Functional tissue engineering of ligament healing

Ligaments and tendons are dense connective tissues that are important in transmitting forces and facilitate joint articulation in the musculoskeletal system. Their injury frequency is high especially for those that are functional important, like the anterior cruciate ligament (ACL) and medial collateral ligament (MCL) of the knee as well as the glenohumeral ligaments and the rotator cuff tendons of the shoulder. Because the healing responses are different in these ligaments and tendons after injury, the consequences and treatments are tissue- and site-specific. In this review, we will elaborate on the injuries of the knee ligaments as well as using functional tissue engineering (FTE) approaches to improve their healing. Specifically, the ACL of knee has limited capability to heal, and results of non-surgical management of its midsubstance rupture have been poor. Consequently, surgical reconstruction of the ACL is regularly performed to gain knee stability. However, the long-term results are not satisfactory besides the numerous complications accompanied with the surgeries. With the rapid development of FTE, there is a renewed interest in revisiting ACL healing. Approaches such as using growth factors, stem cells and scaffolds have been widely investigated. In this article, the biology of normal and healing ligaments is first reviewed, followed by a discussion on the issues related to the treatment of ACL injuries. Afterwards, current promising FTE methods are presented for the treatment of ligament injuries, including the use of growth factors, gene delivery, and cell therapy with a particular emphasis on the use of ECM bioscaffolds. The challenging areas are listed in the future direction that suggests where collection of energy could be placed in order to restore the injured ligaments and tendons structurally and functionally

Extensional flow at low Reynolds number with surface tension

The extensional flow and break-up of fluids has long interested many authors. A slender viscous fluid drop falling under gravity from beneath a horizontal surface is examined. After reviewing previous work which has neglected surface tension, a one-dimensional model which describes the evolution of such a drop, beginning with a prescribed initial drop shape and including the effects of gravity and surface tension, is investigated. Inertial effects are ignored due to the high viscosity of the fluid. Particular attention is paid to the boundary condition near the bottom of the drop where the one-dimensional approximation is no longer valid. The evolving shape of the drop is calculated up to a crisis time at which the cross-sectional area at some location goes to zero. Results are compared with those obtained when surface tension is neglected. Near to the crisis time, as the Reynolds number increases and inertia becomes non-negligible, the model assumptions are invalid so that the model does not describe actual pinch-off of a fluid drop.Y. M. Stokes, B. H. Bradshaw-Hajek and E. O. Tuc

Genomic Analysis of Colombian Leishmania panamensis strains with different level of virulence

Abstract The establishment of Leishmania infection in mammalian hosts and the subsequent manifestation of clinical symptoms require internalization into macrophages, immune evasion and parasite survival and replication. Although many of the genes involved in these processes have been described, the genetic and genomic variability associated to differences in virulence is largely unknown. Here we present the genomic variation of four Leishmania (Viannia) panamensis strains exhibiting different levels of virulence in BALB/c mice and its application to predict novel genes related to virulence. De novo DNA sequencing and assembly of the most virulent strain allowed comparative genomics analysis with sequenced L. (Viannia) panamensis and L. (Viannia) braziliensis strains, and showed important variations at intra and interspecific levels. Moreover, the mutation detection and a CNV search revealed both base and structural genomic variation within the species. Interestingly, we found differences in the copy number and protein diversity of some genes previously related to virulence. Several machine-learning approaches were applied to combine previous knowledge with features derived from genomic variation and predict a curated set of 66 novel genes related to virulence. These genes can be prioritized for validation experiments and could potentially become promising drug and immune targets for the development of novel prophylactic and therapeutic interventions

Hemodynamics: An Introduction

International audienceThe cardiovascular transport circuit is involved in both mass and heat transfer. It carries blood cells as well as oxygen and nutrients to cells of the body’s organs through the perfusing systemic arterial bed and wastes produced by working cells to their final destinations through draining veins. Blood flows throughout the body in the vasculature due to a pressure difference between the ventricular outlet and atrial inlet. Blood is propelled in the systemic and pulmonary circulation by the synchronized action of the left and right apposed cardiac pumps, respectively. Hemodynamics is related to the flow features in the heart and blood vessels, in normal and pathological conditions, in particular the pressure–flow relations and transport of substances by blood to given target organs. It can be required in therapy planning and optimization