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Background Ulnar collateral ligament reconstruction (UCLR) is the gold standard for treating ulnar collateral ligament injuries in throwing athletes who have failed conservative treatment. There are several described techniques that produce successful and reproducible outcomes. In addition, there is biomechanical evidence that supports hybrid fixation of the graft with a docking technique on the humeral side and suspensory fixation on the ulnar side. However, as of this writing there are no clinical studies that have reported results. This retrospective case series is the first of its kind to report on clinical outcomes following UCLR with hybrid suspensory fixation. Methods Fifty throwing athletes who underwent ULCR with hybrid suspensory fixation from 2010-2017 by one of 5 surgeons at a single institution were available at a median follow-up of 7 years. Return to sport, level of sport, and postoperative complications were recorded at final follow-up. Results A total of 50 patients were included in final analysis. Nearly all were able to return to sport at the same level or higher (48/50, 96%). One of these 50 athletes (2%) played professionally, 27 (54%) played collegiately, and 21 (42%) played at the high school level. Seven patients (14%) underwent reoperation following the index procedure. The median (interquartile range) Quick Disabilities of the Arm, Shoulder, and Hand questionnaire score was 0.098 (0-4.5) at final follow-up. Conclusion Hybrid suspensory fixation is a safe and effective technique for UCLR in the throwing athlete. Throwers can expect to return to sport at a very high rate with low risks for postoperative complications.

BACKGROUND As the numbers of senior golfers increase, many will consider a hip or knee joint replacement (JR) over their lifetime. The relationship of JR to the rate of return and validated level of play has not been well defined. METHODS A regional golf association's membership was mailed a questionnaire regarding their JR. Members with valid Golf Handicap Information Network numbers and with at least five pre- and post-JR scores were included. Prospectively collected rounds of play and handicap differentials were used for the analysis. RESULTS Two hundred fifty-one members reported having a JR, with 120 qualifying for the analysis. The sites of JR include 50 hips (41.7%) and 70 kness (58.3%). Plays per month after the first JR increased from 5.2 to 5.6 (P = 0.017). Handicap differentials increased from an average of 15.8 to 17.3 (P < 0.0001). Average return to play was 62 days. Twenty-eight players who had a second JR saw an increase in plays per month from 4.2 to 6.3 (P = 0.0074) and an increase in handicap differentials from 19.3 to 20.2 (P = 0.0036). CONCLUSIONS After the initial JR, amateur golfers will likely play more frequently; however, the level of play will typically decrease slightly. The same effects are seen after a subsequent JR. LEVEL OF EVIDENCE Level IV: retrospective, cross-sectional review.

Background Although ulnar neuritis can occur secondary to ulnar collateral ligament pathology, stress fractures, and traction apophysitis, isolated ulnar nerve dysfunction can lead to medial elbow pain. The purpose of this study was to evaluate the short-term outcomes of overhead athletes undergoing anterior ulnar nerve transposition for ulnar neuropathy. Methods All overhead athletes who underwent isolated ulnar nerve transposition between 2009 and 2016 for refractory ulnar neuritis were identified. The primary outcome was return to sport, and secondary outcome measures included the Kerlan-Jobe Orthopaedic Clinic score; Mayo Elbow Performance Score; Quick Disabilities of the Arm, Shoulder and Hand score; Single Assessment Numeric Evaluation score; and visual analog scale score for pain. Complication and reoperation rates were recorded. Results A total of 26 overhead athletes (21 male and 5 female athletes) underwent ulnar nerve transposition at an average age of 18.4 years (range, 11-25 years). Of the patients, 24 (92%) returned to their sporting activity at an average of 2.7 months postoperatively, including 16 (62%) at the previous level of play. The average visual analog scale pain score improved from 4.7 (±2.5) to 0.4 (±1.5) (P = .015). The average postoperative patient-reported outcome scores were as follows: Kerlan-Jobe Orthopaedic Clinic score, 80 (95% confidence interval [CI], 72.7-87.0); Single Assessment Numeric Evaluation score, 85 (95% CI, 75.4-94.7); Quick Disabilities of the Arm, Shoulder and Hand score, 5 (95% CI, 2.1-7.7); and Mayo Elbow Performance Score, 91 (95% CI, 86.8-96.0). Conclusion Cubital tunnel syndrome can cause medial elbow pain in overhead athletes in the presence of a normal ulnar collateral ligament. At mid-term follow-up, 92% of overhead athletes returned to sport after ulnar nerve transposition, with 62% resuming their previous level of performance.

