Antibacterial and anti-inflammatory ultrahigh molecular weight polyethylene/tea polyphenol blends for artificial joint applications.

Periprosthetic joint infection (PJI) is one of the main causes for the failure of joint arthroplasty. In view of the limited clinical effect of oral/injectable antibiotics and the drug resistance problem, there is a pressing need to develop antibacterial implants with therapeutic antimicrobial properties. In this work, we prepared a highly antibacterial ultrahigh molecular weight polyethylene (UHMWPE) implant by incorporating tea polyphenols. The presence of tea polyphenols not only improved the oxidation stability of irradiated UHMWPE, but also gave it the desirable antibacterial property. The potent antibacterial activity was attributed to the tea polyphenols that produced excess intracellular reactive oxygen species and destroyed the bacterial membrane structure. The tea polyphenol-blended UHMWPE had no biological toxicity to human adipose-derived stem cells and effectively reduced bacteria-induced inflammation in vivo. These results indicate that tea polyphenol-blended UHMWPE is promising for joint replacement prostheses with multifunctionality to meet patient satisfaction.

Addition of ceftaroline fosamil or vancomycin to PMMA: An in vitro comparison of biomechanical properties and anti-MRSA efficacy.

BACKGROUND: Ceftaroline is a cephalosporin that is effective against methicillin-resistant Staphylococcus aureus (MRSA) infections. The objective of this study was to determine the feasibility of using ceftaroline-loaded Polymethyl methacrylate (PMMA) as antibiotic cement against MRSA versus vancomycin-loaded PMMA in an in vitro setting. METHODS: PMMA pellets were prepared with three separate concentrations of each of the two antibiotics tested. They were tested to determine the effect of increasing concentration of antibiotics on the biomechanical properties of PMMA and antibiotic activity by measuring the zone of inhibition and broth elution assay. RESULTS: Ceftaroline PMMA at 3 wt%, three-point bending was 37.17 ± 0.51 N ( p < 0.001) and axial loading was 41.95 N ± 0.51 ( p < 0.001). At 5-wt% vancomycin-PMMA, three-point bending was 41.65 ± 0.79 N ( p = 0.02) and axial loading was 49.49 ± 2.21 N ( p = 0.01). Stiffness of ceftroline-loaded PMMA in low and medium concentration was significantly higher than the vancomycin. The zone of inhibition for ceftaroline was higher than vancomycin. Ceftaroline at 3 wt% eluted up to 6 weeks (0.3 ± 0.1 µg/ml) above the minimum inhibitory concentration (MIC) and vancomycin at 2.5 wt% eluted up to 3 weeks, same as MIC, that is, 0.5 ± 0.0 µg/ml. CONCLUSIONS: Ceftaroline, loaded at similar concentrations as vancomycin into PMMA, is a more potent alternative based on its more favourable bioactivity and elution properties, while having a lesser effect on the mechanical properties of the cement. The use of 3-wt% ceftaroline as antibiotic laden PMMA against MRSA is recommended. It should be noted that this was an in vitro study and to determine the clinical efficacy would need prospective, controlled and randomized studies.

An Alumina Ceramic Total Talar Prosthesis for Avascular Necrosis of the Talus.

Avascular necrosis tends to occur in the talus because of poor blood supply caused by the extended coverage to the articular cartilage on its surface. Treatment is conservative in the earlier stage of this disease; however, surgical treatment is usually indicated in the advanced stage. Nonunion, leg length discrepancy, or hindfoot instability may occur in patients treated with ankle or tibio-talo-calcaneal fusion. Arthroplasty using a customized total talar prosthesis designed using the computed tomography image of contralateral talus has the potential advantages of weightbearing in the earlier postoperative phase, prevention of lower extremity discrepancy, and maintenance of joint function.

Procedure for single-stage implant retention for chronic periprosthetic infection using topical degradable calcium-based antibiotics.

