Contralateral Neck-shaft Angle Lower Than 130° Is Associated With Clinical Failure in Nongeriatric Individuals: Analysis of the National Femoral Neck Fracture Database of 1066 Patients.

BACKGROUND: Treatment of femoral neck fractures in patients who are nongeriatric (≤ 60 years) is challenging because of high failure rates. Anatomic parameters influence the biomechanical environment for fracture healing, but their associations with clinical prognosis remains unclear. QUESTIONS/PURPOSES: (1) Which anatomic parameter that is identifiable on pelvic radiographs shows a statistical correlation with a higher risk of clinical failure defined as nonunion, avascular necrosis (AVN), reoperation, and functional failure (decrease in Harris hip score reaching the minimum clinically important difference) in the screw fixation of femoral neck fractures among nongeriatric patients? (2) How does the influence of anatomic parameters on clinical prognosis manifest: directly or mediated by additional mechanisms? METHODS: This retrospective, multicenter study used a nationwide database in China. Between January 2014 and December 2020, we evaluated 1066 patients with femoral neck fractures with a median age of 53 years (interquartile range 46 to 56) and median follow-up period of 62 months. Anatomic parameters including femoral neck-shaft angle (NSA), femoral head radius, femoral neck width, femoral offset, acetabular center-edge angle, and acetabular sharp angle were variables of interest. The primary outcome was clinical failure including nonunion, AVN, reoperation, and functional failure (decrease in Harris hip score reaching the minimum clinically important difference). Risk factors for failure were first filtered using the Bayesian information criterion and then assessed with multiple regression adjusting for confounders. The mediation effect was further explored using model-based causal mediation analysis with a quasi-Bayesian Monte Carlo method. RESULTS: Of all anatomic parameters we assessed, the contralateral NSA was associated with clinical failure, after adjusting for all potential covariates and confounding variables (adjusted odds ratio 0.92 [95% confidence interval 0.89 to 0.95]; p < 0.001). The optimal threshold for the NSA was 130°, with the highest Youden index of 0.27. Patients with an NSA < 130° (41% [441 of 1066]) demonstrated an increased occurrence of nonunion (15% [68 of 441] versus 5% [33 of 625]; p < 0.001), AVN (32% [141 of 441] versus 22% [136 of 625]; p < 0.001), functional failure (25% [110 of 441] versus 15% [93 of 625]), and reoperations (28% [122 of 441] versus 13% [79 of 625]). The impact of an NSA less than 130° on clinical failure was direct and substantially mediated by the type of displaced fracture (mediation proportion: 18.7%). CONCLUSION: In our study of screw fixations for femoral neck fractures among nongeriatric patients, we identified that a contralateral NSA < 130° correlates with an increased risk of clinical failure including nonunion, AVN, functional failure, and reoperation. The effect is either direct or mediated through displaced fracture types. This is important for surgeons in order to recognize the elevated rate of clinical failure and nature of the challenging biomechanical environment, which should guide them in refining surgical details and selecting appropriate fixation and rehabilitation plans. Approaches to managing these fractures require further validation with large-scale clinical trials. LEVEL OF EVIDENCE: Level III, prognostic study.

Conjugated Polymer Heteroatom Engineering Enables High Detectivity Symmetric Ambipolar Phototransistors.

Solution-processed high-performing ambipolar organic phototransistors (OPTs) can enable low-cost integrated circuits. Here, a heteroatom engineering approach to modify the electron affinity of a low band gap diketopyrrolopyrole (DPP) co-polymer, resulting in well-balanced charge transport, a more preferential edge-on orientation and higher crystallinity, is demonstrated. Changing the comonomer heteroatom from sulfur (benzothiadiazole (BT)) to oxygen (benzooxadiazole (BO)) leads to an increased electron affinity and introduces higher ambipolarity. Organic thin film transistors fabricated from the novel PDPP-BO exhibit charge carrier mobility of 0.6 and 0.3 cm2 Vs⁻1 for electrons and holes, respectively. Due to the high sensitivity of the PDPP-based material and the balanced transport in PDPP-BO, its application as an NIR detector in an OPT architecture is presented. By maintaining a high on/off ratio (9 × 104), ambipolar OPTs are shown with photoresponsivity of 69 and 99 A W⁻1 and specific detectivity of 8 × 107 for the p-type operation and 4 × 109 Jones for the n-type regime. The high symmetric NIR-ambipolar OPTs are also evaluated as ambipolar photo-inverters, and show a 46% gain enhancement under illumination.

