Osteosarcoma remains a worldwide concern due to the poor effectiveness of available therapies in the clinic. Therefore, it is necessary to find a safe and effective therapy to realize the complete resection of osteosarcoma and reconstruction of the bone defect. Magnetic hyperthermia based on magnetic nanoparticles can kill tumor cells by raising the temperature without causing the side effects of conventional cancer treatments. This research aims to design a high-performance magnetic hydrogel composed of gelatin methacrylate and highly magnetic cobalt ferrite (CFO) nanoparticles for osteosarcoma treatment. Specifically, CFO is surface functionalized with methacrylate groups (MeCFO). The surface modified CFO has good biocompatibility and stable solution dispersion ability. Afterward, MeCFO nanoparticles are incorporated into GelMA to fabricate a three-dimensional (3D) printable MeCFO/GelMA magnetic hydrogel and then photocross-linked by UV radiation. MeCFO/GelMA hydrogel has high porosity and swelling ability, indicating that the hydrogel possesses more space and good hydrophily for cell survival. The rheological results showed that the hydrogel has shear thinning property, which is suitable as a bioprinting ink to produce desired structures by a 3D printer. Furthermore, 50 μg/mL MeCFO not only decreases the cell activity of osteosarcoma cells but also promotes the osteogenic differentiation of mBMSCs. The results of the CCK-8 assay and live/dead staining showed that MeCFO/GelMA hydrogel had good cytocompatibility. These results indicated that MeCFO/GelMA hydrogel with potential antitumor and bone reconstruction functions is a promising therapeutic strategy after osteosarcoma resection.

The aim of this study was to assess inflammatory cytokines levels in synovial fluid (SF) before and after electroacupuncture (EA) treatment and to explore whether these biomarkers are associated with function of rotator cuff tear (RCT) patients. We recruited 54 patients with RCT and separated them into an EA group and a control group. The SF biomarker levels were detected at baseline and at 6-week and 6-month follow-up. The symptomatic severity was evaluated by visual analog scale (VAS), Constant-Murley score, and American Shoulder and Elbow Surgeons score (ASES). We also investigated the correlation between symptomatic severity and biomarker levels in SF of the shoulder joint. The reductions in VAS and improved functional score (ASES and Constant-Murley score) were significantly different between the 2 groups, and SF biomarker concentrations were significantly lower in the EA group. IL-1β levels were significantly negatively correlated with Constant-Murley score (r=−0.73, P=0.04) and ASES score (r=−0.59, P<0.001) and positively correlated with VAS scores (r=0.81, P=0.004). IL-6 levels were significantly negatively correlated with Constant-Murley score (r=−0.67, P=0.03) and positively correlated with VAS score (r=0.7, P=0.01). MMP-1 levels were significantly negatively correlated with ASES score (r=−0.57, P<0.001). The biomarkers in SF were directly associated with shoulder pain and shoulder function in rotator cuff tear. EA, as a safe and effective conservative therapy, obviously decreased the level of inflammatory cytokines in RCT patients, accompanied by a reduction in shoulder pain and improved function.

Osteoarthritis (OA) is a prevalent chronic disease, characterized by chronic inflammation and cartilage degradation. This study aims to deepen the understanding of OA's pathophysiology and to develop novel therapeutic strategies. Our study underscores the pivotal role of Epiphycan (EPYC) and the IL-17 signaling pathway in OA. EPYC, an essential extracellular matrix constituent, has been found to exhibit a positive correlation with the severity of OA. We have discovered that EPYC modulates the activation of the IL-17 signaling pathway within chondrocytes by regulating the interaction between IL-17A and its receptor, IL-17RA. This regulatory mechanism underscores the intricate interplay between the extracellular matrix and immune signaling in the pathogenesis of OA Another finding of our study is the therapeutic effectiveness of protocatechualdehyde (PAH) in OA. PAH significantly reduces chondrocyte hypertrophy and supports cartilage tissue recovery.by targets EPYC. To reduce the side effects of orally administered PAH and maintain its effective drug concentration, we have developed a decellularized matrix hydrogel loaded with PAH for intra-articular injection. This novel drug delivery system is advantageous in minimizing drug-related side effects and ensuring sustained release PAH within the joint cavity.

