Quantitative Magnetic Resonance Imaging of Lateral Compartment Articular Cartilage After Lateral Extra-articular Tenodesis.

BACKGROUND: Concerns have arisen that anterior cruciate ligament reconstruction (ACLR) with lateral extra-articular tenodesis (LET) may accelerate the development of posttraumatic osteoarthritis in the lateral compartment of the knee. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate whether the augmentation of ACLR with LET affects the quality of lateral compartment articular cartilage on magnetic resonance imaging (MRI) at 2 years postoperatively. We hypothesized that there would be no difference in T1rho and T2 relaxation times when comparing ACLR alone with ACLR + LET. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A consecutive subgroup of patients at the Fowler Kennedy Sport Medicine Clinic participating in the STABILITY 1 Study underwent bilateral 3-T MRI at 2 years after surgery. The primary outcome was T1rho and T2 relaxation times. Articular cartilage in the lateral compartment was manually segmented into 3 regions of the tibia (lateral tibia [LT]-1 to LT-3) and 5 regions of the femur (lateral femoral condyle [LFC]-1 to LFC-5). Analysis of covariance was used to compare relaxation times between groups, adjusted for lateral meniscal tears and treatment, cartilage and bone marrow lesions, contralateral relaxation times, and time since surgery. Semiquantitative MRI scores according to the Anterior Cruciate Ligament OsteoArthritis Score were compared between groups. Correlations were used to determine the association between secondary outcomes (including results of the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, Lower Extremity Functional Scale, 4-Item Pain Intensity Measure, hop tests, and isokinetic quadriceps and hamstring strength tests) and cartilage relaxation. RESULTS: A total of 95 participants (44 ACLR alone, 51 ACLR + LET) with a mean age of 18.8 years (61.1% female [58/95]) underwent 2-year MRI (range, 20-36 months). T1rho relaxation times were significantly elevated for the ACLR + LET group in LT-1 (37.3 ± 0.7 ms vs 34.1 ± 0.8 ms, respectively; P = .005) and LFC-2 (43.9 ± 0.9 ms vs 40.2 ± 1.0 ms, respectively; P = .008) compared with the ACLR alone group. T2 relaxation times were significantly elevated for the ACLR + LET group in LFC-1 (51.2 ± 0.7 ms vs 49.1 ± 0.7 ms, respectively; P = .03) and LFC-4 (45.9 ± 0.5 ms vs 44.2 ± 0.6 ms, respectively; P = .04) compared with the ACLR alone group. All effect sizes were small to medium. There was no difference in Anterior Cruciate Ligament OsteoArthritis Scores between groups (P = .99). Weak negative associations (rs = -0.27 to -0.22; P < .05) were found between relaxation times and quadriceps and hamstring strength in the anterolateral knee, while all other correlations were nonsignificant (P > .05). CONCLUSION: Increased relaxation times demonstrating small to medium effect sizes suggested early biochemical changes in articular cartilage of the anterolateral compartment in the ACLR + LET group compared with the ACLR alone group. Further evidence and long-term follow-up are needed to better understand the association between these results and the potential risk of the development of osteoarthritis in our patient cohort.

Detection and Characterization of Endplate Structural Defects on CT: A Diagnostic Accuracy Study.

STUDY DESIGN: Diagnostic test study. OBJECTIVE: To determine the reliability and validity or diagnostic accuracy of two previously described endplate structural defect (EPSD) assessment methods. SUMMARY OF BACKGROUND DATA: Studies of EPSD may further the understanding of pathoanatomical mechanisms underlying back pain. However, clinical imaging methods used to document EPSD have not been validated, leaving uncertainty about what the observations represent. METHODS: Using an evaluation manual, 418 endplates on CT sagittal slices obtained from 19 embalmed cadavers (9 men and 10 women, aged 62-91 y) were independently assessed by two experienced radiologists and a novice for EPSD using the two methods. The corresponding micro-CT (µCT) from the harvested T7-S1 spines were assessed by another independent rater with excellent intra-rater reliability (Kappa=0.96). RESULTS: Inter-rater reliability was good for presence (Kappa=0.60-0.69) and fair for specific phenotypes (Kappa=0.43-0.58) of EPSD. Erosion, for which the Brayda-Bruno classification lacked a category, was mainly (82.8%) classified as wavy/irregular, while many notched defects (n=15, 46.9%) and Schmorl's nodes (n=45, 79%) were recorded as focal defects using Feng's classification. When compared to µCT, endplate fractures (n=53) and corner defects (n=28) were routinely missed on CT. Endplates classified as wavy/irregular on CT corresponded to erosion (n=29, 21.2%), jagged defects (n=21, 15.3%), calcification (n=19, 13.9%), and other phenotypes on µCT. Some focal defects on CT represented endplate fractures (n=21, 27.6%) on µCT. Overall, with respect to the presence of an EPSD, there was a sensitivity of 70.9% and specificity of 79.1% using Feng's method, and 79.5% and 57.5% using Brayda-Bruno's. Poor to fair inter-rater reliability (k=0.26-0.47) was observed for defect dimensions. CONCLUSION: There was good inter-rater reliability and evidence of criterion validity supporting assessments of EPSD presence using both methods. However, neither method contained all needed EPSD phenotypes for optimal sensitivity, and specific phenotypes were often misclassified.