The utility of next-generation sequencing (NGS) in differentiating between active infection and contaminant or baseline flora remains unclear. The purpose of this study is to compare NGS with culture-based methods in primary shoulder arthroplasty.A prospective series of primary shoulder arthroplasty patients with no history of infection or antibiotic use within 60 days of surgery was enrolled. All patients received standard perioperative antibiotics. After skin incision, a 10 × 3-mm sample of the medial skin edge was excised. A 2 × 2-cm synovial tissue biopsy was taken from the rotator interval after subscapularis takedown. Each sample set was halved and sent for NGS and standard cultures.Samples from 25 patients were analyzed. Standard aerobic/anaerobic cultures were positive in 10 skin samples (40%, 95% confidence interval [CI] 20%-60%) and 3 deep tissue samples (12%, 90% CI 1%-23%]). NGS detected ≥1 bacterial species in 17 of the skin samples (68%, 95% CI 49%-87%) and 7 deep tissue samples (28%, 95% CI 9%-47%). There was a significant difference (P.03) in the mean number of bacterial species detected with NGS between the positive standard culture (1.6 species) and the negative standard culture groups (5.7 species).NGS identified bacteria at higher rates in skin and deep tissue samples than standard culture did in native, uninfected patients undergoing primary procedures. Further research is needed to determine which NGS results are clinically relevant and which are false positives before NGS can be reliably used in orthopedic cases.

To compare subjective and objective outcomes of fibular and combined tibial-fibular (TF)-based posterolateral corner (PLC) reconstruction.A systematic review of literature reporting outcomes of posterolateral corner reconstruction was conducted including outcome studies of surgically treated PLC injuries with a minimum 1-year follow-up, postoperative subjective and objective outcomes including the patient-reported outcome scorings of Lysholm score, International Knee Documentation Committee evaluation (subjective and objective), dial test, and varus stress radiographs.The 32 studies included comprised 40 cohorts: 12 cohorts (n = 350 knees) used a fibular-based technique, and 28 cohorts (n = 593 knees) used a combined TF-based technique. No statistically significant differences were found in patient-reported outcomes or objective clinical measurements comparing the two techniques using the Lysholm score (P = 0.204, τ2 = 3.46), International Knee Documentation Committee evaluation (subjective P = 0.21 τ2 = 15.57; objective P = 0.398), dial test (P = 0.69), or varus stress radiographs (P = 0.98, τ2 = 0.08).This study found no statistically significant differences in subjective or objective clinical outcome measurements after fibular-based versus combined TF-based PLC reconstruction. Further prospective evaluation comparing long-term clinical outcomes, complications, and surgical time may help to elucidate a preferred reconstructive technique.

Background Postoperative infection after shoulder arthroplasty is a devastating complication. Multiple patient risk factors have been associated with postoperative infection, including increased body mass index and diabetes. Although the association between preoperative glucose control and infection has been established, little is known about the effect of perioperative glycemic control on outcomes following shoulder arthroplasty. The purpose of this study was to investigate the association between postoperative glycemic variability and short-term complications after total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA). Methods A retrospective study was performed at a large, single-specialty center from January 2015 to December 2018. Patients were included if they underwent primary TSA or RTSA with a minimum of 90 days' follow-up and had a minimum of 1 serum glucose value obtained per day of the hospital stay or had ≥3 measurements obtained during the hospital admission period. The primary outcome variable was postoperative infection per accepted definitions of surgical-site infection or periprosthetic joint infection. Secondary outcome variables included stiffness, periprosthetic fracture, periprosthetic dislocation, and reoperation. Results In total, 1074 TSAs or RTSAs (in 1032 patients) met the eligibility criteria. The mean patient age was 69.9 ± 8.4 years, and 40.3% of patients had a preoperative diagnosis of diabetes mellitus. Of the patients, 670 (62%) had a calculable coefficient of variation. A younger patient age (median, 65 years [interquartile range (IQR), 13.5 years] vs. 71 years [IQR, 11.0 years]; P = .02) and a preoperative diagnosis of diabetes mellitus (P = .01) showed statistically significant associations with postoperative infection. The first in-hospital glucose measurement beyond the reference tertile of 70-140 mg/dL showed a statistically significant association with postoperative infection, with a median of 128.0 mg/dL (IQR, 43 mg/dL) vs. 167.5 mg/dL (IQR, 37.0 mg/dL; P = .01), whereas the second and third glucose measurements showed no association with postoperative infection. We found no associations between the coefficient of variation and reoperations or complications including surgical-site infection, periprosthetic joint infection, death, postoperative infection, periprosthetic fracture, or stiffness. Conclusion We found an association between a preoperative diagnosis of diabetes mellitus and postoperative infection following shoulder arthroplasty. We also found that an elevated first glucose measurement is associated with the development of postoperative infection. In-hospital glycemic control, as well as preoperative glycemic control and optimization, may be beneficial for reducing postoperative infections following shoulder arthroplasty.

