What Is the Correlation between Coronal Plane Alignment Measured on Pre- and Postoperative Weight-bearing Radiographs and Intraoperative Navigation When Stress Is Applied to the Knee?

This study examines the correlation between the weight-bearing (WB) long leg radiograph (LLR)-derived hip-knee-ankle angle (HKAA) and intraoperative supine computer-assisted surgery (CAS)-derived HKAA measurements at the beginning and end of total knee arthroplasty (TKA). The primary aim of the study was to determine if WB alignment could be mimicked or inferred based on intraoperative alignment findings. We conducted a prospective analysis from a cohort of 129 TKAs undergoing a CAS TKA at a single center by a single surgeon. The HKAA was recorded using the CAS navigation system immediately postregistration of navigation data and after implantation of the prosthesis. The intraoperative HKAA was recorded in both the supine "resting" position of the knee and also while the knee was manipulated in an effort to replicate the patient's WB alignment. These measurements were compared with the HKAA recorded on pre- and postoperative WB LLRs. There was a strong correlation between the preoperative WB LLR HKAA and the intraoperative preimplant CAS-derived stressed HKAA (R = 0.946). However, there was no correlation between the postoperative WB LLR HKAA and the postimplant insertion HKAA as measured intraoperatively via CAS for either a "resting" or "stressed" position of the operated knee (R = 0.165 and R = 0.041, respectively). Thus, the interpretation of intraoperative alignment data is potentially problematic. Despite technological advances in the development and utilization of computer navigation and robotics in arthroplasty to help obtain the optimal alignment, it would seem apparent from our study that this alignment does not correlate to upright stance postoperatively. Surgeons should apply caution to the strength of assumptions they place on intraoperative coronal plane alignment findings.

Supratrochlear Rim is Correlated with Isolated Patellar Chondromalacia on Magnetic Resonance Imaging of the Knee.

Purpose: To investigate the relationship between the supratrochlear rim and isolated patellar chondromalacia (PC) using magnetic resonance imaging (MRI) scans of the knee. Methods: Patients without patellofemoral pain (control group) and patients with patellofemoral pain and diagnosed with stage III or IV PC based on MRI (defect group) were retrospectively identified. Patients with a history of patellar subluxation were excluded. We used patient MRI scans to perform 20 anatomical measurements of the patellofemoral joint. We also performed 2 measurements of the anterior femoral curvature. A total of 30 patients (29 ± 8.7 years) were in the control group, and 20 patients were in the defect group (29.4 ± 9.7 years). Results: The maximum curvature (P < .001) and mean curvature (P < .001) of the anterior femoral condyle were found statistically significantly different between the groups. Patellotrochlear index (P = .03) and Insall-Salvati index (P < .001) were also found statistically significantly different between the 2 groups. Patella type III and trochlear dysplasia grade B were found more common in the defect group. Conclusions: In this Level III prognostic, case-control study, we have shown through MRI knee measurements that the isolated patellar chondromalacia in patients without a history of patellar subluxation and dislocation is correlated with the increased anterior femoral curvature in combination with patella alta.

A population-based epidemiological and health economic analysis of fracture-related infection.

Aims: The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). Methods: This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. Results: There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. Conclusion: The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies.

A tumour-spheroid manufacturing and cryopreservation process that yields a highly reproducible product ready for direct use in drug screening assays.