Metal Organic Framework-Incorporated Three-Dimensional (3D) Bio-Printable Hydrogels to Facilitate Bone Repair: Preparation and In Vitro Bioactivity Analysis.

Hydrogels are three-dimensional (3D) water-swellable polymeric matrices that are used extensively in tissue engineering and drug delivery. Hydrogels can be conformed into any desirable shape using 3D bio-printing, making them suitable for personalized treatment. Among the different 3D bio-printing techniques, digital light processing (DLP)-based printing offers the advantage of quickly fabricating high resolution structures, reducing the chances of cell damage during the printing process. Here, we have used DLP to 3D bio-print biocompatible gelatin methacrylate (GelMA) scaffolds intended for bone repair. GelMA is biocompatible, biodegradable, has integrin binding motifs that promote cell adhesion, and can be crosslinked easily to form hydrogels. However, GelMA on its own is incapable of promoting bone repair and must be supplemented with pharmaceutical molecules or growth factors, which can be toxic or expensive. To overcome this limitation, we introduced zinc-based metal-organic framework (MOF) nanoparticles into GelMA that can promote osteogenic differentiation, providing safer and more affordable alternatives to traditional methods. Incorporation of this nanoparticle into GelMA hydrogel has demonstrated significant improvement across multiple aspects, including bio-printability, and favorable mechanical properties (showing a significant increase in the compressive modulus from 52.14 ± 19.42 kPa to 128.13 ± 19.46 kPa with the addition of ZIF-8 nanoparticles). The designed nanocomposite hydrogels can also sustain drug (vancomycin) release (maximum 87.52 ± 1.6% cumulative amount) and exhibit a remarkable ability to differentiate human adipose-derived mesenchymal stem cells toward the osteogenic lineage. Furthermore, the formulated MOF-integrated nanocomposite hydrogel offers the unique capability to coat metallic implants intended for bone healing. Overall, the remarkable printability and coating ability displayed by the nanocomposite hydrogel presents itself as a promising candidate for drug delivery, cell delivery and bone tissue engineering applications.

Thoracolumbar Vertebral Endplate Defect Morphology: A Descriptive Study of Human Cadaveric Spines Using Micro-Computed Tomography.

STUDY DESIGN: A descriptive, cross-sectional cadaver study. OBJECTIVE: This study aimed to provide a thorough depiction of vertebral endplate defects classified based on their morphologic features and reported with respect to size, location, and prevalence in the human cadaveric spines of older adults. SUMMARY OF BACKGROUND DATA: Back pain has been associated with vertebral endplate defects; however, findings have been inconsistent. This is partially due to miscommunication surrounding the classification of endplate defects observed using clinical imaging, and limited knowledge of the types of defects present on the endplate and their prevalence. A comprehensive study of vertebral endplates is needed to clarify types of structural defects, their character, and prevalence. MATERIALS AND METHODS: Using micro-computed tomography, 3-dimensional reconstructed images were created of 409 endplates from 19 cadaveric spines (9 men and 10 women; aged 62-91; T6-S1). Endplate defects were categorized based on their morphology, size, and location to investigate distribution patterns. RESULTS: Seven types of endplate defects were identified: Schmorl nodes, corner fracture or limbus vertebra, other fractures, erosion, jagged surface, calcification, and depressions. Defects were identified on 63.6% of endplates. Multiple defects were present on 19.1% of endplates. Fracture and erosion were the most common defect types. Defects were more common on the endplate cranial to the intervertebral disc and in male specimens ( P = 0.01). Defects were larger in the lumbar spine and the "total area of endplate defect" was larger on the cranial than the caudal endplate in the thoracic spine ( P < 0.05). CONCLUSION: This is the first study of which we are aware that provides a thorough depiction of the morphology and distribution of endplate defects across the entire lower thoracic and lumbar spine (T6-S1) using micro-computed tomography. Results support the presence of several distinct endplate defect phenotypes with different prevalence rates and provide a reference when considering endplate defects in the elderly.

