Periprosthetic Inflammation Research Articles

Mitigating polyethylene-mediated periprosthetic tissue inflammation through MEDSAH-grafting

Mitigating polyethylene-mediated periprosthetic tissue inflammation through MEDSAH-grafting

The role of culture-negative infection among infectious complications after total knee arthroplasty

Introduction Diagnosis of chronic periprosthetic joint infection (PJI) is difficult with the clinical signs of periprosthetic inflammation showing no growth of microorganism in the biomaterial. The frequency of culture-negative infection can reach 42.1 %. The objective of the study was to analyze outcomes of two-stage treatment of chronic PJI of the knee joint depending on the etiology of the infectious process.Material and methods A retrospective analysis of outcomes was produced for 103 patients: group I (n=30) showing no growth of microorganisms and group II (n = 73) demonstrating positive growth of pathogens. Knee PJI was diagnosed according to the 2018 ICM criteria. A favorable outcome suggested absence of recurrence for at least two years after reimplantation of endoprosthesis, arthrodesis, “life with a spacer” without signs of infection.Results Culture-negative infection was detected in 29.1 % (n = 30). Patients in the group were 1.5 times more likely to receive antibiotic therapy prior to admission and had average levels of CRP, ESR and articular leukocyte count being 1.5-2 times less than those in group II. Staphylococci (69.8 %) including MRSE (75 %) was the leading pathogen in group II. Recurrence of infection was 3.4 % in group I and 16.9 % in group II (p = 0.0928), the two-stage treatment was successful in 96.7 % and 74 %, respectively (p = 0.0064).Discussion Causes for the lack of growth of microorganisms in biological materials included previous antibiotic therapy, wound drainage, violations of the rules for sampling of biological material, absence of media for the growth of atypical microorganisms and the ability of microorganisms to form biofilms on implant surfaces. An emergency histological examination of the affected tissues was practical during surgery in doubtful situations for adequate surgical approach. The results of a meta-analysis (2023) showed that the replacement of an infected endoprosthesis was more effective for the treatment of a culture-negative infection compared to debridement and preservation of implant.Conclusion The culture-negative infection group in our series showed better success rate of a two-stage treatment of PJI using implant replacement and broad-spectrum empiric antibiotic therapy at a two-year follow-up period. The negative microbiological result in the group could be caused by antibacterial drugs administered prior to diagnosis of PJI.

The hypotheses of oral disease-associated perioprosthetic joint infections to understand the role of oral health for endoprostheses - a narrative review.

Periprosthetic infections are a severe complication, causing enormous morbidity. The role of oral diseases in the development of such infections has been discussed controversially, showing a large discrepancy between prevalence of oral foci and infections of endoprostheses (EP). This narrative review aimed in explaining and discussing two hypotheses for the occurrence of oral disease-associated EP infections. The hypotheses include two mechanisms. (1) In case of an acute exacerbation during the early healingperiod after EP surgery (first 3 months). (2) Coincidental in the context of late EP infections (after successful initial healing), where an initial periprosthetic inflammation can be colonized secondarily by oral microorganisms. In both settings,oral foci are not primarily causative for EP infection, but represent an important reservoir for EP colonization, while the immunological conditions (locally and systemically) are crucial for the onset of an EP infection. As potential consequence, patients with risk factors should be orally rehabilitated prior to EP surgery. Usage of antibiotic prophylaxis during the first 3 months after EP implantation (initial healing period) might be considered, but has no reliable evidence. To avoid morbidity of patients, radical dental clearance is unfavorable for the respective patients. Altogether, patients with EP should receive increased attention from the dental perspective alongside with dental preventive measures, because they show a high dental and periodontal treatment need.

Attenuating Chronic Fibrosis: Decreasing Foreign Body Response with Acellular Dermal Matrix.