Enhanced osteogenesis and physicochemical properties of PMMA bone cement with SrBG/HA porous core-shell microspheres.

Artificial bone graft with osteoconductivity, angiogenesis, and immunomodulation is promising clinical therapeutics for the reluctant healing process of bone defects. Among various osteogenic substitutes, polymethyl methacrylate (PMMA) bone cement is a quit competitive platform due to its easy deployment to the bone defects with irregular shape and biomimetic mechanical properties. However, the biologically inert essence of PMMA is reliant on the passive osseointegration and cannot provide sufficient biologic cues to induce fast bone repair. Bioactive glass could serve as an efficient platform for the active osteogenesis of PMMA via ionic therapy and construction of alkaline microenvironment. However, the direct of deployment of bioactive glass into PMMA may trigger additional cytotoxicity and hinder cell growth on its surface. Hence we incorporated ionic therapy as osteogenic cue into the PMMA to enhance the biomedical properties. Specifically, we synthesized core-shell microspheres with a strontium-doped bioactive glass (SrBG) core and hydroxyapatite (HA) shell, and then composited them with PMMA to introduce multifunctional effects of HA incorporation, alkaline microenvironment construction, and functional ion release by adding microsphere. We preparedxSrBG@HA/PMMA cements (x= 30, 40, 50) with varied microsphere content and evaluated impacts on mechanical/handling properties, ion release, and investigated the impacts of different composite cements on proliferation, osteogenic differentiation, angiogenic potential, and macrophage polarization. These findings provide new perspectives and methodologies for developing advanced bone biomaterials to promote tissue regeneration.

SbYS1 and SbWRKY72 regulate Cd tolerance and accumulation in sweet sorghum.

MAIN CONCLUSION: SbYS1 and its upstream transcription factor SbWRKY72 were involved in Cd tolerance and accumulation and are valuable for developing sweet sorghum germplasm with high-Cd tolerance or accumulation ability through genetic manipulation. Cadmium (Cd) is highly toxic and can severely affect human health. Sweet sorghum, as an energy crop, shows great potential in extracting cadmium from Cd-contaminated soils. However, its molecular mechanisms of Cd-tolerance and -accumulation remain largely unknown. Here, we isolated a YSL family gene SbYS1 from the sweet sorghum genotype with high Cd accumulation ability and the expression of SbYS1 in roots was induced by cadmium. GUS staining experiment exhibited that SbYS1 was expressed in the epidermis and parenchyma tissues of roots. Further subcellular localization analysis suggested that SbYS1 was localized in the endoplasmic reticulum and plasma membrane. Yeast transformed with SbYS1 exhibited a sensitive phenotype compared to the control when exposed to Cd-NA (chelates of cadmium and nicotianamine), indicating that SbYS1 may absorb cadmium in the form of Cd-NA. Arabidopsis overexpressing SbYS1 had a longer root length and accumulated less Cd in roots and shoots. SbWRKY72 bound to the promoter of SbYS1 and negatively regulated the expression of SbYS1. Transgenic Arabidopsis of SbWRKY72 showed higher sensitivity to cadmium and increased cadmium accumulation in roots. Our results provide references for improving the phytoremediation efficiency of sweet sorghum by genetic manipulation in the future.

Enhanced ·OH-Scavenging Activity of Cu-CeOx Nanozyme via Resurrecting Macrophage Nrf2 Transcriptional Activity Facilitates Diabetic Wound Healing.

Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing.

Zonation of bulk and rhizosphere soil bacterial communities and their covariation patterns along the elevation gradient in riparian zones of three Gorges reservoir, China.

Zonation is a typical pattern of soil distribution and species assembly across riparian habitats. Microorganisms are essential members of riparian ecosystems and whether soil microbial communities demonstrate similar zonation patterns and how bulk and rhizosphere soil microorganisms interact along the elevation (submergence stress) gradient remain largely unknown. In this study, bulk and rhizosphere (dominant plant) soil samples were collected and investigated across riparian zones where the submergence stress intensity increased as the elevation decreased. Results showed that the richness of bacterial communities in bulk and rhizosphere soil samples was significantly different and presented a zonation pattern along with the submergence stress gradient. Bulk soil at medium elevation that underwent moderate submergence stress had the most abundant bacterial communities, while the species richness of rhizobacteria at low elevation that experienced serious submergence stress was the highest. Additionally, principal coordinate analysis (PCoA) and significance tests showed that bulk and rhizosphere soil samples were distinguished according to the structure of bacterial communities, and so were bulk or rhizosphere soil samples from different elevations. Redundancy analysis (RDA) and Mantel test suggested that bacterial communities of bulk soil mainly relied on the contents of soil organic matter, total carbon (TC), total nitrogen (TN), sodium (Na), calcium (Ca) and magnesium (Mg). Contrastingly, the contents of Na and Mg were the main factors explaining the variation in rhizobacterial community composition. Correlation and microbial source tracking analyses showed thatthe relationship of bulk and rhizosphere soil bacteria became much stronger, and the rhizosphere soil may get more bacterial communities from bulk soil with the increase in submergence severity. Our results suggest that the abiotic and biotic components of the riparian ecosystem are closely covariant along the submergence stress gradient and imply that the bacterial community may be a key node linking soil physiochemical properties and vegetation communities.

Single-plane osteotomy model is inaccurate for evaluating the optimal strategy in treating vertical femoral neck fractures: A finite element analysis.

BACKGROUND AND OBJECTIVES: The conventional method for simulating vertical femoral neck fractures (vFNFs) is via a vertical single-plane osteotomy (SPO) across the entire femur. However, the accuracy of SPO for evaluating the optimal internal fixation strategy (IFS) and the appropriate assessment parameters is not clear. This study thus aimed to examine the accuracy of SPO in evaluating IFSs and to identify appropriate evaluation parameters using finite element analysis. METHODS: Eighty patient-specific finite element models were developed based on CT images from eight vFNF patients. The natural fracture model was built using structural features of the affected side, while the SPO was simulated on the healthy side. Five different IFSs were applied to both the natural fracture and SPO groups. Thirteen parameters, including stress, displacement, and stiffness, were subjected to a two-way repeated measures ANOVA to determine the effect of IFSs and fracture morphology on stability. A Pearson correlation analysis was performed on varied parameters with various IFSs to identify independent parameters. Based on these independent parameters, the entropy evaluation method (EEM) score was used to rank the performance of IFSs for each patient. RESULTS: Eight of the thirteen parameters were significantly influenced by IFSs (p < 0.05), two by fracture morphology (p < 0.01), and none by the interaction between IFS and fracture morphology. In the natural fracture group, parameters including screw stress and displacement, bone cut rate (BCR), and compression effects varied independently with distinct IFSs. In the SPO group, trunk displacement, BCR, cut-out risk, and compression effects parameters changed independently. The BCR of the Alpha strategy was significantly higher than that of the Inverted strategy in the natural fracture group (p = 0.002), whereas the opposite was observed in the SPO group (p = 0.016). Regarding compression effects, two IFS pairings in the natural fracture group and seven IFS pairings in the SPO group exhibited significant differences. None of the five IFSs achieved the optimal EEM score for each patient. CONCLUSIONS: The single-plane osteotomy model may have limitations in assessing IFSs, particularly when the bone cut rate and compression effects are the main influencing factors. Parameters of the screw stress and displacement, BCR, and compression effects appear to be relevant in evaluating IFSs for natural fracture models. It indicates that individualized natural fracture models could provide more comprehensive insights for determining the optimal IFS in treating vFNFs.