Effects of risk factors on evoked pain patterns in rat models of experimental knee osteoarthritis.

Pain experiences in patients with knee osteoarthritis (OA) may be influenced differently by OA risk factors, reducing the translatability of preclinical research into the clinic. Our objective was to contrast evoked pain patterns after exposure to different OA risk factors including acute joint trauma, chronic instability, or obesity/metabolic syndrome using rat models of experimental knee OA. We tested longitudinal patterns of evoked pain behaviors (knee pressure pain threshold and hindpaw withdrawal threshold) in young male rats exposed to different OA-inducing risk factors including (1) nonsurgical joint trauma (impact-induced anterior cruciate ligament (ACL) rupture); (2) surgical joint destabilization (ACL + medial meniscotibial ligament transection); and (3) high fat/sucrose (HFS) diet-induced obesity. Histopathology for synovitis, cartilage damage, and subchondral bone morphology was performed. Pressure pain threshold was reduced (more pain) most, and earlier by joint trauma (Week 4-12) and HFS (Week 8-28) than by joint destabilization (Week 12). Hindpaw withdrawal threshold was reduced transiently after joint trauma (Week 4), with smaller and later reductions after joint destabilization (Week 12), but not with HFS. Synovial inflammation occurred at Week 4 after joint trauma and instability but only coincided with pain behaviors after joint trauma. Cartilage and bone histopathology were most severe after joint destabilization and least severe with HFS. The pattern, intensity, and timing of evoked pain behaviors varied due to OA risk factor exposure and were inconsistently associated with histopathological OA features. These findings may help to explain the challenges with translating preclinical OA pain research to multimorbid clinical OA contexts.

Induction Heating Triggers Antibiotic Release and Synergistic Bacterial Killing on Polymer-Coated Titanium Surfaces.

Infection is a major complication associated with orthopedic implants. It often involves the development of biofilms on metal substrates, which act as barriers to the host's immune system and systemic antibiotic treatment. The current standard of treatment is revision surgery, often involving the delivery of antibiotics through incorporation into bone cements. However, these materials exhibit sub-optimal antibiotic release kinetics and revision surgeries have drawbacks of high cost and recovery time. Herein, a new approach is presented using induction heating of a metal substrate, combined with an antibiotic-loaded poly(ester amide) coating undergoing a glass transition just above physiological temperature to enable thermally triggered antibiotic release. At normal physiological temperature, the coating provides a rifampicin depot for >100 days, while heating of the coating accelerates drug release, with >20% release over a 1-h induction heating cycle. Induction heating or antibiotic-loaded coating alone each reduce Staphylococcus aureus (S. aureus) viability and biofilm formation on Ti, but the combination causes synergistic killing of S. aureus as measured by crystal violet staining, determination of bacterial viability (>99.9% reduction), and fluorescence microscopy of bacteria on surfaces. Overall, these materials provide a promising platform enabling externally triggered antibiotic release to prevent and/or treat bacterial colonization of implants.

Assessing the Sensitivity of Dual-Energy Computed Tomography 3-Material Decomposition for the Detection of Gout.