Surgical implants are increasingly used across multiple medical disciplines, with applications ranging from tissue reconstruction to improving compromised organ and limb function. Despite their significant potential for improving health and quality of life, biomaterial implant function is severely limited by the body's immune response to its presence: this is known as the foreign body response (FBR) and is characterized by chronic inflammation and fibrotic capsule formation. This response can result in life-threatening sequelae such as implant malfunction, superimposed infection, and associated vessel thrombosis, in addition to soft tissue disfigurement. Patients may require frequent medical visits, as well as repeated invasive procedures, increasing the burden on an already strained health care system. Currently, the FBR and the cells and molecular mechanisms that mediate it are poorly understood. With applications across a wide array of surgical specialties, acellular dermal matrix (ADM) has emerged as a potential solution to the fibrotic reaction seen with FBR. Although the mechanisms by which ADM decreases chronic fibrosis remain to be clearly characterized, animal studies across diverse surgical models point to its biomimetic properties that facilitate decreased periprosthetic inflammation and improved host cell incorporation. Impact Statement Foreign body response (FBR) is a significant limitation to the use of implantable biomaterials. Acellular dermal matrix (ADM) has been observed to decrease the fibrotic reaction seen with FBR, although its mechanistic details are poorly understood. This review is dedicated to summarizing the primary literature on the biology of FBR in the context of ADM use, using surgical models in breast reconstruction, abdominal and chest wall repair, and pelvic reconstruction. This article will provide readers with an overarching review of shared mechanisms for ADM across multiple surgical models and diverse anatomical applications.

Ceramic-on-Ceramic Bearings in Total Joint Arthroplasty. Part 1

Summary. Ceramic bearings were first employed as alternatives to polyethylene (PE) bearings in total joint arthroplasty about a decade after Sir John Charnley introduced the first durable total hip arthroplasty (THA) with a metal-PE articulation. Charnley’s approach was based on a metal stem bonded to bone with polymethylmethacrylate (PMMA) and an acetabular component made of ultra-high-molecular-weight PE (UHMWPE). Microscopic particulate debris in the joint space from bearing wear has been shown to lead to periprosthetic inflammation, osteolysis, and implant loosening. Cross-linking can reduce the wear of UHMWPE, but it also compromises UHMWPE’s mechanical properties. Accordingly, there are concerns related to potential brittleness if UHMWPE implants are not positioned optimally. Also, the smaller particles generated from cross-linked UHMWPE may present an increased particulate load in vivo. Thus, there is a need for data on the long-term outcomes of cross-linked UHMWPE. Any technology that can reduce bearing wear rates in THA and total knee arthroplasty (TKA) can potentially decrease the morbidity and risks associated with premature revision surgery related to wear. Improved wear resistance also allows the use of large-diameter femoral heads in THA, leading to increased arc of movement and less risk of prosthesis dislocation. The ideal joint bearing for THA and TKA would be able to withstand high cyclic loading for several decades without undergoing corrosion or fretting at modular metal tapers, and would possess proven biocompatibility and material stability in vivo, as well as ultralow wear rates. The search for the ideal total joint bearing has led to the development of ceramic bearings.

Targeting thymidine phosphorylase as a potential therapy for bone loss associated with periprosthetic osteolysis.

Macrophages are generally thought to play a key role in the pathogenesis of aseptic loosening through initiating periprosthetic inflammation and pathological bone resorption. The aim of this study was to identify macrophage‐derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage‐derived factors that were identified by RNA‐seq analysis of stimulated macrophages on osteoclast differentiation. Surprisingly, thymidine phosphorylase (TYMP) was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP knockdown reduced the number of osteoclasts in macrophages that had been stimulated with polyethylene debris. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. The RNA‐seq for TYMP‐induced‐osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris‐induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis.