Purpose To evaluate the tibiofemoral contact mechanics of an all-inside posterior medial meniscal root repair technique via suture fixation to the posterior cruciate ligament (PCL) and to compare with that of the intact knee and the knee with a root tear. Methods Tibiofemoral contact mechanics were recorded in 8 human cadaveric knee specimens using pressure sensors. Each knee underwent 3 testing conditions related to the posterior medial meniscal root: (1) intact knee; (2) root tear; and (3) all-inside repair via suture fixation to the PCL. Knees were loaded with a 1000-N axial compressive force at 4 knee flexion angles (0°, 30°, 60°, 90°). Calculations were performed for contact area, mean contact pressure, and peak contact pressure. A generalized linear model with a Tukey adjusted least square means test was used to determine differences between testing conditions. Results Across all knee flexion angles, there was an overall mean 26.3% reduction in contact area with root tear (211.34 mm2 vs intact 286.64 mm2, P = .0002), and a 31.6% increase from root tear to repair (277.61 mm2, P = .0297). Across all knee flexion angles, there was an overall mean 24.3% increase in contact pressure with root tear (1849.12 N/mm2 vs. intact 1487.52 N/mm2, P Conclusions In most testing conditions and with overall averaging across knee flexion angles, the all-inside posterior medial meniscal root repair with suture fixation to the adjacent PCL fibers restored contact area (from 26.3% reduction with root tear to 31.6% increase with repair), contact pressures (from 24.3% increase with root tear to 31.1% decrease with repair), and peak contact pressures (from 10.6% increase with root tear to 12.4% decrease with repair) to that of the intact knee This may be a future potential technique to limit complications associated with the traditional transtibial pull-out method of repair. Clinical Relevance This technique may provide a posterior medial meniscal root repair construct that restores most tibiofemoral contact mechanics and offers theoretical benefits of technical ease and potential for an acceptable, less “anatomic” repair location.

Purpose To examine allograft augmentation of undersized hamstring (HS) autograft tendons at the time of anterior cruciate ligament (ACL) reconstruction, compared with un-augmented autograft HS ACL reconstruction. Methods Patients who underwent ACL reconstruction at our institution between 2005 and 2015 were reviewed. Inclusion criteria included patients who underwent (1) primary ACL reconstruction, (2) use of a hybrid HS autograft with allograft augmentation, and (3) had a minimum 2-year postoperative follow-up. Patients with revision ACL, multiligamentous injuries, all-epiphyseal fixation techniques, or additional procedures beyond chondroplasty or meniscal repair/debridement were excluded. Data collected included demographics, graft size, concomitant procedures, revision operation, revision ACL reconstruction, and patient-reported outcomes. Results In total, 59 patients met criteria for inclusion into the hybrid group, and 80 patients were eligible for inclusion into the control group. The average age of the cohort was 22.9 (interquartile range Q1:17, Q3: 38.3), and 51.8% of the patients were female. Seven patients (11.9%) in the hybrid ACL group underwent revision ACL surgery versus 15 (18.8%) in the control group (P = .27). There was no difference in patient-reported outcomes between groups. Conclusions Augmenting an HS ACL autograft that is 8 mm or less with allograft tissue to increase the overall size of the ACL graft shows no difference in overall reoperation or revision of ACL failure. The hybrid autograft/allograft ACL reconstruction patients showed no clinically important difference between groups in patient-reported outcome measures. Level of Evidence Level III, case–control comparative analysis.