If it were possible to purchase tumour-spheroids as a standardised product, ready for direct use in assays, this may contribute to greater research reproducibility, potentially reducing costs and accelerating outcomes. Herein, we describe a workflow where uniformly sized cancer tumour-spheroids are mass-produced using microwell culture, cryopreserved with high viability, and then cultured in neutral buoyancy media for drug testing. C4-2B prostate cancer or MCF-7 breast cancer cells amalgamated into uniform tumour-spheroids after 48 h of culture. Tumour-spheroids formed from 100 cells each tolerated the cryopreservation process marginally better than tumour-spheroids formed from 200 or 400 cells. Post-thaw, tumour-spheroid metabolic activity was significantly reduced, suggesting mitochondrial damage. Metabolic function was rescued by thawing the tumour-spheroids into medium supplemented with 10 µM N-Acetyl-l-cysteine (NAC). Following thaw, the neutral buoyancy media, Happy Cell ASM, was used to maintain tumour-spheroids as discrete tissues during drug testing. Fresh and cryopreserved C4-2B or MCF-7 tumour-spheroids responded similarly to titrations of Docetaxel. This protocol will contribute to a future where tumour-spheroids may be available for purchase as reliable and reproducible products, allowing laboratories to efficiently replicate and build on published research, in many cases, making tumour-spheroids simply another cell culture reagent.

Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty.

BACKGROUND: The addition of vancomycin to beta-lactam prophylaxis in arthroplasty may reduce surgical-site infections; however, the efficacy and safety are unclear. METHODS: In this multicenter, double-blind, superiority, placebo-controlled trial, we randomly assigned adult patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization who were undergoing arthroplasty to receive 1.5 g of vancomycin or normal saline placebo, in addition to cefazolin prophylaxis. The primary outcome was surgical-site infection within 90 days after surgery. RESULTS: A total of 4239 patients underwent randomization. Among 4113 patients in the modified intention-to-treat population (2233 undergoing knee arthroplasty, 1850 undergoing hip arthroplasty, and 30 undergoing shoulder arthroplasty), surgical-site infections occurred in 91 of 2044 patients (4.5%) in the vancomycin group and in 72 of 2069 patients (3.5%) in the placebo group (relative risk, 1.28; 95% confidence interval [CI], 0.94 to 1.73; P = 0.11). Among patients undergoing knee arthroplasty, surgical-site infections occurred in 63 of 1109 patients (5.7%) in the vancomyin group and in 42 of 1124 patients (3.7%) in the placebo group (relative risk, 1.52; 95% CI, 1.04 to 2.23). Among patients undergoing hip arthroplasty, surgical-site infections occurred in 28 of 920 patients (3.0%) in the vancomyin group and in 29 of 930 patients (3.1%) in the placebo group (relative risk, 0.98; 95% CI, 0.59 to 1.63). Adverse events occurred in 35 of 2010 patients (1.7%) in the vancomycin group and in 35 of 2030 patients (1.7%) in the placebo group, including hypersensitivity reactions in 24 of 2010 patients (1.2%) and 11 of 2030 patients (0.5%), respectively (relative risk, 2.20; 95% CI, 1.08 to 4.49), and acute kidney injury in 42 of 2010 patients (2.1%) and 74 of 2030 patients (3.6%), respectively (relative risk, 0.57; 95% CI, 0.39 to 0.83). CONCLUSIONS: The addition of vancomycin to cefazolin prophylaxis was not superior to placebo for the prevention of surgical-site infections in arthroplasty among patients without known MRSA colonization. (Funded by the Australian National Health and Medical Research Council; Australian New Zealand Clinical Trials Registry number, ACTRN12618000642280.).

Three-Dimensional CT-Based Limb Length Evaluation Is Highly Dependent on Anatomical Landmark Selection and Pelvic Asymmetry.

Background: Pelvic skeletal asymmetry can result in rotational differences and morphologic bony prominence variance between the left and right hemipelvis. When selecting bony reference points for modern computed tomography-based robotic total hip arthroplasty planning, it is unclear which bony landmarks are the most reliable and accurate, especially in the presence of significant pelvic asymmetry. Methods: A retrospective study was conducted utilizing a database of computed tomography scans. Multiple bony landmarks in the pelvis and femur were selected for comparison, with the aim of measuring pelvic asymmetry. Specifically, the study measured the average difference in lateral offset between the left and right hemipelvis caused by pelvic asymmetry. Landmarks were also compared to determine the impact of pelvic asymmetry on hip length, femur length, and limb length discrepancies. Furthermore, a scenario was simulated in the software whereby a total hip replacement was inserted, potentially changing the hip length. The impact of pelvic reference point selection on the measurement of this simulated change in hip length was examined. Results: This study population showed widespread pelvic asymmetry. The anatomical landmarks of the opposite side cannot be relied upon for predicting the anatomy of the affected side. The center of rotation axis is more reliable than the inferior obturator foramen axis for hip length discrepancy due to pelvic asymmetry (P < .05). Conclusions: Current computer-assisted surgery THR software reports measurements of global offset and hip length that do not consider pelvic asymmetry. Surgeons are not given confidence ranges to represent the potential impact of asymmetry on the global offset and hip length values. Surgeons following these numbers to guide implant position may incur implant placement error should significant pelvic asymmetry be present in a given patient.