INTRODUCTION: Surgical treatment using DAIR (debridement, systemic antibiotics, and implant retention) can lead to high rates of treatment success in cases of early periprosthetic joint infection (PJI) but can fail in late-onset cases. Supplementary local antibiotic therapy is not yet generally established and lacks evidence-based proof of efficacy. The aim of this study was to analyze DAIR outcomes in recurrent PJI cases and patients who are not suitable for a two-stage exchange, using additional degradable calcium-based antibiotics. METHODS: All patients fulfilled the Infectious Diseases Society of America (IDSA) guidelines for chronic late-onset PJI but were not suitable for a multistage procedure because of their individual operation risk. A total of 42 patients (mean age, 73 years) were treated using a single-stage algorithm consisting of DAIR, followed by implantation of degradable antibiotics chosen in accordance with an antibiogram. OSTEOSET® (admixed ceftriaxone/vancomycin/tobramycin) and Herafill-Gentamycin® were used as carrier systems. The follow-up period was 23 months (± SD, 10.3). The study is based on institutional review board (IRB) approval. RESULTS: The clinical entities were chronic PJI of the hip (45.2%), knee (28.6%), and knee arthrodesis (26.2%). The bacterial spectrum was composed of Staphylococcus epidermidis (29%), Staphylococcus aureus (21%), and Enterococcus faecalis (21%). 21.4% showed a combination of two or more bacteria. In 73.8%, permanent remission was achieved, while 11.9% showed chronic PJI under implant retention. Implant retention could be achieved in 85.7%. CONCLUSION: DAIR usually shows low levels of success in difficult-to-treat cases. However, we could demonstrate the successful treatment of patients with recurrent PJI (typically considered DAIR-inappropriate) using degradable antibiogram-based topical calcium-based antibiotics. Over 70% of the cases went to remission and over 85% of the implants could be retained.

Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study.

The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus, whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections.

Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo.

Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs.

Patient and procedure-specific risk factors for deep infection after primary shoulder arthroplasty.

BACKGROUND: Deep infection after shoulder arthroplasty is a diagnostic and therapeutic challenge. The current literature on this topic is from single institutions or Medicare samples, lacking generalizability to the larger shoulder arthroplasty population. QUESTIONS/PURPOSES: We sought to identify (1) patient-specific risk factors for deep infection, and (2) the pathogen profile after primary shoulder arthroplasty in a large integrated healthcare system. METHODS: A retrospective cohort study was conducted. Of 4528 patients identified, 320 had died and 302 were lost to followup. The remaining 3906 patients had a mean followup of 2.7 years (1 day-7 years). The study endpoint was the diagnosis of deep infection, which was defined as revision surgery for infection supported clinically by more than one of the following criteria: purulent drainage from the deep incision, fever, localized pain or tenderness, a positive deep culture, and/or a diagnosis of deep infection made by the operating surgeon based on intraoperative findings. Risk factors evaluated included age, sex, race, BMI, diabetes status, American Society for Anesthesiologists (ASA) score, traumatic versus elective procedure, and type of surgical implant. For patients with deep infections, we reviewed the surgical notes and microbiology records for the pathogen profile. Multivariable Cox regression models were used to evaluate the association of risk factors and deep infection. Adjusted hazard ratios and 95% CI are presented. RESULTS: With every 1-year increase in age, a 5% (95% CI, 2%-8%) lower risk of infection was observed. Male patients had a risk of infection of 2.59 times (95% CI, 1.27-5.31) greater than female patients. Patients undergoing primary reverse total shoulder arthroplasty had a 6.11 times (95% CI, 2.65-14.07) greater risk of infection compared with patients having primary unconstrained total shoulder arthroplasty. Patients having traumatic arthroplasties were 2.98 times (95% CI, 1.15-7.74) more likely to have an infection develop than patients having elective arthroplasties. BMI, race, ASA score, and diabetes status were not associated with infection risk (all p > 0.05). Propionibacterium acnes was the most commonly cultured organism, accounting for 31% of isolates. CONCLUSIONS: Younger, male patients are at greater risk for deep infection after primary shoulder arthroplasty. Reverse total shoulder arthroplasty and traumatic shoulder arthroplasties also carry a greater risk for infection. Propionibacterium acnes was the most prevalent pathogen causing infection in our primary shoulder arthroplasty population. LEVEL OF EVIDENCE: Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Patterned CoCrMo and Al2 O3 surfaces for reduced free wear debris in artificial joint arthroplasty.