Identification of Thymidine Phosphorylase as a Potential Therapeutic Target for Bone Loss Associated Periprosthetic Osteolysis

Background: Macrophage-derived factors are generally thought to play a key role in the pathogenesis of aseptic loosening though initiating periprosthetic inflammation and pathological bone resorption. Therefore, the aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. Methods: We examined the effects of 12 macrophage-derived factors that were identified by RNA sequencing analysis of stimulated macrophages on osteoclast differentiation in vitro. The identified molecule was characterized as osteoclastogenic factor in vitro and in vivo. RNA-seq for the induced-osteoclasts was performed in an effort to understand its action mode. Therapeutic effects of Src kinase inhibitor were evaluated in implant particles-induced osteolysis murine model. Findings: Thymidine phosphorylase (TYMP) was found to induce the production of significant numbers of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP silencing by siRNA reduced the number of osteoclasts in macrophages that had been stimulated with implant particles, suggesting a potential role in periprosthetic osteolysis. High levels of TYMP were detected in the serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. Interestingly, TYMP stimulation appeared to activate the tyrosine kinase Fyn signaling associated with cell fusion and osteoclast formation. The oral administration of saracatinib, an FYN kinase inhibitor, significantly and consistently suppressed the formation of bone osteolytic lesions in implant wear particles-induced osteolysis model. Interpretation: Our findings highlight a novel molecular target for therapeutic intervention in implant loosening. Funding Information: Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research C;17K10993), Akiyama Life Science, Foundation and Kobayashi Foundation, and Japan Agencyfor Medical Research and Development (JP20gm6210004). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The institutional review boards of Hokkaido University and hospital approved the study protocols for the use of human samples (approval ID: 016-0002). All participants signed an informed consent form for research use. Procedures for animal experiments were performed following protocols approved by the Institute of Animal Care and Use Committee of the Hokkaido University Graduate School of Medicine (no. 17-0085).

Progressive loss of implant fixation in a preclinical rat model of cemented knee arthroplasty.

Aseptic loosening of total knee arthroplasty continues to be a challenging clinical problem. The progression of the loosening process, from the initial well-fixed component, is not fully understood. In this study, loss of fixation of cemented hemiarthroplasty was explored using 9-month-old Sprague-Dawley rats with 0, 2, 6, 12, 26 week end points. Morphological and cellular changes of cement-bone fixation were determined for regions directly below the tibial tray (epiphysis) and distal to the tray (metaphysis). Loss of fixation, with a progressive increase in cement-bone gap volume was found in the epiphysis (0.162 mm3 /week), but did not progress appreciably in the metaphysis (0.007 mm3 /week). In the epiphysis, there was an early and sustained elevation of osteoclasts adjacent to the cement border and development of a fibrous tissue layer between the cement and bone. There was early formation of bone around the cement in the metaphysis, resulting in a condensed bone layer without osteoclastic bone resorption or development of a fibrous tissue layer. Implant positioning was also an important factor in the cement-bone gap formation, with greater gap formation for implants that were placed medially on the tibial articular surface. Loss of fixation in the rat model mimicked patterns found in human arthroplasty where cement-bone gaps initiate under the tibial tray, at the periphery of the implant. This preclinical model could be used to study early biological response to cemented fixation and associated contributions of mechanical instability, component alignment, and periprosthetic inflammation.

The Mechanisms Underlying the Biological Response to Wear Debris in Periprosthetic Inflammation

Joint replacement surgery is the gold standard therapeutic approach to treat patients with end-stage hip and knee arthritis, providing pain relief and joint function recovery. Despite the improvements in implant design and surgical techniques, revisions after total joint replacement are expected to grow. The periprosthetic inflammation, featured by the sustained inflammatory response to the implant debris, elicits the activation of osteoclasts and consequent periprosthetic osteolysis (PPOL), ultimately leading to implant aseptic loosening (AL), which is the most common cause of long-term implant failure. There are currently no effective strategies to control periprosthetic inflammation, and long-term implant survival remains a major challenge in orthopedics. A broad knowledge of the mechanisms underlying the biological response to implant debris would support the development of novel and effective pharmacological strategies to manage PPOL and promote implant lifespan. In this review, a detailed description of the cellular and molecular mechanisms underlying the biological response to implant debris is provided, highlighting the most recent findings. Furthermore, we reviewed novel therapeutic strategies that are being investigated to prevent inflammatory periprosthetic osteolysis.

