Directionalities of magnetic fields and topographic scaffolds synergise to enhance MSC chondrogenesis.

Mesenchymal stem cell (MSC) chondrogenesis is modulated by diverse biophysical cues. We have previously shown that brief, low-amplitude pulsed electromagnetic fields (PEMFs) differentially enhance MSC chondrogenesis in scaffold-free pellet cultures versus conventional tissue culture plastic (TCP), indicating an interplay between magnetism and micromechanical environment. Here, we examined the influence of PEMF directionality over the chondrogenic differentiation of MSCs laden on electrospun fibrous scaffolds of either random (RND) or aligned (ALN) orientations. Correlating MSCs' chondrogenic outcome to pFAK activation and YAP localisation, MSCs on the RND scaffolds experienced the least amount of resting mechanical stress and underwent greatest chondrogenic differentiation in response to brief PEMF exposure (10 min at 1 mT) perpendicular to the dominant plane of the scaffolds (Z-directed). By contrast, in MSC-impregnated RND scaffolds, greatest mitochondrial respiration resulted from X-directed PEMF exposure (parallel to the scaffold plane), and was associated with curtailed chondrogenesis. MSCs on TCP or the ALN scaffolds exhibited greater resting mechanical stress and accordingly, were unresponsive, or negatively responsive, to PEMF exposure from all directions. The efficacy of PEMF-induced MSC chondrogenesis is hence regulated in a multifaceted manner involving focal adhesion dynamics, as well as mitochondrial responses, culminating in a final cellular response. The combined contributions of micromechanical environment and magnetic field orientation hence will need to be considered when designing magnetic exposure paradigms.

Temporal activation of ß-catenin signaling in the chondrogenic process of mesenchymal stem cells affects the phenotype of the cartilage generated.

Adult mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering. In vitro predifferentiation of MSCs has been explored as a means to enhance MSC-based articular cartilage repair. However, there remain challenges to control and prevent the premature progression of MSC-derived chondrocytes to the hypertrophy. This study investigated the temporal effect of transforming growth factor (TGF)-ß and ß-catenin signaling co-activation during MSC chondrogenic differentiation and evaluated the influence of these predifferentiation conditions to subsequent phenotypic development of the cartilage. MSCs were differentiated in chondrogenic medium that contained either TGFß alone, TGFß with transient ß-catenin coactivation, or TGFß with continuous ß-catenin coactivation. After in vitro differentiation, the pellets were transplanted into SCID mice. Both coactivation protocols resulted in the enhancement of chondrogenic differentiation of MSCs. Compared with TGFß activation, transient coactivation of TGFß-induction with ß-catenin activation resulted in heightened hypertrophy and formed highly ossified tissues with marrow-like hematopoietic tissue in vivo. The continuous coactivation of the 2 signaling pathways, however, resulted in inhibition of progression to hypertrophy, marked by the suppression of type X collagen, Runx2, and alkaline phosphatase expression, and did not result in ossified tissue in vivo. Chondrocytes of the continuous co-activation samples secreted significantly more parathyroid hormone-related protein (PTHrP) and expressed cyclin D1. Our results suggest that temporal co-activation of the TGFß signaling pathway with ß-catenin can yield cartilage of different phenotype, represents a potential MSC predifferentiation protocol before clinical implantation, and has potential applications for the engineering of cartilage tissue.

Common lower limb sport-related overuse injuries in young athletes.

INTRODUCTION: Sports injuries in children and adolescent present a unique challenge to the physician. They are often seen for clinical conditions unique to their age group. This paper highlights the epidemiological aspect of sports-related overuse injuries in this age group. MATERIALS AND METHODS: This retrospective study reviewed all the paediatric patients diagnosed with overuses injuries during a 5 years and 7 months period. The overuse injuries were anterior superior iliac spine avulsion fracture, Osgood-Schlatter disease, Sinding-Larson-Johansson disease, osteochondritis dissecan and Sever's disease. We reviewed the literature and attempted to give an overview for each condition and the anatomical differences that contributed to their occurrence in this age group. RESULTS: A total of 506 cases of the overuse injuries were seen during the study period. Seventy-three per cent were male patients. The knee joint was the commonest affected joint while the hip was the least affected joint. The mean age at diagnosis was younger in female compared to male for all conditions except in Sinding-Larson Johansson syndrome. Female was diagnosed at a mean age of 11.7 years while male at 10.8 years. Osgood-Schlatter disease was the commonest among the overuse injuries. There was no discernible racial predilection for these conditions except in the patients with anterior superior iliac spine avulsion. CONCLUSIONS: Overuse injuries are not uncommon in children and adolescent. An adequate understanding of the anatomy of the sports the children participated in as well as the anatomical differences between adult and children may assist the primary care providers better meet parents' and coaches' expectations.