Spatial distribution of elements during osteoarthritis disease progression using synchrotron X-ray fluorescence microscopy.

The osteochondral interface is a thin layer that connects hyaline cartilage to subchondral bone. Subcellular elemental distribution can be visualised using synchrotron X-ray fluorescence microscopy (SR-XFM) (1 µm). This study aims to determine the relationship between elemental distribution and osteoarthritis (OA) progression based on disease severity. Using modified Mankin scores, we collected tibia plates from 9 knee OA patients who underwent knee replacement surgery and graded them as intact cartilage (non-OA) or degraded cartilage (OA). We used a tape-assisted system with a silicon nitride sandwich structure to collect fresh-frozen osteochondral sections, and changes in the osteochondral unit were defined using quantified SR-XFM elemental mapping at the Australian synchrotron's XFM beamline. Non-OA osteochondral samples were found to have significantly different zinc (Zn) and calcium (Ca) compositions than OA samples. The tidemark separating noncalcified and calcified cartilage was rich in zinc. Zn levels in OA samples were lower than in non-OA samples (P = 0.0072). In OA samples, the tidemark had less Ca than the calcified cartilage zone and subchondral bone plate (P < 0.0001). The Zn-strontium (Sr) colocalisation index was higher in OA samples than in non-OA samples. The lead, potassium, phosphate, sulphur, and chloride distributions were not significantly different (P > 0.05). In conclusion, SR-XFM analysis revealed spatial elemental distribution at the subcellular level during OA development.

SP7 gene silencing dampens bone marrow stromal cell hypertrophy, but it also dampens chondrogenesis.

For bone marrow stromal cells (BMSC) to be useful in cartilage repair their propensity for hypertrophic differentiation must be overcome. A single day of TGF-ß1 stimulation activates intrinsic signaling cascades in BMSCs which subsequently drives both chondrogenic and hypertrophic differentiation. TGF-ß1 stimulation upregulates SP7, a transcription factor known to contribute to hypertrophic differentiation, and SP7 remains upregulated even if TGF-ß1 is subsequently withdrawn from the chondrogenic induction medium. Herein, we stably transduced BMSCs to express an shRNA designed to silence SP7, and assess the capacity of SP7 silencing to mitigate hypertrophy. SP7 silencing dampened both hypertrophic and chondrogenic differentiation processes, resulting in diminished microtissue size, impaired glycosaminoglycan production and reduced chondrogenic and hypertrophic gene expression. Thus, while hypertrophic features were dampened by SP7 silencing, chondrogenic differentation was also compromised. We further investigated the role of SP7 in monolayer osteogenic and adipogenic cultures, finding that SP7 silencing dampened characteristic mineralization and lipid vacuole formation, respectively. Overall, SP7 silencing affects the trilineage differentiation of BMSCs, but is insufficient to decouple BMSC hypertrophy from chondrogenesis. These data highlight the challenge of promoting BMSC chondrogenesis whilst simultaneously reducing hypertrophy in cartilage tissue engineering strategies.

Downsizing and minimising medialisation of the acetabular component: Novel technique to preserve bone in THA.