Biological acellular pericardial mesh regulated tissue integration and remodeling in a rat model of breast prosthetic implantation.

The use of biological meshes has proven beneficial in surgical restriction and periprosthetic capsular contracture following breast prosthetic-reconstruction. Three different types (smooth, texturized, and polyurethane) of silicone round mini prostheses were implanted under rat skin with or without two different bovine acellular pericardial biological meshes (APMs, BioRipar, and Tutomesh). One hundred eighty-six female rats were divided into 12 groups, sacrificed after 3, 6, and 24 weeks and tissue samples investigated by histology and immunohistochemistry. Implantation of both APMs, with or without prostheses, reduced capsular α-SMA expression and CD3+ inflammatory cell infiltration, increasing capillary density and cell proliferation, with some differences. In particular, Tutomesh was associated with higher peri-APM CD3+ inflammation, prosthetic capsular dermal α-SMA expression and less CD31+ vessels and cell proliferation compared with BioRipar. None differences were observed in tissue integration and remodeling following the APM + prostheses implantation; the different prostheses did not influence tissue remodeling. The aim of our study was to investigate if/how the use of different APMs, with peculiar intrinsic characteristics, may influence tissue integration. The structure of APMs critically influenced tissue remodeling after implantation. Further studies are needed to develop new APMs able to optimize tissue integration and neoangiogenesis minimizing periprosthetic inflammation and fibrosis.

Replacement of infected aortoiliac vascular grafts with bifurcated BioIntegral Surgical No-React® bovine pericardial xenografts.

The infection of a vascular prosthesis is potentially fatal, and its effective treatment still remains the greatest challenge for vascular surgeons. We present our initial experience using bovine pericardial vascular prostheses to replace infected aortoiliac vascular grafts. Six consecutive patients with infection of the graft were prospectively included in this study. Infection of the vascular graft was confirmed by clinical symptoms, laboratory tests and the results of computed tomography and positron emission tomography/computed tomography. In all cases, the infected aortoiliac graft was surgically removed and replaced by the bovine-pericardial BioIntegral aortic-bifemoral prosthesis. Technical success was achieved in every case with no in-hospital or 30days mortality. One patient required revision of distal anastomosis due to recurrent bleeding at day four after surgery. One patient presented with upper gastrointestinal tract bleeding during the postoperative period, which was managed endoscopically. The mean hospital stay was 14days (range 9-19). The control CT scan performed 2months after surgery showed significant regression of abscesses and periprosthetic inflammation. Two patients died within 32months of follow-up: one due to heart attack, the other due to generalized sepsis, which was correlated with the previous infection. Four patients are still in follow-up. The BioIntegral prosthesis is patent in all four cases, with no clinical or ultrasonographic signs of infection. Our brief investigation shows that a bovine pericardial prosthesis may be a valuable option in the treatment of vascular grafts infections.

Sterile particle-induced inflammation is mediated by macrophages releasing IL-33 through a Bruton’s tyrosine kinase-dependent pathway

Initiation of the innate sterile inflammatory response that can develop in response to microparticle exposure is little understood. Here, we report that a potent type 2 immune response associated with the accumulation of neutrophils, eosinophils and alternatively activated (M2) macrophages was observed in response to sterile microparticles similar in size to wear debris associated with prosthetic implants. Although elevations in interleukin-33 (IL-33) and type 2 cytokines occurred independently of caspase-1 inflammasome signalling, the response was dependent on Bruton's tyrosine kinase (BTK). IL-33 was produced by macrophages and BTK-dependent expression of IL-33 by macrophages was sufficient to initiate the type 2 response. Analysis of inflammation in patient periprosthetic tissue also revealed type 2 responses under aseptic conditions in patients undergoing revision surgery. These findings indicate that microparticle-induced sterile inflammation is initiated by macrophages activated to produce IL-33. They further suggest that both BTK and IL-33 may provide therapeutic targets for wear debris-induced periprosthetic inflammation.

