SummaryThree-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.

Objective: To explore the effects of Mg 2þ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg 2þ in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT þ PMM). Design: Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl 2 (20 mmol/L) in vitro. A rat OA model was established by ACLT þ PMM surgery in 450e500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl 2 (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl 2 was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction. Results: The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg 2þ in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg 2þ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT þ PMM rats were significantly improved by intra-articular injections of Mg 2þ (0.5 mol/ L). Immunohistochemical analysis also showed the regulatory effects of Mg 2þ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results. Conclusion: Intra-articular injections of Mg 2þ at 0.5 mol/L attenuate the progression of OA in the ACLT þ PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.

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.

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.

SummaryBackground/objectiveOxidative 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.MethodsTwelve 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.ResultsGait 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).ConclusionIntra-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.