Surface wear of corresponding tribological pairings is still a major problem in the application of artificial joint surgery. This study aims at developing wear reduced surfaces to utilize them in total joint arthroplasty. Using a pico-second laser, samples of medical CoCrMo metal alloy and Al2 O3 ceramic were patterned by laser material removal. The subsequent tribological investigations employed a ring-on-disc method. The results showed that those samples with modified surfaces show less mass or volume loss than those with a regular, smooth surface. Using calf serum as lubricating medium, the volume loss of the structured CoCrMo samples was eight times lower than that of regular samples. By structuring Al2 O3 surfaces, the wear volume could be reduced by 4.5 times. The results demonstrate that defined surface channels or pits enable the local sedimentation of wear debris. Thus, the amount of free debris could be reduced. Fewer abrasives in the lubricated so-called three-body-wear between the contact surfaces should result in less surface damage. Apart from direct influences on the wear behavior, less amounts of free debris of artificial joints should also be beneficial for avoiding undesired reactions with the surrounding soft tissues. The results from this study are very promising. Future investigations should involve the use of simulators meeting the natural conditions in the joint and in vivo studies with living organisms.

Inhibition of the PI3K/AKT pathway reduces tumor necrosis factor-alpha production in the cellular response to wear particles in vitro.

Joint replacement is the most effective treatment for end-stage osteoarticular disease. However, macrophage-mediated aseptic loosening of joint prosthesis severely hampers the clinical effects of joint replacement. Until now, the mechanism by which macrophages regulate the secretion of inflammatory cytokines after particle stimulation is not clear. It is well known that the PI3K/AKT pathway participates in multiple cellular processes, including cell growth, survival, and inflammation. However, whether the PI3K/AKT pathway participates in the proinflammatory response of macrophages after particle stimulation and secondary aseptic loosening is still unknown. In this study, ceramic and titanium particles of different sizes were prepared to stimulate macrophages. LY294002, a specific inhibitor of PI3K, was pretreated prior to particle stimulation. The expression of tumor necrosis factor-alpha (TNF-α) and all the subunits of PI3K and AKT were detected by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot. The result showed that LY294002 could suppress the RNA and protein expression of TNF-α in RAW264.7 cells after stimulation of different particles. The subunits of PI3K (p110ß and p85ß), followed by activation of phosphor-AKT (Ser473), participated in the regulation of activating macrophages by wear particles, ultimately resulting in the secretion of TNF-α.

[Criteria of antibacterials choice for prophylaxis and therapy of implant-associated infections in prosthetic joints].

Prosthetic joints infection is a serious medical, social and financial problem. Significant achievements in prophylaxis of such infections are well known. In cases of primary endoprosthetics of large joints, the frequency of infection in the leading world clinics is 0.5-2%. However, the approaches to the treatment of such infections are different especially with respect to the antibacterial therapy: choice of drugs, administration routes, treatment course and discontinuation. Under conditions of global growth of resistance in nosocomial pathogens, the choice of antimicrobials requires consideration not only of the formal susceptibility criteria, but also of the pharmacokinetic and pharmacodynamic indices.

Berberine inhibits lipopolysaccharide- and polyethylene particle-induced mouse calvarial osteolysis in vivo.