Biomimetic Targeting Nanoadjuvants for Sonodynamic and Chronological Multi-Immunotherapy against Holistic Biofilm-Related Infections.

Biofilm-related infections (BRIs) present significant challenges owing to drug resistance, adverse immune responses, and implant failure; however, current approaches inadequately cater to the diverse therapeutic requirements at different stages of infection. To address this issue, a multi-immunotherapy strategy in combination with sonodynamic therapy is proposed for the chronological treatment of BRIs. Macrophage membrane-decorated targeting sonosensitive nanoadjuvants are fabricated to load cytosine-phosphate-guanine oligodeoxynucleotide (CPG-ODN) or microRNA (miR)-21-5p. In the early stages of BRI (Stage I), CPG-ODN-loaded nanoadjuvants (CPG@HMPN@M) promote the formation of neutrophil extracellular traps to capture and neutralize detached microbes. During the late stage of infection (Stage II), CPG-ODNs redirect macrophage polarization into the M1 phase to combat infections via TLR9/Myd88/TRAF6 pathway. During these stages, CPG@HMPN@M generates singlet oxygen through sonodynamic processes, eradicating the biofilms under US irradiation. Once the BRIs are eliminated, miR-21-5p-loaded nanoadjuvants (miR@HMPN@M) are delivered to the lesions to suppress excessive inflammation and promote tissue integration by evoking macrophage M2 polarization during the repair phase (Stage III) through PTEN/PI3K/Akt pathway. This innovative approach aims to provide comprehensive treatment strategies for the chronological treatment of BRI by effectively eliminating infections, promoting tissue restoration, and implementing different immune regulations at different stages, thus demonstrating promising clinical value.

Association between extremely high-density lipoprotein cholesterol and adverse cardiovascular outcomes: a systematic review and meta-analysis.

Background: The association between high-density lipoprotein cholesterol (HDL-C) and adverse cardiovascular outcomes is understudied. Based on cohort studies, the current study aimed to investigate the association of extremely high HDL-C with all-cause, atherosclerotic cardiovascular disease (CVD) mortality, and stroke risk. Methods: A systematic literature search in Embase, PubMed, Cochrane Library, and Web of Science was performed to collect relevant cohort studies published before August 20, 2022. A random-effects model was used to pool relative risks (RRs) and 95% confidence intervals (CIs). Results: A total of 17 cohort studies involving 19,630,829 participants were included, encompassing 18,547,132 total deaths (1,328,036 CVD deaths). All-cause mortality, CVD mortality, and stroke risk in the extremely high HDL-C group were increased by 15% (RR = 1.15, 95% CI:1.05-1.25), 14% (RR = 1.14, 95% CI:0.96-1.35) and 14% (RR = 1.14, 95% CI:0.82-1.58), compared to the normal HDL-C group. In subgroup analyses, extremely high HDL-C was associated with a reduced risk of CVD mortality in women and a lower risk of stroke in men compared to normal HDL-C levels. Conclusions: The extremely high levels of HDL-C were associated with elevated risks of all-cause mortality, CVD mortality, and stroke. More well-designed studies are needed to confirm our findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=370201, identifier: CRD42022370201.

What makes vertical femoral neck fracture with posterior inferior comminution different? An analysis of biomechanical features and optimal internal fixation strategy.

