Explore the vast range of titles available.

Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold’s shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved. Cardiac repair usually requires highly invasive interventional procedures. Here, the authors develop an injectable shape-memory cardiac patch and demonstrated its applicability in a myocardial infarction model.

Integrins are a family of heterodimeric proteins expressed by cardiac fibroblasts and cardiomyocytes that provide critical adhesive and signaling functions through their interactions with the extracellular matrix (ECM) and the actin cytoskeleton. These adhesive processes are important for paracrine signaling, ECM homeostasis and for the intercellular interactions that impact cardiac cell biology and pathophysiological adaptation in disease. Despite considerable progress, our understanding of the interplay between cardiac cells, the ECM and integrins remains largely elusive. In this review, we examine the role of integrins in adhesive and signaling functions, and how these functions enable communication between cardiac fibroblasts, cardiomyocytes and the ECM. These processes strongly influence cardiac development and, later, the progression into cardiac disease. An improved understanding of this multi-dimensional system in cardiac tissues is needed to decipher the biological, spatiotemporal and mechanical cues that regulate cardiac health and the manifestation of cardiac disease. Greater insight into integrin function in cardiac tissues may also suggest new treatments for the prevention of heart failure.

Purpose The purpose of this study was to investigate the effect of lateral meniscal posterior root avulsions combined with intact meniscofemoral ligaments (MFLs), deficient MFLs, anterior cruciate ligament (ACL) tears and reconstructions, and root repairs using an established tibiofemoral contact mechanics testing protocol. Methods Ten fresh-frozen cadaveric knees were tested with six knee conditions (1: intact; 2: lateral meniscal posterior root avulsion; 3: root avulsion and deficient MFLs; 4: condition 3 with ACL tear; 5: condition 4 with ACL reconstruction; 6: ACL reconstruction with root repair) at five flexion angles (0°, 30°, 45°, 60°, and 90°), under a 1000-N axial load. Contact area and pressure were measured with Tekscan sensors. Results Compared to the intact state, condition 2 did not significantly change lateral compartment contact area or pressure. Changes in contact mechanics were greater at increased flexion angles; for condition 3 at 0° and 90°, contact area decreased 37 and 52 % [95 % CI (21–53) and (39–66), respectively] and mean contact pressure increased 55 and 87 % [95 % CI (33–76) and (59–114), respectively]. Root repair with ACL reconstruction was not significantly different from the intact state. Conclusions The MFLs protect the lateral compartment from changes in contact mechanics in the setting of a lateral meniscal posterior root avulsion, whereas a combination of lateral meniscal root avulsion and deficient MFLs leads to significant changes. Concurrent ACL reconstruction and lateral meniscal root repair restore mean contact pressure and area to the intact state and are recommended in this combined injury to prevent or slow the development of lateral compartment arthritis.

Purpose Limited objective data exist detailing the quantitative anatomy of the individual bundles of the proximal tibiofibular joint and their relation to surgically pertinent osseous landmarks. The purpose of this study was to qualitatively and quantitatively describe the ligamentous anatomy of the proximal tibiofibular joint and its relation to relevant bony landmarks. Methods Ten non-paired, fresh-frozen cadaveric knee specimens were dissected to identify the proximal tibiofibular joint ligament bundles. Pertinent bony landmarks were identified and served as reference points for the tibial and fibular attachments for each bundle. Ligament bundle footprints, lengths and orientations were measured using a 3D coordinate measuring device. Results Up to four bundles were identified anteriorly and up to three bundles posteriorly. The inferior bundle was identified anteriorly and posteriorly in 60% and 20% of the cases, respectively. For the anterior complex, the centres of the tibial attachments were a mean distance of 12.5 mm (95% CI [10.7, 14.3]) and 25.3 mm (95% CI [21.6, 29.0]) from the tibial plateau for the superior and inferior bundles, respectively. The centres of the fibular attachments were 11.3 mm (95% CI [7.4, 15.1]) and 27.0 mm (95% CI [24.0, 30.0]) from the apex of the fibular styloid for the superior and inferior bundles, respectively. For the bundles of the posterior complex, the centres of the tibial attachments were 13.4 mm (95% CI [11.6, 15.2]) and 38.8 mm (95% CI [31.0, 46.6]) distal to the tibial plateau for the superior and inferior bundles, respectively, and the centres of the fibular attachments were 8.0 mm (95% CI [5.8, 10.1]) and 29.3 mm (95% CI [25.5, 33.1]) from the apex of the fibular styloid for the superior and inferior bundles, respectively. In the coronal plane, the mean 2D angle between the medial to lateral knee joint axis and the axis passing through the centre of the proximal tibiofibular joint and the centre of the tibial plateau was 16.9° (95% CI [12.8, 21.0]). Conclusion The ligament bundles of the proximal tibiofibular joint were reproducibly identified between specimens in relation to surrounding bony landmarks. Up to four bundles were identified in the anterior ligament complex and up to three in the posterior complex. Variation in bundle orientation and footprint size was observed. Based on these findings, an anatomic reconstruction can be performed using surrounding reliable landmarks.

