The interplay between implant design, biomaterial characteristics, and the local microenvironment adjacent to the implant is of utmost importance for implant performance and success of the joint replacement surgery. Reactive oxygen and nitrogen species (ROS/RNS) are among the various factors affecting the host as well as the implant components. Excessive formation of ROS and RNS can lead to oxidative stress, a condition that is known to damage cells and tissues and also to affect signaling pathways. It may further compromise implant longevity by accelerating implant degradation, primarily through activation of inflammatory cells. In addition, wear products of metallic, ceramic, polyethylene, or bone cement origin may also generate oxidative stress themselves. This review outlines the generation of free radicals and

Background and purposeAseptic loosening is a major cause of failure in total ankle arthroplasty (TAA). In contrast to other total joint replacements, large periarticular cysts (ballooning osteolysis) have frequently been observed in this context. We investigated periprosthetic tissue responses in failed TAA, and performed an element analysis of retrieved tissues in failed TAA.Patients and methodsThe study cohort consisted of 71 patients undergoing revision surgery for failed TAA, all with hydroxyapatite-coated implants. In addition, 5 patients undergoing primary TAA served as a control group. Radiologically, patients were classified into those with ballooning osteolysis and those without, according to defined criteria. Histomorphometric, immunohistochemical, and elemental analysis of tissues was performed. Von Kossa staining and digital microscopy was performed on all tissue samples.ResultsPatients without ballooning osteolysis showed a generally higher expression of lymphocytes, and CD3+, CD11c+, CD20+, and CD68+ cells in a perivascular distribution, compared to diffuse expression. The odds of having ballooning osteolysis was 300 times higher in patients with calcium content >0.5 mg/g in periprosthetic tissue than in patients with calcium content ≤0.5 mg/g (p < 0.001).InterpretationThere have been very few studies investigating the pathomechanisms of failed TAA and the cause-effect nature of ballooning osteolysis in this context. Our data suggest that the hydroxyapatite coating of the implant may be a contributory factor.

Hypersensitivity reactions to implants in orthopaedic and trauma surgery are a rare but devastating complication. They are considered as a delayed-type of hypersensitivity reaction (type IV), characterized by an antigen activation of sensitized T-lymphocytes releasing various cytokines and may result in osteoclast activation and bone resorption. Potential haptens are originated from metal alloys or bone-cement. A meta-analysis has confirmed a higher probability of developing a metal hypersensitivity postoperatively and noted a greater risk of failed replacements compared to stable implants. Hypersensitivity to implants may present with a variety of symptoms such as pain, joint effusion, delayed wound/bone healing, persistent secretion, allergic dermatitis (localized or systemic), clicking noises, loss of joint function, instability and failure of the implant. Various diagnostic options have been offered, including patch testing, metal alloy patch testing, histology, lymphocyte transformation test (LTT), memory lymphocyte immunostimulation assay (MELISA), leukocyte migration inhibition test (LIF) and lymphocyte activation test (LAT). No significant differences between in vivo and in vitro methods have been found. Due to unconvincing evidence for screening methods, predictive tests are not recommended for routine performance. Infectious aetiology always needs to be excluded. As there is a lack of evidence on large-scale studies with regards to the optimal treatment option, management currently relies on individual case-by-case decisions. Several options for patients with (suspected) metal-related hypersensitivity exist and may include materials based on ceramic, titanium or oxinium or modified surfaces. Promising results have been reported, but long-term experience is lacking. More large-scaled studies are needed in this context. In patients with bone-cement hypersensitivity, the component suspected for hypersensitivity should be avoided. The development of (predictive) biomarkers is considered as a major contribution for the future.