Introduction: During the healing process, the functional gradient attachment of the rotator cuff (RC) tendon-bone interface fails to regenerate, which severely impedes load transfer and stress dissipation, thereby increasing the risk of retears. As a result, the treatment of rotator cuff tears remains a significant clinical challenge.Methods: In this study, a dual-crosslinked hyaluronic acid/polyethylene glycol (HA/PEG) hydrogel scaffold was synthesized using hyaluronic acid and polyethylene glycol as base materials. Manganese-doped mesoporous silica nanoparticles (Mn-MSN) were incorporated into the hydrogel system to fabricate a manganese-based mesoporous silica nanoparticle-loaded dual-crosslinked hydrogel (Mn-MSN@Gel). The physicochemical properties of Mn-MSN@Gel, including porosity, elemental distribution, mechanical properties, biodegradability, and biocompatibility, were systematically characterized. The ion release profiles of Si⁴⁺ and Mn⁴⁺ were evaluated to assess sustained delivery. Rheological properties and self-healing capabilities were examined to determine injectability and in vivo stability. In vitro, the effects of Mn-MSN@Gel on cell migration, proliferation, and differentiation were assessed using rat bone marrow mesenchymal stem cells (rat-BMSCs) and tendon-derived stem cells (rat-TDSCs). The expression of osteogenic, tenogenic, oxidative stress-related, and inflammatory cytokine genes was analyzed. In vivo, a rat rotator cuff repair model was established to evaluate the biomechanical properties and tissue regeneration at the tendon-bone interface (TBI) following Mn-MSN@Gel injection.Results: Characterization demonstrated that Mn-MSN@Gel possesses a porous three-dimensional structure with uniform distribution of silicon, oxygen, and manganese elements, enabling sustained and slow release of Si⁴⁺ and Mn⁴⁺ ions. Additionally, the composite material exhibited excellent mechanical properties, biodegradability, and biocompatibility, while promoting cell migration/proliferation and accelerating regeneration of the tendon-bone interface. Mn-MSN@Gel enhanced the expression of osteogenic differentiation genes (Runx2, Alp, Sox9) in rat-BMSCs, upregulated tenogenic differentiation markers (Scx, Tnmd, Col3a1), and downregulated Mmp3 expression in rat-TDSCs. Furthermore, Mn-MSN@Gel modulated genes related to oxidative stress (Nrf2, Gpx4, Sod2) and inflammatory cytokines (IL-6, IL-10, Tnf-α), exhibiting anti-inflammatory effects and alleviating oxidative stress damage. In the rat rotator cuff repair model, Mn-MSN@Gel injection significantly improved postoperative biomechanical properties and promoted tissue regeneration at the TBI.Discussion: The self-healing and injectable properties of Mn-MSN@Gel ensure precise delivery and stable integration in vivo. By combining mechanical support with sustained release of bioactive ions, Mn-MSN@Gel provides a comprehensive therapeutic strategy for regenerative repair of the tendon-bone interface. Its biocompatibility and bioactivity facilitate cell recruitment, migration, and lineage-specific differentiation, which are crucial for reconstructing the functional gradient structure of the TBI. The anti-inflammatory and antioxidant effects further contribute to a favorable healing microenvironment. Overall, these findings indicate that Mn-MSN@Gel is a foundational biomaterial with significant therapeutic potential for enhancing structural regeneration and functional recovery of the TBI following rotator cuff injury.

Objective: To explore the effect of diabetes mellitus (DM) on implant osseointegration of titanium screws.Methods: Sixty rats were randomly divided into a DM group and a control group (each group, n = 30). DM group rats were injected with 1% Streptozotocin solution at 65 mg/kg to establish a DM model. Titanium screws were implanted into the rats' distal femurs in both groups. The rats were sacrificed for micro‐CT scanning, micro‐indentation, biomechanical detection, confocal Raman microspectroscopy, and histological and histomorphometric analysis at 4, 8, and 12 weeks post‐implantation, respectively. Messenger RNA (mRNA) expression and protein expression of the related growth factors around the implant were analyzed using real‐time polymerase chain reaction and Western blots.Results: At 4, 8 and 12 weeks, micro‐CT scanning, hematoxylin‐eosin (HE) staining, Gieson's acid‐magenta staining, and fluorescent labeled staining showed disorder in the bone tissue arrangement, a lack of new bone tissue, poor maturity and continuity, and poor trabecular bone parameters around the implant in the DM group. At 4, 8, and 12 weeks, the interfacial bone binding rate in the DM group was significantly lower (16.2% ± 4.8%, 25.7% ± 5.7%, 42.5% ± 5.8%, respectively) than that in the control group (23.6% ± 5.2%, 40.8% ± 6.3%, 64.2% ± 7.3%, respectively; P < 0.05). At 8 and 12 weeks, the elastic modulus (17.0 ± 1.8 and 15.1 ± 1.5 GPa, respectively) and trabecular bone hardness (571 ± 39 and 401 ± 37 MPa, respectively) in the DM group were significantly lower than the elastic modulus (23.4 ± 2.3 and 23.8 ± 1.8 GPa, respectively) and trabecular bone hardness (711 ± 45 and 719 ± 46 MPa, respectively) in the control group (P < 0.05). The maximum load required for the prosthesis pull‐out experiment in the DM group at 4, 8, and 12 weeks (55.14 ± 6.74 N, 73.34 ± 8.43 N, and 83.45 ± 8.32 N, respectively) was significantly lower than that in the control group (77.45 ± 7.48 N, 93.28 ± 8.29 N, and 123.62 ± 9.43 N, respectively, P < 0.05). At 8 and 12 weeks, the mineral‐to‐collagen ratio in the DM group (6.56 % ± 1.35% and 4.45%± 1.25%, respectively) was significantly higher than that in the control group (5.31% ± 1.42% and 3.62% ± 1.33%, respectively, P < 0.05). At 12 weeks, mRNA and protein expression levels of bone morphogenetic protein 2, transforming growth factor‐β1, vascular endothelial growth factor, osteopontin, osteocalcin, and runt‐related transcription factor 2 in the DM group were significantly lower than that in the control group.Conclusions: DM can negatively affect bone osseointegration, manifesting as disorder in bone tissue arrangement around the implant, a lack of new bone tissue, poor maturity and continuity, poor trabecular bone parameters and lower expression of the related growth factors.