Persistent quadriceps muscle atrophy after anterior cruciate ligament reconstruction is associated with alterations in exercise-induced myokine production.

Purpose: Persistent quadriceps muscle atrophy is observed in a subset of patients following anterior cruciate ligament reconstruction (ACLR) despite the completion of comprehensive rehabilitation. Critically, quadriceps muscle atrophy correlates with muscle weakness and quadriceps strength deficits. The aim of this study was to examine the effect of resistance exercise on myokine levels and muscle atrophy status in ACLR patients with persistent quadriceps muscle atrophy. Methods: Sixteen participants between the ages of 18-39 with a Tegner score of >6 and who had undergone ACLR with hamstring graft were recruited for the study. Quadriceps muscle thicknesses were ascertained by ultrasonography and isokinetic strength assessments were made prior to commencing a single bout of resistance exercise training (RET). Blood samples were taken before and after RET and assayed for myokine expression. Self-reported activity level and knee function questionnaires were completed and recorded. Results: Clustering by quadriceps muscle size measurements created a non-atrophy group of 9 subjects and an atrophy group of 7 subjects. There were no significant between-group differences in anthropometric measurements, time post operation and knee function questionnaires, but the atrophic group comprised of patients with lower pre-injury sporting levels. The atrophy group exhibited significant lower side-to-side muscle thickness ratios and a decreasing trend in quadriceps strength deficits. Serum brain-derived neurotrophic factor (BDNF) was up-regulated in response to RET in non-atrophy group, but a negative fold change was detected in the atrophy group. Conclusion: The dysregulation in myokines plays an important role in patients failing to regain muscle mass after ACLR leading to persistent quadriceps muscle atrophy, which may potentiate greater strength deficits and poor functional recovery.

Intra-Articular Delivery of Quercetin Using Thermosensitive Hydrogel Attenuate Cartilage Degradation in an Osteoarthritis Rat Model.

OBJECTIVE: Quercetin (Que), a bioflavonoid, is both anti-inflammatory and antioxidative. Que has been used as an oral supplement for osteoarthritis (OA) with inconsistent findings because of its low bioavailability. We encapsulated Que in a mPEG-polypeptide thermogel to prolong its bioactivity. The efficacy of this formulation was evaluated in a posttraumatic OA rat model. DESIGN: Methoxy-poly(ethylene glycol)-l-poly(alanine) (mPEG-PA) polymer was synthesized and characterized in terms of cytotoxicity and release kinetics in vitro. At 12 weeks old, Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT). At 24 weeks post-operation, rats received either an intra-articular (IA) injection of saline, hydrogel, or hydrogel with Que (50 or 500 µg). Gait analysis was performed at pre-ACLT, pre-treatment, and at 4, 8, and 12 weeks post-treatment. At 12 weeks post-treatment, knee joints were collected for histopathological evaluation. RESULTS: In vitro studies showed that chondrocytes were viable after 72 hours of incubation with mPEG-PA, and the release of Que could be sustained for >28 days. Among all OA rats, the limb idleness index (LII) were significantly increased at 24 weeks post-ACLT. Rats that received hydrogel with Que (50 µg) showed the most reduction in LII at both 4 and 8 weeks post-treatment. The Osteoarthritis Research Society International score of rats received hydrogel with Que (50 µg) was significantly lower than the control group. All rats suffered from low-grade synovitis (Krenn score: 2-4). CONCLUSION: This study suggests that a sustained delivery of Que (50 µg) could provide symptom relief and also delay the progression of OA in the knee.

Intra-articular injection of an antioxidant formulation did not improve structural degeneration in a rat model of post-traumatic osteoarthritis.

BACKGROUND/OBJECTIVE: Oxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model. METHODS: Twelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 µL of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks (n = 5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment. RESULTS: Gait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time (p = 0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group (p = 0.047, Mann-Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups (p > 0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20-26) and 20 (range, 9-26), respectively (p = 0.382, Mann-Whitney U test). CONCLUSION: Intra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.

From the printer: Potential of three-dimensional printing for orthopaedic applications.

Three-dimensional (3D) printers can create complex structures based on digital models. The combination of medical diagnostic imaging with 3D printing has great potential in day-to-day clinics for patient-specific solutions and applications. In the musculoskeletal system, 3D printing is used to create custom-made implants, patient-specific instrumentation, and to regenerate tissues, in particular bone and cartilage. The major limiting factors for bioprinting include the lack of printing techniques with optimal printing resolution and materials with ideal mechanical strengths while maintaining cellular functionality. Before "tissues from the printer" can be widely applied, further research and development on improving and optimising printing techniques and biomaterials, and knowledge on the development of printed constructs into living tissues, is essential for future clinical application of this technology.

Second harmonic correlation spectroscopy: a method for determining surface binding kinetics and thermodynamics.

These studies describe the implementation of second harmonic correlation spectroscopy (SHCS) to measure the adsorption and desorption kinetics of molecular species associated with a surface. Specifically, the local fluctuations of the measured second harmonic (SH) signal were used to determine the binding kinetics and thermodynamics of (S)-(+)-1,1'-bi-2-napthol SBN intercalation into a 1,2-dioleoyl-sn-glycero-3-phosphocoline (DOPC) bilayer. In order to determine the adsorption and desorption rates, the SH signal was collected above saturation concentration at steady-state equilibrium as a function of time. The autocorrelated SH signal was then fit to a correlation model developed for molecules binding at a surface when there is no contribution from molecules in solution. The measured adsorption rate for SBN to DOPC was 2.7 ± 0.2 × 10(3) s(-1) M(-1) and the desorption rate was 9 ± 4 × 10(-4) s(-1). The kinetic rates as well as the calculated equilibrium binding constant, 3.0 ± 1.3 × 10(6) M(-1) obtained from SHCS were compared with those obtained from a conventional binding isotherm and found to be statistically consistent. The primary advantage of using SHCS is both the absorption and desorption rates were determined in the same experiment using only a single bulk concentration of SBN. The results of these studies demonstrate that SHCS can be used to provide accurate kinetic and thermodynamic binding data in a label-free manner in lieu of conventional isotherm studies, especially where time and analyte are scarce.

Assembly of lipid bilayers on silica and modified silica colloids by reconstitution of dried lipid films.

A method is presented for the assembly of lipid bilayers on silica colloids via reconstitution of dried lipid films solvent-cast from chloroform within packed beds of colloids ranging from 100 nm to 10 µm in diameter. Rapid solvent evaporation from the packed bed void volume results in uniform distribution of dried lipid throughout the colloidal bed. Fluorescence measurements indicate that significant, if not quantitative, retention of DOPC or DPPC films cast between sub-bilayer and multilayer quantities occurs when the colloids are redispersed in aqueous solution. Phospholipid bilayers assembled in this manner are shown to effectively passivate the surface of 250 nm colloids to nonspecific adsorption of bovine serum albumin. The method is shown to be capable of preparing supported bilayers on colloid surfaces that do not generally support vesicle fusion such as poly(ethylene glycol) (PEG) modified silica colloids. Bilayers of lipids that have not been reported to self-assemble by vesicle fusion, including gel-phase lipids and single-chain diacetylene amphiphiles, can also be formed by this method. The utility of the solid-core support is demonstrated by the facile assembly of supported lipid bilayers within fused silica capillaries to generate materials that are potentially suitable for the analysis of membrane interactions in a microchannel format.