OBJECTIVES: The aim of this study was to assess the accuracy and precision of a novel application of 3-material decomposition (3MD) with virtual monochromatic images (VMIs) in the dual-energy computed tomography (DECT) assessment of monosodium urate (MSU) and hydroxyapatite (HA) phantoms compared with a commercial 2-material decomposition (2MD) and dual-thresholding (DT) material decomposition methods. MATERIALS AND METHODS: Monosodium urate (0.0, 3.4, 13.3, 28.3, and 65.2 mg/dL tubes) and HA (100, 400, and 800 mg/cm 3 tubes) phantoms were DECT scanned individually and together in the presence of the foot and ankle of 15 subjects. The raw data were decomposed with 3MD-VMI, 2MD, and DT to produce MSU-only and HA-only images. Mean values of 10 × 10 × 10-voxel volumes of interest (244 µm 3 ) placed in each MSU and HA phantom well were obtained and compared with their known concentrations and across measurements with subjects' extremities to obtain accuracy and precision measures. A statistical difference was considered significant if P < 0.05. RESULTS: Compared with known phantom standards, 3MD-VMI was accurate for the detection of MSU concentrations as low as 3.4 mg/dL ( P = 0.75). In comparison, 2MD was limited to 13.3 mg/dL ( P = 0.06) and DT was unable to detect MSU concentrations below 65.2 mg/L ( P = 0.16). For the HA phantom, 3MD-VMI and 2MD were accurate for all concentrations including the lowest at 100 mg/cm 3 ( P = 0.63 and P = 0.55, respectively). Dual-thresholding was not useful for the decomposition of HA phantom. Precision was high for both 3MD-VMI and 2MD measurements for both MSU and HA phantoms. Qualitatively, 3MD-VMI MSU-only images demonstrated reduced beam-hardening artifact and voxel misclassification, compared with 2MD and DT. CONCLUSIONS: Three-material decomposition-VMI DECT is accurate for quantification of MSU and HA concentrations in phantoms and accurately detects a lower concentration of MSU than either 2MD or DT. For concentration measurements of both MSU and HA phantoms, 3MD-VMI and 2MD have high precision, but DT had limitations. Clinical implementation of 3MD-VMI DECT promises to improve the performance of this imaging modality for diagnosis and treatment monitoring of gout.

Effective magnetic susceptibility of 3D-printed porous metal scaffolds.

PURPOSE: 3D-printed porous metal scaffolds are a promising emerging technology in orthopedic implant design. Compared to solid metal implants, porous metal implants have lower magnetic susceptibility values, which have a direct impact on imaging time and image quality. The purpose of this study is to determine the relationship between porosity and effective susceptibility through quantitative estimates informed by comparing coregistered scanned and simulated field maps. METHODS: Five porous scaffold cylinders were designed and 3D-printed in titanium alloy (Ti-6Al-4V) with nominal porosities ranging from 60% to 90% using a cellular sheet-based gyroid design. The effective susceptibility of each cylinder was estimated by comparing acquired B0 field maps against simulations of a solid cylinder of varying assigned magnetic susceptibility, where the orientation and volume of interest of the simulations was informed by a custom alignment phantom. RESULTS: Magnitude images and field maps showed obvious decreases in artifact size and field inhomogeneity with increasing porosity. The effective susceptibility was found to be linearly correlated with porosity (R2  = 0.9993). The extrapolated 100% porous (no metal) magnetic susceptibility was -9.9 ppm, closely matching the expected value of pure water (-9 ppm), indicating a reliable estimation of susceptibility. CONCLUSION: Effective susceptibility of porous metal scaffolds is linearly correlated with porosity. Highly porous implants have sufficiently low effective susceptibilities to be more amenable to routine imaging with MRI.

Low-flow intussusception and metastable VEGFR2 signaling launch angiogenesis in ischemic muscle.

Efforts to promote sprouting angiogenesis in skeletal muscles of individuals with peripheral artery disease have not been clinically successful. We discovered that, contrary to the prevailing view, angiogenesis following ischemic muscle injury in mice was not driven by endothelial sprouting. Instead, real-time imaging revealed the emergence of wide-caliber, primordial conduits with ultralow flow that rapidly transformed into a hierarchical neocirculation by transluminal bridging and intussusception. This process was accelerated by inhibiting vascular endothelial growth factor receptor-2 (VEGFR2). We probed this response by developing the first live-cell model of transluminal endothelial bridging using microfluidics. Endothelial cells subjected to ultralow shear stress could reposition inside the flowing lumen as pillars. Moreover, the low-flow lumen proved to be a privileged location for endothelial cells with reduced VEGFR2 signaling capacity, as VEGFR2 mechanosignals were boosted. These findings redefine regenerative angiogenesis in muscle as an intussusceptive process and uncover a basis for its launch.

Novel quantification of the regional strain distribution in the anterior cruciate ligament in response to simulated loading using micro-CT imaging.