Modern Primary Breast Augmentation: Best Recommendations for Best Results.

After reading this article, the participant should be able to: 1. Develop a practical method for preoperative implant size selection. 2. List characteristics and examples of fourth- and fifth-generation silicone implants. 3. Recognize the differences in "profile" designations across implant manufacturers. 4. Recall updated statistics on breast implant-associated anaplastic large cell lymphoma and describe current guidelines on disease diagnosis and treatment. 5. Apply atraumatic and aseptic surgical techniques in primary breast augmentation. Modern primary breast augmentation requires an intimate knowledge of the expanding breast implant market, including characteristics of current generation silicone implants and "profile" types. Optimal implant size selection requires balancing patient desires with tissue qualities. Evidence and awareness of breast implant-associated anaplastic large cell lymphoma continue to grow, and patients and surgeons alike should be informed on the most updated facts of the disease entity. Atraumatic surgical technique and aseptic adjuncts are critical in reducing periprosthetic inflammation and contamination, both of which are known instigators of capsular contracture and potentially breast implant-associated anaplastic large cell lymphoma.

Interplay between sympathetic nervous system and inflammation in aseptic loosening of hip joint replacement

Inflammation is a common symptom in joint disorders such as rheumatoid arthritis, osteoarthritis (OA) and implant aseptic loosening (AL). The sympathetic nervous system is well known to play a critical role in regulating inflammatory conditions, and imbalanced sympathetic activity has been observed in rheumatoid arthritis. In AL it is not clear whether the sympathetic nervous system is altered. In this study we evaluated the systemic and local profile of neuroimmune molecules involved in the interplay between the sympathetic nervous system and the periprosthetic inflammation in hip AL. Our results showed that periprosthetic inflammation does not trigger a systemic response of the sympathetic nervous system, but is mirrored rather by the impairment of the sympathetic activity locally in the hip joint. Moreover, macrophages were identified as key players in the local regulation of inflammation by the sympathetic nervous system in a process that is implant debris-dependent and entails the reduction of both adrenergic and Neuropetide Y (NPY)-ergic activity. Additionally, our results showed a downregulation of semaphorin 3A (SEMA3A) that may be part of the mechanism sustaining the periprosthetic inflammation. Overall, the local sympathetic nervous system emerges as a putative target to mitigate the inflammatory response to debris release and extending the lifespan of orthopedic implants.

Dysregulated expression of antioxidant enzymes in polyethylene particle-induced periprosthetic inflammation and osteolysis.

Small wear particles (0.1–10 μm) in total joint replacement are generally considered as the major causative agent leading to periprosthetic inflammation and osteolysis. However, little is known about the roles of larger wear particles (10–100 μm) in periprosthetic inflammation and osteolysis. Additionally, although ample studies demonstrated that increased oxidative stress is critically involved in particle-induced inflammation and osteolysis, detailed changes in antioxidant enzymes expression in the disease development remain largely unclear. Herein, we used a rat knee prosthesis model to assess effects of polyethylene (PE) particles (20–60 μm) on the levels of oxidative stress markers such as malondialdehyde (MDA) and total antioxidant capacity (TAC) in blood plasma, and on the expression profiles of antioxidant enzymes in knee joint tissues. In combination with a forced-exercise intervention for all surgical rats, we found that the rat groups treated with both artificial joint and PE particles exhibited higher MDA levels and lower TAC levels, together with lower levels of physical activity and higher levels of inflammatory markers, than the sham group and the groups receiving artificial joint or PE particles alone at weeks 20–24 post-operatively. Dose-response relationships between the exposure to PE particles and the induction of oxidative stress and inflammation were also observed in the artificial joint/PE groups. Under such conditions, we unexpectedly found that most of antioxidant enzymes displayed pronounced up-regulation, with concomitant induction of inflammatory and osteoclast-inducing factors (including IL-1β, NF-κB and RANKL), in the artificial joint/PE groups as compared to the sham, artificial joint only, or PE only group. Only a few antioxidant enzymes including SOD2 and GPx2 showed down-regulation. Collectively, our findings demonstrate that implantation of artificial joint along with large PE particles synergistically trigger the induction of oxidative stress; however, down-regulation of many antioxidant enzymes may not necessarily occur during the disease development.