Background Patients with diabetes are at a high risk for developing cardiac dysfunction in the absence of coronary artery disease or hypertension, a condition known as diabetic cardiomyopathy. Contributing to heart failure is the presence of diabetic kidney disease. The Goto-Kakizaki (GK) rat is a non-obese, non-hypertensive model of type 2 diabetes that, like humans, shares a susceptibility locus on chromosome 10. Herein, we perform a detailed analysis of cardio-renal remodeling and response to renin angiotensin system blockade in GK rats to ascertain the validity of this model for further insights into disease pathogenesis. Methods Study 1: Male GK rats along with age matched Wistar control animals underwent longitudinal assessment of cardiac and renal function for 32 weeks (total age 48 weeks). Animals underwent regular echocardiography every 4 weeks and at sacrifice, early (~24 weeks) and late (~48 weeks) timepoints, along with pressure volume loop analysis. Histological and molecular characteristics were determined using standard techniques. Study 2: the effect of renin angiotensin system (RAS) blockade upon cardiac and renal function was assessed in GK rats. Finally, proteomic studies were conducted in vivo and in vitro to identify novel pathways involved in remodeling responses. Results GK rats developed hyperglycaemia by 12 weeks of age (p<0.01 c/w Wistar controls). Echocardiographic assessment of cardiac function demonstrated preserved systolic function by 48 weeks of age. Invasive studies demonstrated left ventricular hypertrophy, pulmonary congestion and impaired diastolic function. Renal function was preserved with evidence of hyperfiltration. Cardiac histological analysis demonstrated myocyte hypertrophy (p<0.05) with evidence of significant interstitial fibrosis (p<0.05). RT qPCR demonstrated activation of the fetal gene program, consistent with cellular hypertrophy. RAS blockade resulted in a reduction blood pressure(P<0.05) cardiac interstitial fibrosis (p<0.05) and activation of fetal gene program. No significant change on either systolic or diastolic function was observed, along with minimal impact upon renal structure or function. Proteomic studies demonstrated significant changes in proteins involved in oxidative phosp4horylation, mitochondrial dysfunction, beta-oxidation, and PI3K/Akt signalling (all p<0.05). Further, similar changes were observed in both LV samples from GK rats and H9C2 cells incubated in high glucose media. Conclusion By 48 weeks of age, the diabetic GK rat demonstrates evidence of preserved systolic function and impaired relaxation, along with cardiac hypertrophy, in the presence of hyperfiltration and elevated protein excretion. These findings suggest the GK rat demonstrates some, but not all features of diabetes induced \"cardiorenal\" syndrome. This has implications for the use of this model to assess preclinical strategies to treat cardiorenal disease.