Background Total knee arthroplasty is a successful operation for treatment of arthritis. However, devastating wound complications and infections can compromise the knee joint, particularly in revision situations. Methods Soft tissue loss associated with poor wound healing and multiple operations can necessitate the need for reconstruction for wound closure and protection of the prosthesis. Results Coverage options range from simple closure methods to complex reconstruction, including delayed primary closure, healing by secondary intention, vacuum-assisted closure, skin grafting, local flap coverage, and distant microsurgical tissue transfer. Conclusion Understanding the advantages and pitfalls of each reconstructive option helps to guide treatment and avoid repeated operations and potentially devastating consequences such as knee arthrodesis or amputation.

Background Chronic elbow instability after trauma is a challenging problem. Clinical results of external elbow fixation in this setting are limited, with most studies focusing on hinged external fixation. A static fixator is an alternative for maintaining joint reduction. Advantages of a static frame include ease of application, decreased need for special instrumentation, and more secure maintenance of a concentrically reduced joint in the setting of bone or soft tissue instability. The primary limitation of static fixation is the potential for stiffness. Methods This retrospective review represents the largest reported cohort evaluating the use of static elbow external fixation for the treatment of chronic elbow instability. Twenty-seven cases treated by a single surgeon between 2004 and 2015 were identified. Results Twenty patients were available for a clinical evaluation, including radiographs and a physical examination at a mean follow-up of 5.8 years (range, 1.4-12.4 years). Of note, 19 of 20 were clinically obese or overweight. At final evaluation, range of motion averaged from 20° ± 13° of extension to 134° ± 9° of flexion. All patients had stable elbows, except 1 patient who had valgus and varus laxity on stress examination. Radiographs of this patient showed an incongruous joint. Eight patients required an additional operation after external fixator removal, 3 for infection and 5 for stiffness. Conclusions At almost 6 years of follow-up, static elbow external fixator resulted in a congruous joint with adequate functional and clinical outcomes in 95% of patients.

Propionibacterium acnes (P. acnes) is the most common bacteria associated with infection after shoulder arthroplasty. These bacteria can be grown on culture of skin after standard preoperative skin preparation and antibiotics. The purpose of this study was to determine whether adding preoperative intravenous doxycycline reduces the prevalence of positive P. acnes cultures of skin and deep tissues at the time of prosthetic joint implantation during shoulder arthroplasty.This was a randomized controlled trial. An a priori power analysis determined that a sample size of 56 patients was necessary. Patients scheduled to undergo shoulder arthroplasty were randomized to receive either standard perioperative cefazolin or a combination of doxycycline and cefazolin. Tissue specimens for culture were then taken from the skin edge, and swabs of the superficial dermal tissue and glenohumeral joint were obtained. All cultures were maintained for 14 days to allow for P. acnes detection. Groups were compared to determine if the addition of doxycycline reduced the rate of culture positivity.Fifty-six patients were enrolled and randomized. Twenty-one (38%) had ≥1 positive cultures for P. acnes, with no significant difference between the group treated with cefazolin alone (10 [37%] of 27 patients) and the combined doxycycline and cefazolin group (11 [38%] of 29 patients) (p = 0.99). The greatest numbers of culture-positive samples were obtained from the skin (30%), followed by dermal tissue (20%) and the glenohumeral joint (5%). Patients who had ≥1 positive cultures were younger than those who did not (mean age [and standard deviation], 64.9 ± 7.7 versus 69.4 ± 7.7 years; p = 0.041), had a greater tendency to be male (16 [76%] of 21 versus 17 [49%] of 35; p = 0.053), and had a lower Charlson Comorbidity Index (3.35 ± 1.3 versus 4.09 ± 1.4; p = 0.051). There were no significant differences between the culture-positive and culture-negative groups in terms of body mass index (BMI) (p = 0.446) or arthroplasty type, with positive cultures found for 8 of the 29 anatomic shoulder arthroplasty procedures compared with 13 of the 27 reverse shoulder arthroplasty procedures (p = 0.280). There were no doxycycline-related adverse events.In this randomized controlled trial, doxycycline did not significantly decrease P. acnes culture positivity of the skin, dermis, or glenohumeral joint of patients undergoing shoulder arthroplasty. The addition of prophylactic intravenous antibiotics to cover P. acnes may not be an effective method to reduce postoperative and periprosthetic shoulder joint infections.Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background: The Internet is a widely used resource by patients however, objective data on details such as frequency of usage and specific sites visited is lacking. We surveyed patients from hand surgery practices to describe patient preferences and utilization patterns for online resources. Methods: From October 2015 to June 2016, we enrolled patients presenting to 4 orthopedic hand surgeons at 2 academic institutions. Patients completed a survey, with questions related to their preference for learning about their diagnosis and Internet utilization both before and after the visit. Results: A total of 226 patients were enrolled in the study. Forty-five percent of the patients had done online research prior to the office visit, and 81% preferred to learn about their diagnosis through verbal communication, as opposed to only 8% who listed Web site information. Fifty percent indicated that there was a greater than 50% chance or they would definitely seek additional information on the Internet after the office visit. When asked to choose from a list of Web sites to visit, the most popular Web site was WebMD. Specialty society Web sites (American Society for Surgery of the Hand and American Academy of Orthopaedic Surgeons) were less popular. Conclusions: This survey-based study found that a majority of patients utilize the Internet both before and after the office visit; however, they often utilize unregulated sites for information. This information can help physicians guide patients to high-quality Web sites for information on their clinical diagnosis and treatment.