BACKGROUND: Wear particle-induced osteolysis could lead to the aseptic loosening of implants. Studies have suggested that endotoxins, such as lipopolysaccharides (LPS), may be the primary causes of wear particle-mediated osteolysis, and that osteolysis may originate from subclinical levels of bacterial infection. However, effective therapies against wear particles and gram-negative bacterial or LPS-induced bone resorption are limited. MATERIALS AND METHODS: In the current study, the effect of berberine on LPS- and polyethylene (PE) particle-induced osteolysis in vivo was investigated using a mouse calvarial model. Osteoclast number per bone perimeter and eroded surface per bone surface were measured. RESULTS: Berberine (10 mg/kg), injected either simultaneously with LPS or 3 d after LPS (25 mg/kg) treatment, blocked LPS-induced osteoclast recruitment and bone resorption in the mouse calvarial model. A daily single-dose of berberine (10 mg/kg), injected either simultaneously with PE particles or 4 d after treatment with PE particles, blocked PE particle-induced osteoclast recruitment and bone resorption. Berberine treatment markedly decreased LPS and PE particle-induced osteoclast recruitment and bone resorption in the murine calvarial model. CONCLUSION: These results suggest that berberine may have therapeutic effect for osteolysis induced by wear particles and LPS in gram-negative bacteria.

Copper and silver ion implantation of aluminium oxide-blasted titanium surfaces: proliferative response of osteoblasts and antibacterial effects.

Implant infection still represents a major clinical problem in orthopedic surgery. We therefore tested the in vitro biocompatibility and antibacterial effects of copper (Cu)- and silver (Ag)-ion implantation. Discs of a commonly used titanium alloy (Ti6AlV4) with an aluminium oxide-blasted surface were treated by Cu- or Ag-ion implantation with different dosage regimen (ranging from 1e15-17 ions cm(-2) at energies of 2-20 keV). The samples were seeded with primary human osteoblasts and cell attachment and proliferation was analyzed by an MTT-assay. In comparison to the reference titanium alloy there was no difference in the number of attached viable cells after two days. After seven days the number of viable cells was increased for Cu with 1e17 ions cm(-2) at 2 and 5 keV, and for Ag with 1e16 ions cm(-2) at 5 keV while it was reduced for the highest amount of Ag deposition (1e17 ions cm(-2) at 20 keV). Antibacterial effects on S.aureus and E.coli were marginal for the studied dosages of Cu but clearly present for Ag with 1e16 ions cm(-2) at 2 and 5 keV and 1e17 ions cm(-2) at 20 keV. These results indicate that Ag-ion implantation may be a promising methodological approach for antibacterial functionalization of titanium implants.

Strategies to reduce blood loss in lower extremity total joint arthroplasty.

Concerns about blood loss and the safety of allogenic blood transfusion have led to the development of many transfusion options for lower extremity joint arthroplasty. Techniques for dealing with such blood loss include allogenic blood transfusion, autologous donation and transfusion, hemodilution, perioperative blood salvage, intraoperative cell savers, bipolar sealers, and pharmacological agents. A blood management strategy must consider both the patient and the surgical procedure, assess the transfusion risks, and formulate a plan to address them appropriately. This article is an overview of the blood management techniques for lower extremity joint arthroplasty. The purpose of this review is to report our opinion regarding the use of alternative blood management strategies and to discuss the possible advantages and disadvantages of each technique. The results of this review indicate that a patient-focused algorithm using one or more strategies such as preoperative administration of erythropoietin, preoperative autologous blood donation, use of a bipolar sealer, intraoperative blood collection and reinfusion, as well as postoperative reinfusion drains may reduce the need for allogenic blood transfusions in patients undergoing primary and revision lower-extremity joint arthroplasties. The authors believe that a patient-specific algorithm utilizing the aforementioned techniques can lead to a substantial decrease in morbidity and mortality and an overall cost saving for both patients and medical institutions.

