. PURPOSE: To systematically review available literature on knee cartilage repair in middle-aged patients and include studies comparing results across different age groups. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic search was performed in EMBASE, MEDLINE, and the Cochrane Library database. Articles were screened for relevance and appraised for quality. RESULTS: A total of 21 articles (mean Coleman Methodology Score, 64 points) were included. Two out of 3 bone marrow stimulation (BMS) studies, including 1 using the microfracture technique, revealed inferior clinical outcomes in middle-aged patients in comparison with younger patients. Nine cell-based studies were included showing inconsistent comparisons of results across age groups for autologous chondrocyte implantation (ACI). Bone marrow aspirate concentrate showed age-independent results at up to 8 years of follow-up. A negative effect of middle age was reported in 1 study for both ACI and BMS. Four out of 5 studies on bone-based resurfacing therapies (allografting and focal knee resurfacing implants [FKRIs]) showed age-independent results up to 5 years. One study in only middle-aged patients reported better clinical outcomes for FKRIs when compared with biological repairs. CONCLUSION: Included studies were heterogeneous and had low methodological quality. BMS in middle-aged patients seems to only result in short-term improvements. More research is warranted to elucidate the ameliorating effects of cell-based therapies on the aging joint homeostasis. Bone-based therapies seem to be relatively insensitive to aging and may potentially result in effective joint preservation. Age subanalyses in cohort studies, randomized clinical trials, and international registries should generate more evidence for the large but underrepresented (in terms of cartilage repair) middle-aged population in the literature.

An optimized medial parapatellar approach to the goat medial femoral condyle.

Goats or sheep are the preferred animal model for the preclinical evaluation of cartilage repair techniques due to the similarity of the goat stifle joint to the human knee. The medial femoral condyle of the stifle joint is the preferred site for the assessment of articular cartilage repair, as this is the primary location for this type of lesion in the human knee. Proper surgical exposure of the medial femoral condyle is paramount to obtain reproducible results without surgical error. When applying the standard human medial arthrotomy technique on the goat stifle joint, there are some key aspects to consider in order to prevent destabilization of the extensor apparatus and subsequent postoperative patellar dislocations with associated animal discomfort. This paper describes a modified surgical technique to approach the medial femoral condyle of the caprine stifle joint. The modified technique led to satisfactory exposure without postoperative incidence of patellar luxations and no long-term adverse effects on the joint.

Chondroprotective Actions of Selective COX-2 Inhibitors In Vivo: A Systematic Review.

Knee osteoarthritis (OA) is a condition mainly characterized by cartilage degradation. Currently, no effective treatment exists to slow down the progression of OA-related cartilage damage. Selective COX-2 inhibitors may, next to their pain killing properties, act chondroprotective in vivo. To determine whether the route of administration is important for the efficacy of the chondroprotective properties of selective COX-2 inhibitors, a systematic review was performed according to the PRISMA guidelines. Studies investigating OA-related cartilage damage of selective COX-2 inhibitors in vivo were included. Nine of the fourteen preclinical studies demonstrated chondroprotective effects of selective COX-2 inhibitors using systemic administration. Five clinical studies were included and, although in general non-randomized, failed to demonstrate chondroprotective actions of oral selective COX-2 inhibitors. All of the four preclinical studies using bolus intra-articular injections demonstrated chondroprotective actions, while one of the three preclinical studies using a slow release system demonstrated chondroprotective actions. Despite the limited evidence in clinical studies that have used the oral administration route, there seems to be a preclinical basis for considering selective COX-2 inhibitors as disease modifying osteoarthritis drugs when used intra-articularly. Intra-articularly injected selective COX-2 inhibitors may hold the potential to provide chondroprotective effects in vivo in clinical studies.

In vitro and in vivo study on the osseointegration of BCP-coated versus uncoated nondegradable thermoplastic polyurethane focal knee resurfacing implants.