Breast implant-associated anaplastic large cell lymphoma vs. anaplastic large cell lymphoma in a patient with breast implant effusion history: a diagnostic dilemma

Breast implant-associated anaplastic large cell lymphoma is a rare tumor, affecting patients in the post-breast implant setting, first reported in 1997. We report an extraordinary case of anaplastic large cell lymphoma presenting not as a breast mass but as a spinal tumor, and thus in distant disease stage if considered breast implant-associated. A 35-year-old female, who had undergone bilateral breast augmentations over a decade ago and recent implant removal, complained of back pain with an anterior thoracic projection bilaterally. Clinical and radiological work-up revealed pleural nodules, T6 vertebral/costal infiltration, enlarged left axillary lymph nodes, and extradural spinal masses bilaterally, from which tumor samples were studied morphologically and immunohistochemically. There was diffuse infiltration by enlarged, neoplastic lymphoid cells with eosinophilic cytoplasm and large, irregular, partially embryoid, or multi-lobulated nuclei with distinctive nucleoli. The findings were interpreted as soft tissue and bone infiltration by an aggressive CD30+, ALK− anaplastic large cell lymphoma. Since cytological or histological analysis on the initial peri-prosthetic inflammation tissue and effusion was not performed, the diagnosis of breast implant-associated anaplastic large cell lymphoma is critically difficult. If the clinical setting is not regarded coincidental, then it strongly favors the diagnosis of what could be a rare aggressive undetected form of breast implant-associated anaplastic large cell lymphoma. If so, the importance of awareness of this probable clinical entity among female patients and their surgeons as well as of the recognition and cytological study of peri-prosthetic effusions is emphasized, so as to enable early detection of a possible lymphomatous proliferation.

NF-κB decoy oligodeoxynucleotide inhibits wear particle-induced inflammation in a murine calvarial model.

Wear particles induce periprosthetic inflammation and osteolysis through activation of nuclear factor kappa B (NF-κB), which up-regulates the downstream target gene expression for proinflammatory cytokines in macrophages. It was hypothesized that direct suppression of NF-κB activity in the early phases of this disorder could be a therapeutic strategy for preventing the inflammatory response to wear particles, potentially mitigating osteolysis. NF-κB activity can be suppressed via competitive binding with double stranded NF-κB decoy oligodeoxynucleotides (ODNs) that blocks this transcription factor from binding to the promoter regions of targeted genes. In this murine calvarial study, clinically relevant polyethylene particles (PEs) with/without ODN were subcutaneously injected over the calvarial bone. In the presence of PE particles, macrophages migrated to the inflammatory site and induced tumor necrosis factor alpha (TNF-α) and receptor activator of nuclear factor kappa B ligand (RANKL) expression, resulting in an increase in the number of osteoclasts. Local injections of ODN mitigated the expression of TNF-α, RANKL, and induced the expression of two anti-inflammatory, antiresorptive cytokines: interleukin-1 receptor antagonist and osteoprotegerin. Local intervention with NF-κB decoy ODN in early cases of particle-induced inflammation in which the prosthesis is still salvageable may potentially preserve periprosthetic bone stock.

Human plasma protein adsorption onto alumina nanoparticles relevant to orthopedic wear.