The influence of orthopaedic implants on patient tolerance of neuromuscular electrical stimulation (NMES).

Neuromuscular electrical stimulation (NMES) is a potential deep vein thrombosis (DVT) preventative measure that is often over-looked. NMES could be used postoperatively in conjunction with pharmacological prophylaxis to further reduce the incidence rate of DVT following orthopaedic surgery. However, the use of NMES in the recovery period following orthopaedic surgery on patients with metallic hip/knee implants has not been tested to date. The presence of a metallic implant may interfere with the NMES generated electric field causing hypersensitivity at the implant site. This may essentially limit the use of NMES postoperatively. Consequently, patient tolerance of NMES must be assessed before any treatment can be administered. Five hip replacement patients and 5 knee replacement patients participated in this study that were at least 3 weeks post-op. NMES was applied to the calf muscles of each patient using skin surface electrodes and the stimulation intensity was slowly increased. Comfort was assessed by asking the patient to indicate the stimulation intensity corresponding to 4 thresholds: when they first felt the stimulus sensation (sensory threshold), when a muscle contraction was observed (motor threshold), when stimulation became uncomfortable (pain threshold) and when the stimulation became unbearable (pain tolerance). Patients also indicated their overall comfort level on a visual analogue scale and completed a short verbal interview detailing their experience of the NMES treatment. Results indicated that the presence of a metallic implant did not give rise to hypersensitivity to NMES. Patients found the application of calf muscle NMES comfortable and acceptable as a treatment. We conclude that use of NMES on postoperative orthopaedic patients can be safely considered as a DVT prevention method.

Guiding empirical antibiotic therapy in orthopaedics: The microbiology of prosthetic joint infection managed by debridement, irrigation and prosthesis retention.

OBJECTIVES: This study describes the microbiological spectrum of prosthetic joint infection (PJI) managed by debridement, washout and retention and so guides the choice of empirical antibiotics within this patient group. METHODS: We performed a retrospective review of all patients admitted to our specialist tertiary unit for PJI who were managed with debridement and irrigation or arthroscopic washout of infected prosthetic joints between 1st January 1998 and 30th April 2003. Clinical and microbiological data sets were analysed using the Access database. RESULTS: One hundred and twelve patients met the criteria for inclusion. 69% received their surgical intervention in the first three months after implantation ('early') and 21% after 12 months. Overall the most frequently isolated organisms were coagulase negative staphylococci (47% patients) and methicillin-sensitive Staphylococcus aureus (MSSA, 44% patients). 8% grew methicillin-resistant Staphylococcus aureus (MRSA) and 7% grew anaerobes. Most Gram-negative isolates were resistant to cefuroxime; all were sensitive to meropenem. Eighty-six percent of polymicrobial cultures occurred in early infections when 47% of patients grew more than one organism. MSSA was the most frequently isolated organism at all time points. CONCLUSIONS: Most infections involved staphylococci. MRSA was infrequently isolated. Most polymicrobial infections occurred in early infection. A high rate of resistance to cephalosporins among Gram-negative organisms justifies the use of a broader agent such as a carbapenem in the early empirical antibiotic regime for PJI.

A patient with MRSA infection to prosthesis of femoral head diagnosed non-invasively using bi-digital O-ring test: a clinical case report.

Prosthesis of femoral head is a common surgical procedure, but the diagnosis of infection associated with the prosthesis remains difficult. We diagnosed non-invasively methicillin resistant Staphylococcus aureus (MRSA) infection of prosthesis of femoral head with Bi-Digital O-Ring Test (BDORT). BDORT uses the resonance phenomenon between 2 identical substances, and electromagnetic field principle. The method can non-invasively detect viral & bacterial infection. Accuracy of the BDORT findings was confirmed through bacterial culture & sensitivity test to antibiotics. Patient was successfully treated with operation of evulsion of the prosthesis of femoral head and administration of antibiotics and Cilantro. The drug compatibility was tested with BDORT. BDORT was an effective technique for non-invasively detecting infection of prosthesis and selecting the most effective antibiotics.