BACKGROUND AND PURPOSE: Fracture comminution occurs in 83.9%-94% of vertical femoral neck fractures (VFNFs), the majority of which were located in posterior-inferior region, and poses a clinical challenge in fixation stability. We conducted a subject-specific finite element analysis to determine the biomechanical features and optimal fixation selection for treating VFNF with posterior-inferior comminution. PATIENTS AND METHODS: Eighteen models with three fracture types (VFNF without comminution [NCOM], with comminution [COM], with comminution + osteoporosis [COMOP]) and six internal fixation types (alpha [G-ALP], buttress [G-BUT], rhomboid [G-RHO], dynamic hip screw [G-DHS], invert triangle [G-ITR], femoral neck system (G-FNS)) were created based on the computed tomography data. By using the subject-specific finite element analysis method, stiffness, implant stress, yielding rate (YR) were compared. Additionally, in order to elucidate distinct biomechanical characters of different fracture types and fixation strategies, we calculated interfragmentary movement (IFM), detached interfragmentary movement (DIM), shear interfragmentary movement (SIM) of all fracture surface nodes. RESULTS: Generally, in comparison with NCOM, COM showed a 30.6% reduction of stiffness and 1.46-times higher mean interfragmentary movement. Besides, COM had a 4.66-times (p = 0.002) higher DIM at the superior-middle position, but similar SIM across fracture line, which presented as varus deformation. In COM and COMOP, among all six fixation strategies, G-ALP had significantly the lowest IFM (p<0.001) and SIM (p<0.001). Although G-FNS had significantly highest IFM and SIM (p<0.001), it had the highest stiffness and lowest DIM (p<0.001). In COMOP, YR was the lowest in G-FNS (2.67%). CONCLUSIONS: Posterior-inferior comminution primarily increases superior-middle detached interfragmentary movement in VFNF, which results in varus deformation. For comminuted VFNF with or without osteoporosis, alpha fixation has the best interfragmentary stability and anti-shear property among six current mainstream fixation strategies, but a relatively weaker stiffness and anti-varus property compared to fixed-angle devices. FNS is advantageous owing to stiffness, anti-varus property and bone yielding rate in osteoporosis cases, but is insufficient in anti-shear property.

Shift from flooding to drying enhances the respiration of soil aggregates by changing microbial community composition and keystone taxa.

Changes in the water regime are among the crucial factors controlling soil carbon dynamics. However, at the aggregate scale, the microbial mechanisms that regulate soil respiration under flooding and drying conditions are obscure. In this research, we investigated how the shift from flooding to drying changes the microbial respiration of soil aggregates by affecting microbial community composition and their co-occurrence patterns. Soils collected from a riparian zone of the Three Gorges Reservoir, China, were subjected to a wet-and-dry incubation experiment. Our data illustrated that the shift from flooding to drying substantially enhanced soil respiration for all sizes of aggregate fractions. Moreover, soil respiration declined with aggregate size in both flooding and drying treatments. The keystone taxa in bacterial networks were found to be Acidobacteriales, Gemmatimonadales, Anaerolineales, and Cytophagales during the flooding treatment, and Rhizobiales, Gemmatimonadales, Sphingomonadales, and Solirubrobacterales during the drying treatment. For fungal networks, Hypocreales and Agaricalesin were the keystone taxa in the flooding and drying treatments, respectively. Furthermore, the shift from flooding to drying enhanced the microbial respiration of soil aggregates by changing keystone taxa. Notably, fungal community composition and network properties dominated the changes in the microbial respiration of soil aggregates during the shift from flooding to drying. Thus, our study highlighted that the shift from flooding to drying changes keystone taxa, hence increasing aggregate-scale soil respiration.

In-hospital waiting time to surgery and functional outcomes in geriatric hip fractures: a directed acyclic graph-based preplanned analysis from a prospective multicenter cohort study.