Standard practice for acetabular component placement in total hip arthroplasty (THA) is to medialise the acetabular component. Bone preservation techniques during primary THA are beneficial for possible future revisions. The goal of this study is to examine the effect of downsizing and minimising medialisation of the acetabular component on bone resection volume. The volume of bone resected during acetabular preparation for different sizes of components was calculated and the volume of bone preserved by downsizing the cup was determined. Minimising medialisation of the acetabular component by 1-3 mm from the true floor was calculated. Absolute values and percentage of bone volume preserved when acetabular components are downsized or less medialised is presented. Downsizing the acetabular component by one size (2 mm) preserves between 2.6 cm3 (size 40 vs 42) and 8.4 cm3 (size 72 vs 74) of bone volume and consistently reduces resected bone volume by at least 35% (range 35.2%-37.5%). Similarly, reducing medialisation of a 56 mm acetabular cup (as an example of a commonly implanted component) by 3 mm reduces bone loss by 5.9 cm3- 44% less bone volume resection. Downsizing and minimising medialisation of the cup in THA substantially preserves bone which may benefit future revision surgeries. Surgeons could consider implanting the smallest acceptable acetabular shell to preserve bone without compromising on head size.

One step surgical scene restoration for robot assisted minimally invasive surgery.

Minimally invasive surgery (MIS) offers several advantages to patients including minimum blood loss and quick recovery time. However, lack of tactile or haptic feedback and poor visualization of the surgical site often result in some unintentional tissue damage. Visualization aspects further limits the collection of imaged frame contextual details, therefore the utility of computational methods such as tracking of tissue and tools, scene segmentation, and depth estimation are of paramount interest. Here, we discuss an online preprocessing framework that overcomes routinely encountered visualization challenges associated with the MIS. We resolve three pivotal surgical scene reconstruction tasks in a single step; namely, (i) denoise, (ii) deblur, and (iii) color correction. Our proposed method provides a latent clean and sharp image in the standard RGB color space from its noisy, blurred, and raw inputs in a single preprocessing step (end-to-end in one step). The proposed approach is compared against current state-of-the-art methods that perform each of the image restoration tasks separately. Results from knee arthroscopy show that our method outperforms existing solutions in tackling high-level vision tasks at a significantly reduced computation time.

Microtissue Culture Provides Clarity on the Relative Chondrogenic and Hypertrophic Response of Bone-Marrow-Derived Stromal Cells to TGF-ß1, BMP-2, and GDF-5.

Chondrogenic induction of bone-marrow-derived stromal cells (BMSCs) is typically accomplished with medium supplemented with growth factors (GF) from the transforming growth factor-beta (TGF-ß)/bone morphogenetic factor (BMP) superfamily. In a previous study, we demonstrated that brief (1-3 days) stimulation with TGF-ß1 was sufficient to drive chondrogenesis and hypertrophy using small-diameter microtissues generated from 5000 BMSC each. This biology is obfuscated in typical large-diameter pellet cultures, which suffer radial heterogeneity. Here, we investigated if brief stimulation (2 days) of BMSC microtissues with BMP-2 (100 ng/mL) or growth/differentiation factor (GDF-5, 100 ng/mL) was also sufficient to induce chondrogenic differentiation, in a manner comparable to TGF-ß1 (10 ng/mL). Like TGF-ß1, BMP-2 and GDF-5 are reported to stimulate chondrogenic differentiation of BMSCs, but the effects of transient or brief use in culture have not been explored. Hypertrophy is an unwanted outcome in BMSC chondrogenic differentiation that renders engineered tissues unsuitable for use in clinical cartilage repair. Using three BMSC donors, we observed that all GFs facilitated chondrogenesis, although the efficiency and the necessary duration of stimulation differed. Microtissues treated with 2 days or 14 days of TGF-ß1 were both superior at producing extracellular matrix and expression of chondrogenic gene markers compared to BMP-2 and GDF-5 with the same exposure times. Hypertrophic markers increased proportionally with chondrogenic differentiation, suggesting that these processes are intertwined for all three GFs. The rapid action, or "temporal potency", of these GFs to induce BMSC chondrogenesis was found to be as follows: TGF-ß1 > BMP-2 > GDF-5. Whether briefly or continuously supplied in culture, TGF-ß1 was the most potent GF for inducing chondrogenesis in BMSCs.