Objectives: Reconstruction of grade-III posterior cruciate ligament (PCL) ruptures has historically been compromised by graft elongation and residual laxity. The purpose of this study was to report prospectively collected two-year outcomes and failure rates of double-bundle PCL reconstruction in a consecutive patient series with patient reported outcomes and quantitative stress radiographs. It was hypothesized that double bundle PCL reconstruction would result in improved subjective clinical outcomes, restoration of knee stability, and result in high patient satisfaction. Methods: A single surgeon consecutive series of patients that underwent double-bundle PCL reconstruction between June, 2010, and April, 2014, were followed prospectively. The technique is anatomically and biomechanically validated and utilizes two allografts (Achilles tendon for anterolateral bundle, tibialis anterior tendon for posteromedial bundle) in divergent femoral tunnels and a single tibial tunnel, each secured at the tibia at different knee angles to recreate the function of the two PCL bundles. Patient reported outcomes were collected preoperatively, and at a minimum two-year follow-up, including SF12, WOMAC, Tegner, Lysholm, and patient satisfaction. Posterior kneeling stress radiographs were obtained preoperatively and at the 6-month follow-up period. Failures were defined objectively as a difference of more than 3 mm in stress radiographs. Results: Sixty patients had greater than 2 year follow-up (mean 2.9 yrs). All subjective outcome measures improved except SF-12 mental component which was unchanged. The mean Lysholm score improved from 48 to 79. The mean WOMAC score improved from 39 to 11. The median SF-12 physical component score improved from 32 to 55. The median Tegner activity score improved from 2 to 5. The median patient satisfaction score was 8. Stress radiographs were available for 36 patients and improved from a preoperative side-to-side difference of 9.6 mm to 1.0 mm at 6 months follow-up. One failure occurred in a patient who had an 8 mm side-to-side difference at final follow-up and 18 mm pre-operatively. Conclusion: Double bundle PCL reconstruction results in improved patient reported outcomes and restoration of posterior knee stability. High patient satisfaction and low failure rates were found in this cohort of patients.

Purpose The purpose of this study was to determine the biomechanical effects of simulated immediate motion and weightbearing during rehabilitation on different double-bundle posterior cruciate ligament reconstruction (DB-PCLR) graft options. Methods Nine each of commercially prepared (allograft) Achilles tendon allografts, fresh-frozen (autograft) bone-patellar tendon-bone grafts, and fresh-frozen quadriceps tendon grafts were paired with commercially prepared anterior tibialis allografts, fresh-frozen semitendinosus grafts, and fresh-frozen semitendinosus grafts, respectively. Graft pairs were loaded to simulate early range of motion on a stationary bicycle, partial weightbearing (30 %), and full weightbearing. Results Acquired laxity (displacement, mm) between graft pairs was not significantly different during simulated early range of motion. However, during simulated partial weightbearing, the median acquired laxity of the patellar tendon/semitendinosus pair (1.06 mm) was significantly less than that of the quadriceps tendon/semitendinosus (1.50 mm, p  = 0.01) and Achilles/anterior tibialis (1.44 mm, p  = 0.003) graft pairs. During simulated full weightbearing, significantly less acquired laxity was observed for the patellar tendon/semitendinosus graft pair (2.38 mm) compared to the Achilles/anterior tibialis pair (4.85 mm, p  = 0.04), but a significant difference was not observed compared to the QT/semitendinosus graft pair (3.91 mm, n.s.). There were no significant differences in the ultimate loads between any of the graft pairs. Conclusions Simulated early range of motion and early partial weightbearing did not result in clinically significant acquired graft laxity in common graft options utilized for DB-PCLR. However, simulated full weightbearing did result in clinically significant acquired graft laxity, and therefore, early rehabilitation protocols should avoid implementing full weightbearing that could contribute to graft failure.

Translational research (TR) is a multidirectional and multidisciplinary integration of basic research, patient-oriented research and population-based research, with the long-term goal of improving human health. Unfortunately, the current scientific training system does not adequately align with the goals of TR. To address this issue, an organization called Apollo Toronto was established at the University of Toronto in Toronto, Ontario. Apollo Toronto is a medical student-run international collaborative project between the Eureka Institute for Translational Medicine and the University of Toronto (one of Eureka Institute’s partner universities), and provides a general overview of TR to interested medical and graduate students. Through local and international initiatives, the various Apollo chapters (including Apollo Toronto) aim to establish a network of trainees equipped to address systemic issues that impede the translation of an ever-growing body of scientific literature into health solutions.