Wear of ceramic orthopedic devices generates nanoparticles in vivo that may present a different biological character from the monolithic ceramic from which they are formed. The current work investigated protein adsorption from human plasma on alumina nanoparticles and monolithic samples representative of both wear particles and the ceramic components as implanted. A physicochemical characterization of the particles and their dispersion state was carried out, and the protein adsorption profiles were analyzed using 1D SDS-PAGE and mass spectrometry. Significant differences in protein-binding profiles were identified where the nanoparticles selectively bound known transporter proteins rather than the more highly abundant serum proteins that were observed on the monoliths. Proteins associated with opsonization of particles were seen to be present in the protein corona of the nanoparticles, which raises questions regarding the role of wear particles in periprosthetic tissue inflammation and aseptic loosening.

Implant based differences in adverse local tissue reaction in failed total hip arthroplasties: a morphological and immunohistochemical study.

BackgroundAdverse local tissue reaction (ALTR) is characterized by periprosthetic soft tissue inflammation composed of a mixed inflammatory cell infiltrate, extensive soft tissue necrosis, and vascular changes. Multiple hip implant classes have been reported to result in ALTR, and clinical differences may represent variation in the soft tissue response at the cellular and tissue levels. The purpose of this study was to describe similarities and differences in periprosthetic tissue structure, organization, and cellular composition by conventional histology and immunohistochemistry in ALTR resulting from two common total hip arthroplasty (THA) implant classes.MethodsConsecutive patients presenting with ALTR from two major hip implant classes (N = 54 patients with Dual-Modular Neck implant; N = 14 patients with Metal-on-Metal implant) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy and cellular composition was assessed using immunohistochemistry.ResultsLength of implantation was shorter in the DMN group versus MoM THA group (21.3 [8.4] months versus 43.6 [13.8] months respectively; p < 0.005) suggesting differences in implant performance. Morphologic examination revealed a common spectrum of neo-synovial proliferation and necrosis in both groups. Macrophages were more commonly present in diffuse sheets (Grade 3) in the MoM relative to DMN group (p = 0.016). Perivascular lymphocytes with germinal centers (Grade 4) were more common in the DMN group, which trended towards significance (p = 0.066). Qualitative differences in corrosion product morphology were seen between the two groups. Immunohistochemistry showed features of a CD4 and GATA-3 rich lymphocyte reaction in both implants, with increased ratios of perivascular T-cell relative to B-cell markers in the DMN relative to the MoM group (p = 0.032).ConclusionOur results demonstrate that both implant classes display common features of neo-synovial proliferation and necrosis with a CD4 and GATA-3 rich inflammatory infiltrate. Qualitative differences in corrosion product appearance, macrophage morphology, and lymphocyte distributions were seen between the two implant types. Our data suggests that ALTR represents a histological spectrum with implant-based features.

Wear particles and ions from cemented and uncemented titanium-based hip prostheses-a histological and chemical analysis of retrieval material.

Wear debris-induced inflammation is considered to be the main cause for periprosthetic osteolysis in total hip replacements (THR). The objective of this retrieval study was to examine the tissue reactions and exposure to metal ions and wear particles in periprosthetic tissues and blood samples from patients with titanium (Ti)-based hip prostheses that were revised due to wear, osteolysis, and/or aseptic loosening. Semiquantitative, histological tissue evaluations in 30 THR-patients revealed numerous wear debris-loaded macrophages, inflammatory cells, and necrosis in both groups. Particle load was highest in tissues adjacent to loosened cemented Ti stems that contained mainly submicron zirconium (Zr) dioxide particles. Particles containing pure Ti and Ti alloy elements were most abundant in tissues near retrieved uncemented cups. Polyethylene particles were also detected, but accounted only for a small portion of the total particle number. The blood concentrations of Ti and Zr were highly elevated in cases with high abrasive wear and osteolysis. Our findings indicate that wear particles of different chemical composition induced similar inflammatory responses, which suggests that particle size and load might be more important than the wear particle composition in periprosthetic inflammation and osteolysis. © 2014 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B:709–717, 2015.