The Cost Effectiveness of Unicompartmental versus Total Knee Arthroplasty.

This study examines the potential cost savings for the health system and the community in a broadly accessible model through the increased utilization of unicompartmental knee arthroplasty (UKA) using robotic arm-assisted UKA (raUKA) versus conventional total knee arthroplasty (cTKA). We retrospectively reviewed 240 patients where the first 120 consecutive raUKA performed during this period were matched to 120 cTKAs. Clinical data from the medical records and costs for procedure for each component were collected. Bivariate analyses were performed on the data to determine if there were statistically significant differences by surgery type in clinical outcomes and financial costs. There was a significantly lower cost incurred for raUKA versus cTKA with an average saving of AU$7,179 per case. The operating time (86.0 vs. 75.9 minutes; p = 0.004) was significantly higher for raUKA, but the length of stay was significantly lower (1.8 vs. 4.8 days; p < 0.001). There was a significant difference in the use of opioids between raUKA and cTKA (125.0 morphine equivalent [ME] vs. 522.1 ME, p < 0.001). This study demonstrated that the use of raUKA rather than cTKA in suitably indicated patients may realize significant cost savings.

Inflammatory macrophages interrupt osteocyte maturation and mineralization via regulating the Notch signaling pathway.

BACKGROUND: It is well-known that both macrophages and osteocytes are critical regulators of osteogenesis and osteoclastogenesis, yet there is limited understanding of the macrophage-osteocyte interaction, and how their crosstalk could affect bone homeostasis and mineralization. This research therefore aims to investigate the effects of macrophage polarization on osteocyte maturation and mineralization process. METHODS: A macrophage-derived conditioned medium based osteocyte culture was set up to investigate the impact of macrophages on osteocyte maturation and terminal mineralization. Surgically induced osteoarthritis (OA) rat model was used to further investigate the macrophage-osteocyte interaction in inflammatory bone remodeling, as well as the involvement of the Notch signaling pathway in the mineralization process. RESULTS: Our results identified that osteocytes were confined in an immature stage after the M1 macrophage stimulation, showing a more rounded morphology, higher expression of early osteocyte marker E11, and significantly lower expression of mature osteocyte marker DMP1. Immature osteocytes were also found in inflammatory bone remodeling areas, showing altered morphology and mineralized structures similar to those observed under the stimulation of M1 macrophages in vitro, suggesting that M1 macrophages negatively affect osteocyte maturation, leading to abnormal mineralization. The Notch signaling pathway was found to be down regulated in M1 macrophage-stimulated osteocytes as well as osteocytes in inflammatory bone. Overexpression of the Notch signaling pathway in osteocytes showed a significant circumvention on the negative effects from M1 macrophage. CONCLUSION: Taken together, our findings provide valuable insights into the mechanisms involved in abnormal bone mineralization under inflammatory conditions.

Impaction Bone Grafting with Low Dose Irradiated Freeze-Dried Allograft Bone for Acetabular Reconstruction.