Evaluation of the fractured pelvis or acetabulum requires both standard radiographic evaluation as well as computed tomography (CT) imaging. The standard anterior-posterior (AP), Judet, and inlet and outlet views can now be simulated using data acquired during CT, decreasing patient discomfort, radiation exposure, and cost to the healthcare system. The purpose of this study is to compare the image quality of conventional radiographic views of the traumatized pelvis to virtual radiographs created from pelvic CT scans. Five patients with acetabular fractures and ten patients with pelvic ring injuries were identified using the orthopedic trauma database at our institution. These fractures were evaluated with both conventional radiographs as well as virtual radiographs generated from a CT scan. A web-based survey was created to query overall image quality and visibility of relevant anatomic structures. This survey was then administered to members of the Orthopaedic Trauma Association (OTA). Ninety-seven surgeons completed the acetabular fracture survey and 87 completed the pelvic fracture survey. Overall image quality was judged to be statistically superior for the virtual as compared to conventional images for acetabular fractures (3.15 vs. 2.98, p = 0.02), as well as pelvic ring injuries (2.21 vs. 1.45, p = 0.0001). Visibility ratings for each anatomic landmark were statistically superior with virtual images as well. Virtual radiographs of pelvic and acetabular fractures offer superior image quality, improved comfort, decreased radiation exposure, and a more cost-effective alternative to conventional radiographs.

We present 20 patients with established proximal pole scaphoid nonunions treated with curettage and cancellous autograft from the distal radius and screw fixation. Fractures with significant proximal pole fragmentation were excluded. Patients were treated at a mean of 26 weeks after injury (range 12–72). Union occurred in 18 of 20 patients (90%) based on computed tomographic imaging. The two nonunions that did not heal were treated with repeat curettage and debridement and iliac crest bone grafting without revision of fixation. Union was achieved in both at a mean of 11 weeks after the revision procedures. Our findings suggest that non-vascularized cancellous autograft and antegrade fixation is a useful option for the treatment of proximal pole scaphoid nonunions.Level of evidence: IV

