The Role of Copper-Induced M2 Macrophage Polarization in Protecting Cartilage Matrix in Osteoarthritis.

BACKGROUND The pathological mechanism of osteoarthritis is still unclear. The regulation of the immune microenvironment has been of growing interest in the progression and treatment of osteoarthritis. Macrophages with different phenotypes, producing different cytokines, have been linked to the mechanism of cartilage injury in osteoarthritis. Copper ions play a role in the immune response and are involved in the pathological mechanisms of osteoarthritis by affecting the metabolism of the cartilage matrix. Bioactive glass (BG) is an osteogenic material with superior biocompatibility. Here, we report on the regulatory behavior of macrophages using a copper-based composite BG material. MATERIAL AND METHODS Cu-BGC powder was prepared by sol-gel method, and scaffolds were fabricated and characterized using 3D printing. Macrophage cultures grown with Cu-BGC were examined for cell culture and proliferation. The effect of Cu-BGC on the degradation metabolism of chondrocytes, cultured in the environment of inflammatory cytokine IL-1ß, was determined. In addition, the morphology of macrophages, secretion of inflammatory cytokines, and expression of surface markers were examined. RESULTS The results show that Cu-BGC promotes macrophage proliferation at a range of concentrations and increases the secretion of anti-inflammatory cytokines while inhibiting proinflammatory cytokines. At the same time, M2-type cell surface markers are definitely expressed and the morphology of macrophages is altered. In addition, Cu-BGC inhibited the degradation metabolism of chondrocytes in the inflammatory environment induced by IL-1ß. CONCLUSIONS These results suggest that Cu-BGC induced macrophage polarization into an M2 type anti-inflammatory phenotype, and inhibition of immune injury response may play a role in delaying cartilage matrix damage in osteoarthritis.

Chondrogenic preconditioning of mesenchymal stem/stromal cells within a magnetic scaffold for osteochondral repair.

Stem cell therapy using mesenchymal stem/stromal cells (MSCs) represents a novel approach to treating severe diseases, including osteoarthritis. However, the therapeutic benefit of MSCs is highly dependent on their differentiation state, which can be regulated by many factors. Herein, three-dimensional (3D) magnetic scaffolds were successfully fabricated by incorporating magnetic nanoparticles (MNPs) into electrospun gelatin nanofibers. When positioned near a rotating magnet (f= 0.5 Hz), the magnetic scaffolds with the embedded MSCs were driven upward/downward in the culture container, which induced mechanical stimulation to MSCs due to spatial confinement and fluid flow. The extracellular matrix-mimicking scaffold and the alternating magnetic field significantly enhanced chondrogenesis instead of osteogenesis. Furthermore, the fiber topography could be tuned with different compositions of the coating layer on MNPs, and the topography had a significant impact on MSC differentiation. Selective up-regulation of chondrogenesis-related genes (COL2A1andACAN) was found for the magnetic scaffolds with citric acid-coated MNPs (CAG). In contrast, osteogenesis-related genes (RUNX2andSPARC) were selectively and significantly up-regulated for the magnetic scaffolds with polyvinylpyrrolidone-coated MNPs. Prior to implantationin vivo, chondrogenic preconditioning of MSCs within the CAG scaffolds under a dynamic magnetic field resulted in superior osteochondral repair. Hence, the magnetic scaffolds together with an in-house rotating magnet device could be a novel platform to initiate multiple stimuli on stem cell differentiation for effective repair of osteochondral defects.