OBJECTIVE: Reconstruction of acetabular defects has been extremely challenging in both primary and revision total hip arthroplasty (THA). Impaction bone grafting (IBG) can restore the acetabulum bone mass and anatomically reconstruct the acetabulum. Our study aimed to report the short and medium-term clinical and radiographic outcomes of IBG for acetabular reconstruction in the cemented THA in the Chinese population. METHODS: This was a single-center retrospective review enrolling 57 patients between May 2013 and July 2019. The patients with acetabular defects were treated with IBG, using low dose irradiated freeze-dried allograft bone with or without autograft bone, in the cemented THA performed by one senior surgeon. Harris hip score (HHS), standard pelvis anterior-posterior radiograph and lateral hip radiograph were obtained before operation and at 1 week, 3 months, 12 months, and yearly. Graft osteointegration was evaluated by Oswestry's criteria, and complication was documented at the last follow-up. Independent sample ANOVA test and Pearson chi-square tests are used for statistical analysis. RESULTS: There were 61 hips in 57 patients. The average follow-up time was 35.59 months (5-77 months). According to AAOS classification, a total of 18 hips were identified as segmental bone deficiency (type I), with 21 and 22 hips for cavitary bone deficiency (type II) and the combined bone deficiency (type III), respectively. The average HHS was improved from 44.49 (range: 32-58) preoperatively to 86.98 (range: 78-93) postoperatively. Graft osteointegration was satisfactory (Oswestry score ≥2) in all patients. No dislocation occurred in the 57 patients (61 hips) during follow-up. Although one cup migrated, no revision, re-revision, radiographic loosening, graft bone lysis, or postoperative complications were detected at the final follow-up. CONCLUSIONS: IBG with low-dose irradiated freeze-dried allograft bone in acetabular bone defect reconstruction is a reliable technique for restoring acetabular bone defects in THA.

Obesity, Inflammation, and Immune System in Osteoarthritis.

Obesity remains the most important risk factor for the incidence and progression of osteoarthritis (OA). The leading cause of OA was believed to be overloading the joints due to excess weight which in turn leads to the destruction of articular cartilage. However, recent studies have proved otherwise, various other factors like adipose deposition, insulin resistance, and especially the improper coordination of innate and adaptive immune responses may lead to the initiation and progression of obesity-associated OA. It is becoming increasingly evident that multiple inflammatory cells are recruited into the synovial joint that serves an important role in pathological changes in the synovial joint. Polarization of macrophages and macrophage-produced mediators are extensively studied and linked to the inflammatory and destructive responses in the OA synovium and cartilage. However, the role of other major innate immune cells such as neutrophils, eosinophils, and dendritic cells in the pathogenesis of OA has not been fully evaluated. Although cells of the adaptive immune system contribute to the pathogenesis of obesity-induced OA is still under exploration, a quantity of literature indicates OA synovium has an enriched population of T cells and B cells compared with healthy control. The interplay between a variety of immune cells and other cells that reside in the articular joints may constitute a vicious cycle, leading to pathological changes of the articular joint in obese individuals. This review addresses obesity and the role of all the immune cells that are involved in OA and summarised animal studies and human trials and knowledge gaps between the studies have been highlighted. The review also touches base on the interventions currently in clinical trials, different stages of the testing, and their shortcomings are also discussed to understand the future direction which could help in understanding the multifactorial aspects of OA where inflammation has a significant function.

Prevalence and determinants of physical activity, sedentary behaviour and fatigue five years after total knee replacement.

OBJECTIVE: To determine the prevalence and predictors of physical activity, sedentary behaviour and fatigue five years after total knee replacement surgery. DESIGN: A longitudinal cohort study. SETTING: Community-dwelling adults who had previously undergone total knee replacement. METHODS: Five-year follow-up questionnaire data were obtained from participants previously enrolled in a randomised controlled trial examining rehabilitation after total knee replacement. Main study outcomes at one year did not differ between randomisation groups, hence data were pooled for the present longitudinal analysis. Before and one and five years after surgery, participants completed questionnaires (Active Australia Survey, WOMAC, SF12 v2, demographics and fatigue). RESULTS: 272/422 community-dwelling adults (45-74 years) completed the questionnaires at five years. Excessive sedentary behaviour was evident in 91% of the cohort, predicted by excessive sedentary behaviour and lack of energy at one year. Inadequate physical activity at five years was evident for 59% of the cohort, predicted by higher fatigue and comorbidity scores pre-surgery and inadequate physical activity at one year. Just under half (47%) of the cohort experienced clinically-important fatigue at five years, predicted by clinically-important fatigue before and one year after surgery, lack of sleep before surgery and physical activity one year after surgery. CONCLUSION: Documenting physical activity, sedentary behaviour and fatigue before and one year after knee replacement is important to identify those at risk of longer-term inadequate physical activity, excessive sedentary behaviour and clinically-important fatigue. Interventions to maintain activity and reduce sedentary behaviour are needed to reap the potential health benefits of total knee replacement surgery.

