Deleterious Effects of Intermittent Recombinant Parathyroid Hormone on Cartilage Formation in a Rabbit Microfracture Model: a Preliminary Study

Intermittent parathyroid hormone administration can enhance fracture healing in an animal model. Despite the success of exogenous parathyroid hormone on fracture healing and spine fusion, few studies have examined the role of parathyroid hormone on cartilage formation. We determined the effects of intermittent parathyroid hormone on cartilage formation in a rabbit microfracture model of cartilage regeneration. Twelve rabbits were divided into three equal groups: (1) microfracture alone, (2) microfracture + parathyroid hormone daily for 7 days, and (3) microfracture + parathyroid hormone for 28 days. Nonoperated contralateral knees were used as controls. The animals were sacrificed at 3 months and gross and histologic analysis was performed. The microfracture alone group demonstrated the most healing on gross and histologic analysis. Treatment with either 1 or 4 weeks of parathyroid hormone inhibited cartilage formation. Although discouraging from a cartilage repair point of view, this study suggests that the role parathyroid hormone administration has in clinical fracture healing must be examined carefully. Although parathyroid hormone is beneficial to promote healing in spine fusion and midshaft fractures, its deleterious effects on cartilage formation suggests that it may have adverse effects on the outcomes of periarticular fractures such as tibial plateau injuries that require cartilage healing for a successful clinical outcome

Fear expression is suppressed by tyrosine administration

Animal studies have demonstrated that catecholamines regulate several aspects of fear conditioning. In humans, however, pharmacological manipulations of the catecholaminergic system have been scarce, and their primary focus has been to interfering with catecholaminergic activity after fear acquisition or expression had taken place, using L-Dopa, primarily, as catecholaminergic precursor. Here, we sought to determine if putative increases in presynaptic dopamine and norepinephrine by tyrosine administered before conditioning could affect fear expression. Electrodermal activity (EDA) of 46 healthy participants (24 placebo, 22 tyrosine) was measured in a fear instructed task. Results showed that tyrosine abolished fear expression compared to placebo. Importantly, tyrosine did not affect EDA responses to the aversive stimulus (UCS) or alter participants' mood. Therefore, the effect of tyrosine on fear expression cannot be attributed to these factors. Taken together, these findings provide evidence that the catecholaminergic system influences fear expression in humans

An ex vivo continuous passive motion model in a porcine knee for assessing primary stability of cell-free collagen gel plugs

<p>Abstract</p> <p>Background</p> <p>Primary stability of cartilage repair constructs is of the utmost importance in the clinical setting but few continuous passive motion (CPM) models are available. Our study aimed to establish a novel ex vivo CPM animal model and to evaluate the required motion cycles for testing the mechanical properties of a new cell-free collagen type I gel plug (CaReS^®-1S).</p> <p>Methods</p> <p>A novel ex vivo CPM device was developed. Full-thickness cartilage defects (11 mm diameter by 6 mm deep) were created on the medial femoral condyle of porcine knee specimens. CaReS^®-1S was implanted in 16 animals and each knee underwent continuous passive motion. After 0, 2000, 4000, 6000, and 8000 motions, standardized digital pictures of the grafts were taken, focusing on the worn surfaces. The percentage of worn surface on the total CaReS^®-1S surface was evaluated with image processing software.</p> <p>Results</p> <p>Significant differences in the worn surface were recorded between 0 and 2000 motion cycles (p < 0.0001). After 2000 motion cycles, there was no significant difference. No total delamination of CaReS^®-1S with an empty defect site was recorded.</p> <p>Conclusion</p> <p>The ex vivo CPM animal model is appropriate in investigating CaReS^®-1S durability under continuous passive motion. 2000 motion cycles appear adequate to assess the primary stability of type I collagen gels used to repair focal chondral defects.</p

The subchondral bone in articular cartilage repair: current problems in the surgical management

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed

Augmenting virtual spaces: affective feedback in computer games

Computer games can be considered a form of art insomuch as they are critiqued, revered and collected for their aesthetics in addition to their ludic qualities. Perhaps most significantly, computer games incite a plethora of emotional responses in their players as a deliberate and defining mechanism. However, unlike other forms of traditional media and art, another key feature of games is their intrinsic interactivity, reliance upon technology and non-linearity. These traits make them particularly noteworthy if one wishes to consider how art forms might respond and adapt to their audience’s emotions. The field of affective computing has been developing for several decades and many of its applications have been in the analysis and modelling of emotional responses to forms of media, such as music and film. In gaming, recent developments have led to an increasing number of consumer-grade biofeedback devices which are available on the market, some of which are explicitly sold as ‘gaming controllers’, giving rise to greater opportunity for affective feedback to be incorporated. In this chapter, a review is provided of the affective gaming field. Specifically, it is proposed that these developments give rise to interesting opportunities whereby virtual environments can be augmented with player affective and contextual information. An overview is provided of affective computing fundamentals and their manifestation in developments relating specifically to games. The chapter considers the impact this biometric information has upon games players, in terms of their experience of the game and the social connections between competitors. A number of associated practical and technological challenges are highlighted along with areas for future research and development activities. It is hoped that by exploring these developments in gaming that the longer established forms of art and media might be inspired to further embrace the possibilities offered by utilising affective feedback

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

Background. Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design. A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion. This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration. Netherlands Trial Register (NTR1636)

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place