Background: An intra-articular injection of local anesthetics is a common procedure for diagnostic and therapeutic purposes. It has been shown that these agents are toxic to articular cartilage and synovial tissue in a dose- and time-dependent fashion, and in some cases, they may lead to postarthroscopic glenohumeral chondrolysis (PAGCL). However, the role of apoptosis in cell death is still unclear, and the potential role of apoptosis inhibition in minimizing chondrocyte and synovial cell death has not been reported. Purpose: (1) To quantify the degree of apoptotic cell death in chondrocytes and synovial cells exposed to local anesthetics, and (2) to determine whether caspase inhibition could reduce cell death. Study Design: Controlled laboratory study. Methods: Human chondrocytes and synovial cells were expanded in vitro and exposed to normal saline, 0.5% bupivacaine, 0.5% ropivacaine, 1% lidocaine, or 1:1000 epinephrine for 90 minutes. Apoptosis was then detected at 1, 3, 5, and 7 days after exposure using terminal deoxynucleotidyl transferase (TdT)–mediated dUTP nick-end labeling (TUNEL) and immunohistochemistry. Apoptosis was then inhibited using the pan-caspase inhibitor z-vad- fmk. Results were normalized to normal saline controls and analyzed by generalized regression models and pairwise confidence intervals. Results: Analysis of cumulative chondrocyte apoptosis relative to controls after anesthetic exposure demonstrated more than 60% cell death with 0.5% bupivacaine and 1:1000 epinephrine. The greatest chondroprotective effect of caspase inhibition occurred with 0.5% ropivacaine. Similarly, in synovial cells, epinephrine was also very cytotoxic; however, 1% lidocaine induced the most apoptosis. Synovial cells exposed to 0.5% ropivacaine were again most sensitive to protective caspase inhibition. Conclusion: Local anesthetics induce chondrocyte and synovial cell apoptosis in a time-dependent fashion, with peak apoptosis occurring 5 days after exposure. Both chondrocytes and synovial cells are most sensitive to caspase inhibition after exposure to 0.5% ropivacaine. Clinical Relevance: Apoptosis inhibition may be an effective strategy in minimizing chondrocyte and synovial cell death after exposure to anesthetics. Further investigation is clinically warranted.

Total shoulder arthroplasty (TSA) in cases with posterior wear can be addressed by eccentric reaming of the anterior glenoid or by augmenting the posterior glenoid with bone grafting or augmented glenoid implants. We report the results of TSA with posterior glenoid bone grafting (PGBG) with humeral head autograft in patients with shoulder osteoarthritis and severe posterior glenoid wear.A retrospective review of cases from 2004 to 2014 revealed 34 patients. Preoperative and postoperative radiographs were evaluated for glenoid version and humeral head subluxation as well as component loosening. Patient-reported outcomes were compared preoperatively and postoperatively. Complications and reoperations were also evaluated.Of the 34 patients, 28 (82.4%) were available at a minimum of 2 years' follow-up. PGBG corrected glenoid retroversion from -28° ± 4° preoperatively to -4° ± 2° (P .001). Humeral head subluxation also improved after PGBG with respect to the scapular axis and to the midglenoid face (P .001). Radiographic analysis revealed all PGBGs had incorporated. Radiographically, 3 patients (10.7%) had a total of 5 broken or displaced screws. In addition, 3 patients (10.7%) had a broken metal marker in the center peg of the glenoid component. No patients required component revision surgery by final follow-up. Only 1 reoperation occurred for capsular release. Patients showed significant improvements in all patient-reported outcomes.Patients undergoing primary TSA with humeral head autograft PGBG showed significant improvements in glenoid version, humeral head subluxation, patient-reported outcomes, and range of motion at an average of 4 years' follow-up. There was a low revision rate and a high rate of graft incorporation.

Background New medical doctors enter their residency fields in July, a time in the hospital in which patient morbidity and mortality rates are perceived to be higher. It remains controversial whether a “July effect” exists in different areas of medicine and surgery, including in orthopedic surgery. The purpose of this study is to test for the July effect in patients undergoing primary total shoulder arthroplasty (TSA). Methods Patients who underwent primary TSA from 2005-2012 were identified using the American College of Surgeons National Surgical Quality Improvement Program database. Cases were categorized as involving residents or fellows and as occurring during the first academic quarter. Rates of composite and any adverse event outcomes were compared between patient groups using multivariate logistic regression. Results A total of 1591 patients met the inclusion criteria. Of these cases, 711 (44.7%) had resident or fellow involvement and 390 (24.5%) were performed in the first academic quarter. There were few demographic and comorbidity differences between cases with and without residents or fellows or between cases performed during the first quarter and during the rest of the year. Overall, the rate of serious adverse events was 1.6% and the rate of any adverse events was 6.5%. Discussion and conclusion Using one of the largest cohorts of primary TSA patients, this study could not provide evidence for a July effect. In the context of the recent growth in the volume of TSA procedures, these findings provide important reassurance to patients that it is safe to schedule their elective procedures at training institutions during the first part of the academic year.

