Implant‐associated infections (IAIs) are a common cause of orthopedic surgery failure due to microbial biofilm‐induced antibiotic‐resistance and innate immune inactivation. Thus, the destruction of microbial biofilm plays a key role in reducing IAIs. Herein, first, a magneto‐based synergetic therapy (MST) is proposed and demonstrated against IAIs based on biofilm destruction. Under an alternating magnetic field (AMF), CoFe2O4@MnFe2O4 nanoparticles (MNPs), with a rather strong magnetic hyperthermal capacity, can generate sufficient thermal effect to cause dense biofilm dispersal. Loosened biofilms provide channels through which nitrosothiol‐coated MNPs (MNP‐SNOs) can penetrate. Subsequently, thermosensitive nitrosothiols rapidly release nitric oxide (NO) inside biofilms, thus efficiently killing sessile bacteria under the magnetothermal effect of MNPs. More importantly, MNP‐SNOs can trigger macrophage‐related immunity to prevent the relapse of IAIs by exposing the infected foci to a consistent innate immunomodulatory effect. The notable anti‐infection effect of this nanoplatform is also confirmed in a rat IAI model. This work presents the promising potential of combining magnetothermal therapy with immunotherapy, for the effective and durable control and elimination of IAIs.
Background: Femoral stem of titanium alloy has been widely used for hip arthroplasty with considerable efficacy; however, the application of this implant in patients with osteoporosis is limited due to excessive bone resorption. Macrophages participate in the regulation of inflammatory response and have been a topic of increasing research interest in implant field. However, few study has explored the link between macrophage polarization and osteogenic–osteoclastic differentiation. The present study aims to develop a novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold with enhanced osteoporotic osseointegration through immunotherapy.Method: To improve the osteointegration under osteoporosis, we developed a hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold (PT). Biomimetic extracellular matrix (ECM) was constructed inside the interconnected pores of PT in micro-scale. And in nano-scale, a drug cargo icariin@Mg-MOF-74 (ICA@MOF) was wrapped in ECM-like structure that can control release of icariin and Mg2+.Results: In this novel hierarchical biofunctionalized 3D-printed porous Ti6Al4V scaffold, the macroporous structure provides mechanical support, the microporous structure facilitates cell adhesion and enhances biocompatibility, and the nanostructure plays a biological effect. We also demonstrate the formation of abundant new bone at peripheral and internal sites after intramedullary implantation of the biofunctionalized PT into the distal femur in osteoporotic rats. We further find that the controlled-release of icariin and Mg2+from the biofunctionalized PT can significantly improve the polarization of M0 macrophages to M2-type by inhibiting notch1 signaling pathway and induce the secretion of anti-inflammatory cytokines; thus, it significantly ameliorates bone metabolism, which contributes to improving the osseointegration between the PT and osteoporotic bone.Conclusion: The therapeutic potential of hierarchical PT implants containing controlled release system are effective in geriatric orthopaedic osseointegration.Graphical
Vertical femoral neck fractures in patients younger than 65 years of age often require hip‐conserving surgeries. However, traditional fixation strategies using three parallel cannulated screws often fail in such patients due to an unfavorable biomechanical environment. This study compared different cannulated screw fixation techniques in patients via patient‐specific finite element analysis with linear tetrahedral (C3D4) elements. Forty vertical femoral neck fracture models were created based on computed tomography images obtained from eight healthy participants. Five different fixation strategies: alpha, buttress, rhomboid, inverted triangle, and triangle were assessed in walking status. Biomechanical parameters including stiffness, interfragmentary motion in two directions (detachment and shearing), compression force, and maximal implant stress were evaluated. The mean relative coefficient of strain distribution between the finite element analysis and experiment was from 0.78 to 0.94. Stiffness was highest (p < .05) in the buttress group (923.1 N/mm), while interfragmentary motion was lowest (p < .05) in the alpha group. Maximal stress was highest (p < .05) in the buttress group and lowest in the alpha group. Shearing values were significantly lower in the alpha group than in the rhomboid group (p = .004). Moreover, Shearing values were significantly higher (p = .027), while detachment values were significantly lower (p = .027), in the inverted triangle than in the triangle group. Clinical significance: Our results suggest that alpha fixation is the most reliable and biomechanically efficient strategy for young patients with vertical femoral neck fractures. Regular and inverted triangular fixation strategies may be suitable for fractures of different skeletal constructions due to antidetachment/shearing abilities.