[Total inverted shoulder prosthesis and rotator cuff insufficiency: evaluation and determination of anatomical parameters predictive of good functional outcome in 21 shoulders]. / Prothèse totale inversée de l'épaule et insuffisance de la coiffe des rotateurs: évaluation et approche de paramètres anatomiques prédictifs d'une bonne fonctionnalité à propos de 21 cas.

OBJECTIVE: Evaluation of the functional results of the Delta 3 inverted shoulder prosthesis and determination of a radio-anatomical index predictive of best functional outcome. PATIENTS AND METHODS: Retrospective analysis of 19 patients (21 shoulders). Clinical (pain, satisfaction, amplitudes, Constant index) and radiological (acromio-epiphyseal distance) evaluation at a mean follow up of 13.6 months. RESULTS: Outcomes concerning pain, quality of life and Constant index were good and similar to other series. Few complications were observed. An increase of the acromio-epiphyseal distance of 33 to 50% compared to the non operated side is associated with a good functional result. CONCLUSION: Our results confirm those of other series and show that Delta 3 inverted prosthesis is an efficient therapeutic alternative in arthropathy with rotator cuff tears. Rehabilitation is fairly short and easy. The increase of the acromio-epiphyseal distance determines the tension of the deltoid muscle and could predict a favorable outcome.

Alendronate did not inhibit instability-induced bone resorption. A study in rats.

Alendronate is a bisphosphonate that can decrease osteoclastic activity. It has been suggested as treatment for periprosthetic osteolysis. We used 48 rats, of which 32 had a plate implant on one tibia, to study the effect of alendronate on bone resorption at an unstable implant-bone interface. The plate has a handle on top, which can be grasped through the skin and turned, to create a sliding motion of a titanium surface against the underlying bone. This is known to result in bone resorption, which was studied by histomorphometry. Osmotic minipumps were used to administer alendronate at 0.063 mg/kg/day or saline. The systemic effect of the treatment was assessed by ashing the proximal metaphyses of the tibia of the contralateral unoperated leg. The ash-weight was increased in the alendronate-treated group by 43% (p = 0.0001), corresponding to histological changes in the metaphyseal bone. There was no inhibition of the instability-induced bone resorption at the test surface by alendronate: bone was being resorbed and replaced by a tissue similar to a loosening membrane.

Oligoclonal T-cell proliferation and interferon-gamma production in periprosthetic inflammation.

Total joint arthroplasty has dramatically changed the treatment options for patients with destructive joint disease. The materials used to manufacture implants are regarded as biologically inert; accordingly, arthroplasty is a very successful intervention for most patients. However, a subset of patients develops an inflammatory reaction around the prosthesis, causing implant loosening and irreversible bone destruction. To identify mechanisms leading to periprosthetic inflammation, the function and composition of macrophages and T cells accumulated in the pseudosynovia were examined. Tissue-infiltrating macrophages synthesized a spectrum of proinflammatory cytokines including IL-1beta, IL-6, and TGF-beta. T cells recruited to the periprosthetic inflammatory lesions were characterized by restricted diversity of T-cell receptors and the emergence of dominant clonal populations. T cells with identical T-cell receptor sequences, and thus with identical antigen specificity, were isolated from anatomically distinct and independent regions of the tissue. Transcription of IL-2, IFN-gamma, and, in some patients, IL-4 genes in the periprosthetic membrane indicated functional activation of infiltrating T cells. Correlation of periprosthetic osteolysis with the tissue cytokine pattern demonstrated a relationship between IFN-gamma transcription and bone loss. We propose that antigen-recognition events are critically involved in the development of periprosthetic inflammation and that the functional commitment of T cells recruited to the periprosthetic region influences whether periprosthetic inflammation is complicated by bone destruction.