Treatment of critical size bone defects is challenging. Recent studies showed that the cytokine stromal cell-derived factor 1 alpha (SDF-1α) has potential to improve the bone regenerative effect of low bone morphogenetic protein 2 (BMP-2) concentrations. The goal of this study was to demonstrate the combined effect of SDF-1α and BMP-2 on bone regeneration and stem cell recruitment using a critical size femoral bone defect model. A total of 72 mice were randomized to six groups. External fixators were implanted onto the right femur of each mouse and 3 mm defects were created. Depending on the group affiliation, adenovirally activated fat tissue grafts expressing SDF-1α or/and BMP-2 were implanted at the defect site. One day after operation, 1×106 murine mesenchymal stromal cells (MSCs), lentivirally transduced to express the gene enhanced green fluorescent protein (eGFP), firefly luciferase, and CXCR4 were injected systemically in selected groups. Migration of the injected MSCs was observed by bioluminescence imaging on days 0, 2, 4, 6, 8, 10, 12, 14, 21, 28, and 42. After 6 weeks, animals were euthanized and 80 μm CT-scans were performed. For histological investigations, hematoxylin and eosin-, tartrate-resistant acid phosphatase-, alkaline phosphatase-, and anti-eGFP-stained sections were prepared. BMP-2 and SDF-1α combined at the defect site increased bone volume (BV) (2.72 mm3; 95% CI 1.95–3.49 mm3) compared with the negative control group (1.80 mm3; 95% CI 1.56–2.04 mm3; p

The generation of wear debris is an inevitable result of normal usage of joint replacements. Wear debris particles stimulate local and systemic biological reactions resulting in chronic inflammation, periprosthetic bone destruction, and eventually, implant loosening and revision surgery. The latter may be indicated in up to 15% patients in the decade following the arthroplasty using conventional polyethylene. Macrophages play multiple roles in both inflammation and in maintaining tissue homeostasis. As sentinels of the innate immune system, they are central to the initiation of this inflammatory cascade, characterized by the release of pro-inflammatory and pro-osteoclastic factors. Similar to the response to pathogens, wear particles elicit a macrophage response, based on the unique properties of the cells belonging to this lineage, including sensing, chemotaxis, phagocytosis, and adaptive stimulation. The biological processes involved are complex, redundant, both local and systemic, and highly adaptive. Cells of the monocyte/macrophage lineage are implicated in this phenomenon, ultimately resulting in differentiation and activation of bone resorbing osteoclasts. Simultaneously, other distinct macrophage populations inhibit inflammation and protect the bone-implant interface from osteolysis. Here, the current knowledge about the physiology of monocyte/macrophage lineage cells is reviewed. In addition, the pattern and consequences of their interaction with wear debris and the recent developments in this field are presented.

Currently, younger, more active patients are being offered total joint replacement (TJR) for end-stage arthritic disorders. Despite improved durability of TJRs, particle-associated wear of the bearing surfaces continues to be associated with particulate debris, which can activate monocyte/macrophages. Activated macrophages then produce pro-inflammatory factors and cytokines that induce an inflammatory reaction that activates osteoclasts leading to bone breakdown and aseptic loosening. We hypothesized that activated macrophages in tissues harvested from revised joint replacements predominantly express an M1 pro-inflammatory phenotype due to wear-particle-associated cell activation, rather than an M2 anti-inflammatory phenotype. We further questioned whether it is possible to convert uncommitted monocyte/macrophages to an M2 phenotype by the addition of interleukin-4 (IL-4), or whether it is necessary to first pass through an M1 intermediate stage. Retrieved periprosthetic tissues demonstrated increased M1/M2 macrophage ratios compared to non-operated osteoarthritic synovial tissues, using immunohistochemical staining and Western blotting. Uncommitted monocyte/macrophages with/without polymethyl-methacrylate particles were transformed to an M2 phenotype by IL-4 more efficiently when the cells were first passed through an M1 phenotype by exposure to endotoxin. Wear particles induce a pro-inflammatory microenvironment that facilitates osteolysis; these events may potentially be modulated favorably by exposure to IL-4.