PURPOSE: A large percentage of anterior cruciate ligament (ACL) surgical reconstructions experience sub-optimal outcomes within 2 years. A potential factor contributing to poor outcomes is an incomplete understanding of micro-level, regional ACL biomechanics. This research aimed to demonstrate a minimally invasive method that uses micro-CT imaging to quantify regional ACL strains under clinically relevant joint loading. METHODS: A pattern of 0.8 mm diameter zirconium dioxide beads were arthroscopically inserted into four regions of the ACL of four cadaveric knee specimens (mean [SD] age = 59 [9] years). A custom micro-CT compatible joint motion simulator then applied clinically relevant joint loading conditions, while an image was acquired at each condition. From the resulting images, strains within each region were calculated using the centroid coordinates of each tissue-embedded bead. Strain repeatability was assessed using the mean intra-specimen standard deviation across repeated load applications. A one-way repeated measures ANOVA (α = 0.05) was used to determine regional strain variations. RESULTS: The mean intra-specimen standard deviation across repeated load application was ±0.003 strain for all specimens. No statistically significant differences were found between tissue regions, although medium and large effect sizes (0.095-0.450) suggest that these differences may be clinically relevant. CONCLUSIONS: The method presented here demonstrates a minimally invasive measurement of regional ACL strain under clinically relevant joint loads using micro-CT imaging. The strain measurements demonstrated excellent reliability across the five repeated load applications and suggest a non-homogenous distribution of strain through the ACL.

PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT.

Vascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

2021 Frank Stinchfield Award: A novel cemented hip hemiarthroplasty infection model with real-time in vivo imaging in rats : an animal study.

AIMS: The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. METHODS: Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. RESULTS: All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. CONCLUSION: This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9-16.

Accuracy and precision of image-based strain measurement using embedded radiopaque markers.

The purpose of this work was to assess the resolution to which micro-CT and intra-operative CT systems can quantify distances between radiopaque fiducial markers. Twenty-two markers were cast in a silicone phantom, then imaged at ten random rotations and translations within the field of view of a micro-CT and an intraoperative CT. A bounding box method and a mask-based weighted binary method were used to calculate the location of all markers in an image, then the Euclidian distance between neighbouring marker coordinates was calculated. The standard deviation in the inter-marker distance measurements from each of the marker position methods across the ten repeated trials was calculated for each marker identification method to provide a measure of the precision of the strain measurement with each scanner. The imaging systems measured 3D distances between markers to within 0.007 mm and 0.028 mm in the micro-CT and intra-operative CT, respectively, using the bounding box method, and to within 0.011 mm and 0.040 mm in the micro-CT and intra-operative systems, respectively, using the weighted-mask method. The bounding box method was found to be the most precise and is highly promising for applications in high resolution regional soft-tissue strain measurements.

Localized Oxygen Exchange Platform for Intravital Video Microscopy Investigations of Microvascular Oxygen Regulation.

Intravital microscopy has proven to be a powerful tool for studying microvascular physiology. In this study, we propose a gas exchange system compatible with intravital microscopy that can be used to impose gas perturbations to small localized regions in skeletal muscles or other tissues that can be imaged using conventional inverted microscopes. We demonstrated the effectiveness of this system by locally manipulating oxygen concentrations in rat extensor digitorum longus muscle and measuring the resulting vascular responses. A computational model of oxygen transport was used to partially validate the localization of oxygen changes in the tissue, and oxygen saturation of red blood cells flowing through capillaries were measured as a surrogate for local tissue oxygenation. Overall, we have demonstrated that this approach can be used to study dynamic and spatial responses to local oxygen challenges to the microenvironment of skeletal muscle.

No Difference in Ligamentous Strain or Knee Kinematics Between Rectangular or Cylindrical Femoral Tunnels During Anatomic ACL Reconstruction With a Bone-Patellar Tendon-Bone Graft.