BACKGROUND: The early recovery of hip function after hip fracture surgery values more attention, especially for patients with delayed surgery of longer than 48 h. We aim to evaluate the associations of in-hospital surgical waiting time with the functional outcomes [Harris Hip Score (HHS), Parker Mobility Score (PMS), and EuroQol 5 dimensions VAS (visual analogue scale) score (EQ-5D VAS)] in elderly patients who sustained hip fractures. MATERIALS AND METHODS: Data on sociodemographic and clinical factors were prospectively collected using a multicenter hip fracture registry system. Participants in the cohort underwent a 12-month follow-up investigation. After adjusting potential confounders identified by the directed acyclic graphs, the associations between surgical waiting time longer than 48 h and functional outcomes were estimated by log-binomial regression and multivariable linear regression models with generalized estimating equations. RESULTS: Of 863 survival participants with available functional data at 12 months after surgery, an increased risk was obtained from receiving surgery after 48 h and the poor functional outcomes (HHS<80: relative risk (RR)=1.56, 95% CI: 1.00-2.51; PMS<7: RR=1.49, 95% CI: 1.13-2.01; EQ-5D VAS<80: RR=1.97, 95% CI: 1.57-2.47). In-hospital waiting time greater than 48 h were time-invariantly associated with lower PMS during recovery (-0.44 units 95% CI: -0.70 to -0.18). In addition, delayed surgery was time-varying associated with HHS and EQ-5D VAS. CONCLUSIONS: The associations between in-hospital waiting time and postoperative functional score suggest that delayed surgery can lead to poor functional outcomes, especially in patients waiting longer than 72 h from injury. Delayed surgery mainly impacted hip function and mobility recovery with a slower speed in early recovery of the first 3 months. More attention should be paid to mechanisms behind the associations between delayed surgery on general healthy status.

Regulated contribution of local and systemic immunity to new bone regeneration by modulating B/Sr concentration of bioactive borosilicate glass.

The local immune response induced by bioactive borosilicate glass (BG) plays a vital role in bone regeneration, but its effect in the systemic immune response of distal tissues, such as spleen, remains unknown. In this study, the network structures and the relative theoretical structural descriptors (Fnet) of the novel BG composition containing boron (B) and strontium (Sr) were calculated and stimulated by molecular dynamics (MD) simulation, and the linear relationships of Fnet and B and Sr releasing rate in pure water and simulate body fluid were built. Next, the synergistic effects of the released B and Sr on promoting osteogenic differentiation, angiogenesis, and macrophage polarization were analyzed in vitro and convinced in rats skull models in vivo. Results show that the optimal synergistic effects of B and Sr both in vitro and in vivo released from 1393B2Sr8 BG increased vessel regeneration, modulated M2 macrophages polarization and promoted new-bone formation. Interestingly, the 1393B2Sr8 BG was found to mobilize monocytes from the spleen to the defects and subsequently modulate them into M2 macrophages. Then, these modulated cells cycled from the bone defects back to the spleen. To analyze the necessity of spleen-derived immune cells in bone regeneration, two contrasting rat models (with/without spleen) of skull defects were furtherly established. As results, rats without spleen had fewer M2 macrophages surrounding skull defects and the bone tissues recovered more slowly, indicating the beneficial effects on bone regeneration of circulating monocytes and polarized macrophages provided by spleen. The present study provides a new approach and strategy in optimizing complex composition of novel BG and sheds light on the importance of spleen through modulating systemic immune response to contribute to local bone regeneration.

Enzymatic bionanocatalysts for combating peri-implant biofilm infections by specific heat-amplified chemodynamic therapy and innate immunomodulation.