Inhibition of BMP signaling with LDN 193189 can influence bone marrow stromal cell fate but does not prevent hypertrophy during chondrogenesis.

Bone morphogenetic protein (BMP) cascades are upregulated during bone marrow-derived stromal cell (BMSC) chondrogenesis, contributing to hypertrophy and preventing effective BMSC-mediated cartilage repair. Previous work demonstrated that a proprietary BMP inhibitor prevented BMSC hypertrophy, yielding stable cartilage tissue. Because of the significant therapeutic potential of a molecule capable of hypertrophy blockade, we evaluated the capacity of a commercially available BMP type I receptor inhibitor with similar properties, LDN 193189, to prevent BMSC hypertrophy. Using 14-day microtissue chondrogenic induction cultures we found that LDN 193189 permitted BMSC chondrogenesis but did not prevent hypertrophy. LDN 193189 was sufficiently potent to counter mineralization and adipogenesis in response to exogenous BMP-2 in osteogenic induction cultures. LDN 193189 did not modify BMSC behavior in adipogenic induction cultures. Although LDN 193189 is effective in countering BMP signaling in a manner that influences BMSC fate, this blockade is insufficient to prevent hypertrophy.

The deterioration of calcified cartilage integrity reflects the severity of osteoarthritis-A structural, molecular, and biochemical analysis.

The calcified cartilage zone (CCZ) is a thin interlayer between the hyaline articular cartilage and the subchondral bone and plays an important role in maintaining the joint homeostasis by providing biological and mechanical support from unmineralized cartilage to the underlying mineralized subchondral bone. The hallmark of CCZ characteristics in osteoarthritis (OA) is less well known. The aim of our study is to evaluate the structural, molecular, and biochemical composition of CCZ in tissues affected by primary knee OA and its relationship with disease severity. We collected osteochondral tissue samples stratified according to disease severity, from 16 knee OA patients who underwent knee replacement surgery. We also used meniscectomy-induced rat samples to confirm the pathophysiologic changes of human samples. We defined the characteristics of the calcified cartilage layer using a combination of morphological, biochemical, proteomic analyses on laser micro-dissected tissue. Our results demonstrated that the Calcium/Phosphate ratio is unchanged during the OA progression, but the calcium-binding protein and cadherin binding protein, as well as carbohydrate metabolism-related proteins, undergo significant changes. These changes were further accompanied by thinning of the CCZ, loss of collagen and proteoglycan content, the occurrence of the endochondral ossification, neovasculature, loss of the elastic module, loss of the collagen direction, and increase of the tortuosity indicating an altered structural and mechanical properties of the CCZ in OA. In conclusion, our results suggest that the calcified cartilage changes can reflect the disease progression.

Clinical and radiological outcomes of robotic-assisted unicompartmental knee arthroplasty: Early lessons from the first 100 consecutive knees in 85 patients.

INTRODUCTION: Robotic-assisted unicompartmental knee arthroplasty (UKA) is associated with improved component positioning and comparable short- and mid-term implant survivorship with manual UKA. This study aims to evaluate clinical and radiological outcomes following robotic-assisted UKA as well as any potential learning-curves associated with the introduction of such new technology. METHODS: Prospective study of patients undergoing robotic-assisted UKA. Outcome measures were patient-reported outcome measures (PROMs) including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society Score (KSS) and Oxford Knee Score (OKS), complications, implant survivorship, component positioning and learning curve. RESULTS: Eighty-five patients comprising 100 knees were recruited and followed up for 21.0 ± 4.3 months. At two years, there were significant and sustained improvements in PROMs and 100% implant survivorship rate. A high degree of implant accuracy was achieved with the robotic system. A cumulative learning curve of 20 cases was noted. CONCLUSION: Robotic-assisted UKA achieves excellent implant accuracy and clinical outcomes in the short-term. Long-term follow up is needed to evaluate this relationship.