Enhanced recovery after surgery protocols in total knee arthroplasty via midvastus approach: a randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols were rapidly adopted in many surgeries such as fast-track arthroplasty. The study aimed to investigate the impact of ERAS protocols on the clinical effect of total knee arthroplasty (TKA) via the midvastus approach. METHODS: A total of 69 patients who underwent primary unilateral TKA via the midvastus approach from October 2018 to June 2019 were enrolled and randomly divided into two groups: ERAS group and Control group. The ERAS protocols were adopted for the ERAS group and consisted of pure juice drinking 2 h before the surgery, optimization of the preoperative anesthesia plan, phased use of tourniquets, and the use of tranexamic acid as well as a drug cocktail. The operative time, first postoperative walking time, first straight leg elevation time, postoperative hospitalization time, visual analogue scale score (VAS score), Hospital for Special Surgery score (HSS score), conventional Knee Society score (KSS), and knee range of motion (ROM) were used to assess the clinical effects in the two groups. All the included patients were followed up for 12 months. RESULTS: There were no significant differences in the basic demographic information and operation time between the ERAS and Control groups (P > 0.05). The first postoperative walking time (2.11 ± 0.11 h) and first postoperative straight leg elevation time (6.14 ± 1.73 h) in the ERAS group were significantly earlier than those in the Control group (P < 0.001) and the postoperative hospitalization time was significantly shorter (3.11 ± 0.32 days). The postoperative mean VAS scores in both groups were significantly reduced compared with those before surgery (P < 0.001). The VAS scores for the ERAS group were significantly lower than those for the Control group at 1, 2, and 7 days after surgery (P < 0.001). The mean HSS scores, KSS, and knee ROM were significantly increased in both the ERAS and Control groups at 1, 3, 6, and 12 months after surgery (P < 0.001). In addition, the HSS scores, KSS, and knee ROM in the ERAS group were significantly higher than those in the Control group at 1 month after surgery (P < 0.001). CONCLUSIONS: ERAS protocols improved the clinical effects of TKA via the midvastus approach, facilitating early out-of-bed activity and comfortable postoperative rehabilitation exercise, and further increasing patient satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04873544 .

3D printing of Haversian bone-mimicking scaffolds for multicellular delivery in bone regeneration.

The integration of structure and function for tissue engineering scaffolds is of great importance in mimicking native bone tissue. However, the complexity of hierarchical structures, the requirement for mechanical properties, and the diversity of bone resident cells are the major challenges in constructing biomimetic bone tissue engineering scaffolds. Herein, a Haversian bone-mimicking scaffold with integrated hierarchical Haversian bone structure was successfully prepared via digital laser processing (DLP)-based 3D printing. The compressive strength and porosity of scaffolds could be well controlled by altering the parameters of the Haversian bone-mimicking structure. The Haversian bone-mimicking scaffolds showed great potential for multicellular delivery by inducing osteogenic, angiogenic, and neurogenic differentiation in vitro and accelerated the ingrowth of blood vessels and new bone formation in vivo. The work offers a new strategy for designing structured and functionalized biomaterials through mimicking native complex bone tissue for tissue regeneration.

Three-Dimensional-Printed Bioceramic Scaffolds with Osteogenic Activity for Simultaneous Photo/Magnetothermal Therapy of Bone Tumors.

For the postoperative treatment of bone cancer, biomaterials should possess an antitumor effect and simultaneous repair ability of bone defects. Compared with single photothermal treatment or magnetothermal treatment, photo/magnetothermal joint treatment represents a more high-efficient strategy to kill tumor cells. In this work, a 3D-printed bioceramic scaffold with a photo/magnetothermal effect was successfully designed and fabricated, which exhibited the function of killing tumor cells and excellent osteogenic bioactivity, via incorporating an Fe element into akermanite (AKT) bioceramics. After doping with ferric elements, the AKT scaffolds possessed significantly enhanced compressive strength and desirable ferromagnetic property. The ferric elements endowed the AKT scaffolds with excellent photo/magnetothermal effects, and hence the scaffolds could efficiently kill tumor cells in vitro under mild laser power density and magnetic field. In addition, the Fe-doped AKT bioceramic scaffolds significantly promoted cell proliferation and osteogenic differentiation of rabbit bone mesenchymal stem cells as compared with the original AKT scaffolds without Fe elements. The results suggest that Fe-doped bioceramic scaffolds with both photo/magnetothermal effect and in vitro osteogenic bioactivity could be a promising biomaterial for the synergistic therapy of bone cancers.