Background: Vascular-derived progenitor and endothelial cell populations (CD31, CD34, CD146) are capable of multipotent differentiation at the site of injured ligamentous tissue to aid in the intrinsic healing response. Proximal ulnar collateral ligament (UCL) tears have been reported to have better healing capability when compared with distal UCL tears. Purpose: To compare the vascular composition of the proximal and distal insertions of the anterior bundle of the UCL of the elbow via known markers of endothelial and vascular-derived progenitor cells (CD31, CD34, CD146). Study Design: Descriptive laboratory study. Methods: UCLs were harvested from 10 nonpaired fresh-frozen human cadaveric elbows and transected into proximal and distal portions. Endothelial and vascular-derived progenitor cell densities were assessed with 4 staining groups: CD31 (immunohistochemistry) and CD31/α-smooth muscle actin (α-SMA), CD34/α-SMA, and CD146/α-SMA (immunofluorescence). CD31 immunohistochemistry identified endothelial progenitor cells in the UCL. Later staining of the same slides with α-SMA demonstrated the relationship of progenitor cells to the surrounding vasculature. Fluorescent staining was quantified by calculating the proportion of positively stained nuclei versus the total number of nuclei in the proximal and distal UCL. Results: CD31+ cells were present in the proximal and distal sections of all 10 UCLs. Fluorescent staining revealed no significant differences in the ratio of CD31 to total nuclei between the distal (median, 36% [range, 23%-53%]) and proximal UCL (39% [22%-56%]) (P = .432, Wilcoxon signed-rank test). Similarly, no differences were seen between CD34 distal (39% [24%-64%]) and proximal regions (46% [28%-63%]) (P = .846, Wilcoxon signed-rank test) or CD146 distal (40% [12%-65%]) and proximal regions (40% [22%-51%]) (P ≥ .999, Wilcoxon signed-rank test). Conclusion: Analysis of UCL tissues demonstrated equal distributions of vascular endothelial and vascular-derived progenitor cell markers throughout the proximal and distal UCL. Unlike that of the medial collateral ligament of the knee, the microvascular composition of the proximal and distal UCL insertions was not different, suggesting a well-vascularized ligament throughout its course. Clinical Relevance: These findings investigate one of the possible contributors to UCL healing after injury, which may provide insight into operative and nonoperative management of UCL injuries in the future. This study also indicates that reasons other than differences in progenitor cell density alone may explain the clinical healing differences seen between proximal and distal UCL tears. A better understanding of the microvascular environment and associated blood supply is warranted to understand the healing capability of the UCL.

Background The purpose of this study was to quantify the meniscal root anatomy of the New Zealand white rabbit to better understand this animal model for future in vitro and in vivo joint degeneration studies. Methods Ten non-paired fresh frozen New Zealand white rabbit knee stifle joints were carefully disarticulated for this study. Measurements were made for all bony landmarks and ligamentous structure attachment sites on the tibial plateau. The following soft tissue structures were consistently identified in the rabbit stifle joint: the anterior root attachment of the lateral meniscus, the anterior root attachment of the medial meniscus, the anterior cruciate ligament, the posterior root attachment of the medial meniscus, the ligament of Wrisberg, the posterior cruciate ligament, and the posterior meniscotibial ligament. The following bony landmarks were consistently identified: the extensor digitorum longus groove, the medial tibial eminence, the center of the tibial tuberosity, and the lateral tibial eminence. Results The center of the anterior cruciate ligament and the medial tibial eminence apex were found to be 3.4 ± 0.3 mm (2.9–3.6) and 6.1 ± 0.6 mm (5.1–7.0) respectively from the center of the medical anterior root attachment. The center of the anterior cruciate ligament and the lateral tibial eminence apex were found to be 2.1 ± 0.5 mm (1.2–2.7) and 7.0 ± 0.6 mm (6.4–8.2) respectively from the center of the lateral anterior root attachment. The center of the posterior cruciate ligament and the medial tibial eminence apex were found to be 2.0 ± 0.7 mm (0.5–2.6) and 1.8 ± 0.4 mm (1.2–2.4) respectively from the center of the medial posterior root attachment. Conclusions This study augments our understanding of the comparative anatomy of the rabbit stifle joint. This information will be useful for future biomechanical, surgical, and in vitro studies utilizing the rabbit stifle as a model for human knee joint degenerative diseases.