BACKGROUND: As our understanding of anterior cruciate ligament (ACL) anatomy has evolved, surgical techniques to better replicate the native anatomy have been developed. It has been proposed that the introduction of a rectangular socket ACL reconstruction to replace a ribbon-shaped ACL has the potential to improve knee kinematics after ACL reconstruction. PURPOSE: To compare a rectangular femoral tunnel (RFT) with a cylindrical femoral tunnel (CFT) in terms of replicating native ACL strain and knee kinematics in a time-zero biomechanical anatomic ACL reconstruction model using a bone-patellar tendon-bone (BTB) graft. STUDY DESIGN: Controlled laboratory study. METHODS: In total, 16 fresh-frozen, human cadaveric knees were tested in a 5 degrees of freedom, computed tomography-compatible joint motion simulator. Knees were tested with the ACL intact before randomization to RFT or CFT ACL reconstruction using a BTB graft. An anterior translation load and an internal rotation moment were each applied at 0°, 30°, 60°, and 90° of knee flexion. A simulated pivot shift was performed at 0° and 30° of knee flexion. Ligament strain and knee kinematics were assessed using computed tomography facilitated by insertion of zirconium dioxide beads placed within the substance of the native ACL and BTB grafts. RESULTS: For the ACL-intact state, there were no differences between groups in terms of ACL strain or knee kinematics. After ACL reconstruction, there were no differences in ACL graft strain when comparing the RFT and CFT groups. At 60° of knee flexion with anterior translation load, there was significantly reduced strain in the reconstructed state ([mean ±standard deviation] CFT native, 2.82 ± 3.54 vs CFT reconstructed, 0.95 ± 2.69; RFT native, 2.77 ± 1.71 vs RFT reconstructed, 1.40 ± 1.76) independent of the femoral tunnel type. In terms of knee kinematics, there were no differences when comparing the RFT and CFT groups. Both reconstructive techniques were mostly effective in restoring native knee kinematics and ligament strain patterns as compared with the native ACL. CONCLUSION: In the time-zero biomechanical environment, similar graft strains and knee kinematics were achieved using RFT and CFT BTB ACL reconstructions. Both techniques appeared to be equally effective in restoring kinematics associated with the native ACL state. CLINICAL RELEVANCE: These data suggest that in terms of knee kinematics and graft strain, there is no benefit in performing the more technically challenging RFT as compared with a CFT BTB ACL reconstruction.

Effect of Memantine Treatment and Combination with Vitamin D Supplementation on Body Composition in the APP/PS1 Mouse Model of Alzheimer's Disease Following Chronic Vitamin D Deficiency.

BACKGROUND: Vitamin D deficiency and altered body composition are common in Alzheimer's disease (AD). Memantine with vitamin D supplementation can protect cortical axons against amyloid-ß exposure and glutamate toxicity. OBJECTIVE: To study the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on whole-body composition using a mouse model of AD. METHODS: Male APPswe/PS1dE9 mice were divided into four groups at 2.5 months of age: the control group (n = 14) was fed a standard diet throughout; the remaining mice were started on a vitamin D-deficient diet at month 6. The vitamin D-deficient group (n = 14) remained on the vitamin D-deficient diet for the rest of the study. Of the remaining two groups, one had memantine (n = 14), while the other had both memantine and 10 IU/g vitamin D (n = 14), added to their diet at month 9. Serum 25(OH)D levels measured at months 6, 9, 12, and 15 confirmed vitamin D levels were lower in mice on vitamin D-deficient diets and higher in the vitamin D-supplemented mice. Micro-computed tomography was performed at month 15 to determine whole-body composition. RESULTS: In mice deprived of vitamin D, memantine increased bone mineral content (8.7% increase, p < 0.01) and absolute skeletal tissue mass (9.3% increase, p < 0.05) and volume (9.2% increase, p < 0.05) relative to controls. This was not observed when memantine treatment was combined with vitamin D enrichment. CONCLUSION: Combination treatment of vitamin D and memantine had no negative effects on body composition. Future studies should clarify whether vitamin D status impacts the effects of memantine treatment on bone physiology in people with AD.

In vivo reverse total shoulder arthroplasty contact mechanics.

BACKGROUND: Several in vitro studies have investigated the biomechanics of reverse total shoulder arthroplasty (RTSA); however, few in vivo studies exist. The purpose of this study was to examine in vivo RTSA contact mechanics in clinically relevant arm positions. Our hypothesis was that contact would preferentially occur in the inferior region of the polyethylene liner. METHODS: Forty patients receiving a primary RTSA were recruited for a prospective cohort study. All patients received the same implant design with a nonretentive liner. Stereo radiographs were taken at maximal active range of motion. Model-based radiostereometric analysis was used to identify implant position. Contact area between the polyethylene and glenosphere was measured as the geometric intersection of the 2 components and compared with respect to polyethylene liner size, arm position, and relative position within the liner. RESULTS: There were no differences in the proportion of contact area in any arm position between polyethylene liner sizes, ranging from 30% ± 17% to 38% ± 23% for 36-mm liners and 32% ± 21% to 41% ± 25% for 42-mm liners. Contact was equally distributed between the superior and inferior halves of the liner at each arm position (P = .06-.79); however, greater contact area was observed in the outer radius of the liner when the arm was flexed (P = .002). CONCLUSION: This study highlights that contact mechanics are similar between 36- and 42-mm liners. Contact area is generally equally distributed throughout the liner across the range of motion and not preferentially in the inferior region as hypothesized.