Focal knee resurfacing implants (FKRIs) are intended to treat cartilage defects in middle-aged patients. Most FKRIs are metal-based, which hampers follow-up of the joint using magnetic resonance imaging and potentially leads to damage of the opposing cartilage. The purpose of this study was to develop a nondegradable thermoplastic polyurethane (TPU) FKRI and investigate its osseointegration. Different surface roughness modifications and biphasic calcium phosphate (BCP) coating densities were first tested in vitro on TPU discs. The in vivo osseointegration of BCP-coated TPU implants was subsequently compared to uncoated TPU implants and the titanium bottom layer of metal control implants in a caprine model. Implants were implanted bilaterally in stifle joints and animals were followed for 12 weeks, after which the bone-to-implant contact area (BIC) was assessed. Additionally, 18F-sodium-fluoride (18F-NaF) positron emission tomography PET/CT-scans were obtained at 3 and 12 weeks to visualize the bone metabolism over time. The BIC was significantly higher for the BCP-coated TPU implants compared to the uncoated TPU implants (p = .03), and did not significantly differ from titanium (p = .68). Similar 18F-NaF tracer uptake patterns were observed between 3 and 12 weeks for the BCP-coated TPU and titanium implants, but not for the uncoated implants. TPU FKRIs with surface modifications could provide the answer to the drawbacks of metal FKRIs.

[Protruding omentum with umbilical fluid leakage in a patient with liver cirrhosis]. / Een vrouw met vetweefsel uit haar navel.

A 57 year old woman with a history of liver cirrhosis and ascites presented with serous exudate spontaneously leaking from a ruptured umbilical hernia, also known as Flood syndrome. This syndrome is a rare complication of decompensated liver cirrhosis and is associated with high mortality. In this specific case, there was also omentum protruding through the umbilical hernia which limited the outflow of ascites. Patient was successfully treated with antibiotics and consecutive open primary hernia repair without mesh implantation.

Long-term Follow-up of a Randomized Controlled Trial Comparing Scarf to Chevron Osteotomy in Hallux Valgus Correction.

BACKGROUND: Hallux valgus is one of the most common foot deformities. This long-term follow-up study compared the results of 2 widely used operative treatments for hallux valgus: the scarf and chevron osteotomy. METHODS: Conventional weight bearing anteroposterior (AP) radiographs of the foot were made for evaluating the intermetatarsal angle and hallux valgus angle. For clinical evaluation, the American Orthopaedic Foot & Ankle Society (AOFAS) rating system for the hallux metatarsophalangeal-interphalangeal scale was used together with physical examination of the foot. These data were compared with the results from the original study. The Short Form 36 questionnaire, the Manchester-Oxford Foot Questionnaire (MOXFQ), and a general questionnaire including a visual analog scale (VAS) pain score were used for subjective evaluation. The primary outcome measures were the radiologic recurrence of hallux valgus and reoperation rate of the same toe. Secondary outcome measures were the results from the radiographs and subjective and clinical evaluation. The response rate was 76% at the follow-up of 14 years; in the chevron group, 37 feet were included compared with 36 feet in the scarf group. RESULTS: Twenty-eight feet in the chevron group and 27 in the scarf group developed recurrence of hallux valgus (P = .483). One patient in the scarf group had a reoperation of the same toe compared with none in the chevron group (P = .314). Current VAS pain scores and results from the SF-36, MOXFQ, and AOFAS did not significantly differ between groups. CONCLUSION: Both techniques showed similar results after 2 years of follow-up. At 14 years of follow-up, neither technique was superior in preventing recurrence. LEVEL OF EVIDENCE: Level II, randomized controlled trial.

Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects.

Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using a wide variety of polymers, cell sources, and signaling molecules have been evaluated. We start this review with basic background information on cartilage structure, its intrinsic repair, and an overview of the cartilage repair treatments from a historical perspective. Next, we thoroughly discuss polymer construct components and their current use in commercially available constructs. Finally, we provide an in-depth discussion about construct considerations such as degradation rates, cell sources, mechanical properties, joint homeostasis, and non-degradable/hybrid resurfacing techniques. As future prospects in cartilage repair, we foresee developments in three areas: first, further optimization of degradable scaffolds towards more biomimetic grafts and improved joint environment. Second, we predict that patient-specific non-degradable resurfacing implants will become increasingly applied and will provide a feasible treatment for older patients or failed regenerative treatments. Third, we foresee an increase of interest in hybrid construct, which combines degradable with non-degradable materials.