Insertion of Small Diameter Radiopaque Tracking Beads into the Anterior Cruciate Ligament Results in Repeatable Strain Measurement Without Affecting the Material Properties.

The characterization of ligamentous soft tissue properties is limited by a lack of measurement methods capable of minimally-invasively quantifying regional strain. Previous implementations of radiographic imaging and tissue-embedded radiopaque markers demonstrated promising regional strain measurements, but found error associated with non-repeatable bead positions within the tissue after load application. No study has investigated the effects of cyclic loading on the strains measured within the tissue. The purpose of this study was to quantify the effect of joint loading on strain measurement using radiopaque markers and micro-computed tomography imaging. Six cadaveric porcine femur-anterior cruciate ligament-tibia complexes were instrumented with small diameter (0.8 mm) zirconium dioxide marker beads. The compound was imaged at 10 N then at 100 N of anterior force using micro-computed tomography. The bead positions in the images were used to calculate tissue strain between the 10 and 100 N anterior joint load conditions. Up to 100 intermediate joint cycles were applied, then images were acquired again at 10 and 100 N anterior force. No statistically significant difference was found between the strains measured before and after intermediate cycling (p > 0.05). This indicates that tissue loading did not introduce statistically significant changes to strains measured in tissue tested following this methodology.

Development of a Wireless Telemetry Sensor Device to Measure Load and Deformation in Orthopaedic Applications.

Due to sensor size and supporting circuitry, in-vivo load and deformation measurements are currently restricted to applications within larger orthopaedic implants. The objective of this study is to repurpose a commercially available low-power, miniature, wireless, telemetric, tire-pressure sensor (FXTH87) to measure load and deformation for future use in orthopaedic and biomedical applications. The capacitive transducer membrane was modified, and compressive deformation was applied to the transducer to determine the sensor signal value and the internal resistive force. The sensor package was embedded within a deformable enclosure to illustrate potential applications of the sensor for monitoring load. To reach the maximum output signal value, sensors required compressive deformation of 350 ± 24 µm. The output signal value of the sensor was an effective predictor of the applied load on a calibrated plastic strain member, over a range of 35 N. The FXTH87 sensor can effectively sense and transmit load-induced deformations. The sensor does not have a limit on loads it can measure, as long as deformation resulting from the applied load does not exceed 350 µm. The proposed device presents a sensitive and precise means to monitor deformation and load within small-scale, deformable enclosures.

Image-based design and 3D-metal printing of a rat hip implant for use in a clinically representative model of joint replacement.

The aim of this study was to obtain micro-computed tomography derived measurements of the rat proximal femur, to create parameterized rat hip implants that could be surgically installed in a clinically representative small animal model of joint replacement. The proximal femoral anatomy of N = 25 rats (male, Sprague-Dawley, 390-605 g) was quantified. Key measurements were used to parameterize computer-aided design models of monoblock rat femoral implants. Linear regression analysis was used to determine if rat hip dimensions could be predicted from animal weight. A correlation analysis was used to determine how implants could be scaled to create a range of sizes. Additive manufacturing (3D printing) was used to create implants in medical-grade metal alloys. Linear regressions comparing rat weight to femoral head diameter and neck-head axis length revealed a significant nonzero slope (P < .05). Pearson's correlation analysis revealed five significant correlations between key measurements in the rat femur (P < .05). Implants were installed into both cadaveric and live animals; iterative design modifications were made to prototypes based on these surgical findings. Animals were able to tolerate the installation of implants and were observed ambulating on their affected limbs postoperatively. Clinical significance: We have developed a preclinical rat hip hemiarthroplasty model using image-based and iterative design techniques to create 3D-metal printed implants in medical-grade metal alloys. Our findings support further development of this model for use as a low-cost translational test platform for preclinical orthopaedic research into areas such as osseointegration, metal-on-cartilage wear, and periprosthetic joint infection.