Bacterial biofilm-associated infection is a life-threatening emergency contributing from drug resistance and immune escape. Herein, a novel non-antibiotic strategy based on the synergy of bionanocatalysts-driven heat-amplified chemodynamic therapy (CDT) and innate immunomodulation is proposed for specific biofilm elimination by the smart design of a biofilm microenvironment (BME)-responsive double-layered metal-organic framework (MOF) bionanocatalysts (MACG) composed of MIL-100 and CuBTC. Once reaching the acidic BME, the acidity-triggered degradation of CuBTC allows the sequential release of glucose oxidase (GOx) and an activable photothermal agent, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). GOx converts glucose into H2O2 and gluconic acid, which can further acidify the BME to accelerate the CuBTC degradation and GOx/ABTS release. The in vitro and in vivo results show that horseradish peroxidase (HRP)-mimicking MIL-100 in the presence of self-supplied H2O2 can catalyze the oxidation of ABTS into oxABTS to yield a photothermal effect that breaks the biofilm structure via eDNA damage. Simultaneously, the Cu ion released from the degraded CuBTC can deplete glutathione and catalyze the splitting of H2O2 into •OH, which can effectively penetrate the heat-induced loose biofilms and kill sessile bacteria (up to 98.64%), such as E. coli and MRSA. Particularly, MACG-stimulated M1-macrophage polarization suppresses the biofilm regeneration by secreting pro-inflammatory cytokines (e.g., IL-6, TNF-α, etc.) and forming a continuous pro-inflammatory microenvironment in peri-implant biofilm infection animals for at least 14 days. Such BME-responsive strategy has the promise to precisely eliminate refractory peri-implant biofilm infections with extremely few adverse effects.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Nacre-inspired magnetically oriented micro-cellulose fibres/nano-hydroxyapatite/chitosan layered scaffold enhances pro-osteogenesis and angiogenesis.

In situ regeneration of large-segment bone defects is a difficult clinical problem. Here, we innovatively developed magnetically oriented micro-cellulose fibres using nano-hydroxyapatite/chitosan (CEF/Fe3O4/HA/CS) and loaded an NFκB pathway inhibitor on the surface of magnetically oriented cellulose fibres (CEF/Fe3O4/HA/CS/PQQ) prepared as a layered bioscaffold. CEF/Fe3O4/HA/CS/PQQ was constructed by layering HA/CS sheets. Nano-hydroxyapatite was deposited on the surface of cellulose fibres, then the magnetic nanoparticles on the cellulose fibres were aligned on the surface of chitosan under a magnetic field. Oriented cellulose fibres enhanced the compressive properties of the scaffold, with an average maximum compressive strength of 1.63 â€‹MPa. The CEF/Fe3O4/HA/CS/PQQ layered scaffold was filled into the body, and the acute inflammatory response (IL-1ß and TNF-α) was suppressed through the early sustained release of PQQ. The CEF/Fe3O4/HA/CS/PQQ-layered scaffold further inhibited the osteoclasts differentiation. It was further found that the nano-hydroxyapatite on the surface of oriented cellulose fibres promoted the formation and migration of new blood vessels, accelerated the processing of collagen-I fibres to cartilage, and endochondral ossification. Hence, the development of the CEF/Fe3O4/HA/CS/PQQ layered scaffold with oriented fibres guides bone growth direction and pro-osteogenesis activity and provides a novel strategy for the in situ regeneration of large segmental bone defects.

SrFe12O19-doped nano-layered double hydroxide/chitosan layered scaffolds with a nacre-mimetic architecture guide in situ bone ingrowth and regulate bone homeostasis.

Osteoporotic bone defects result from an imbalance in bone homeostasis, excessive osteoclast activity, and the weakening of osteogenic mineralization, resulting in impaired bone regeneration. Herein, inspired by the hierarchical structures of mollusk nacre, nacre exhibits outstanding high-strength mechanical properties, which are in part due to its delicate layered structure. SrFe12O19 nanoparticles and nano-layered double hydroxide (LDH) were incorporated into a bioactive chitosan (CS) matrix to form multifunctional layered nano-SrFe12O19-LDH/CS scaffolds. The compressive stress value of the internal ordered layer structure matches the trabecular bone (0.18 â€‹MPa). The as-released Mg2+ ions from the nano-LDH can inhibit bone resorption in osteoclasts by inhibiting the NFκB signaling pathway. At the same time, the as-released Sr2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP-2/SMAD signaling pathway. In vivo, the Mg2+ ions released from the SrFe12O19-LDH/CS scaffolds inhibited the release of pro-inflammatory factors (IL-1ß and TNF-α), while the as-released Sr2+ ions promoted osteoblastic proliferation and the mineralization of osteoblasts inside the layered SrFe12O19-LDH/CS scaffolds. Immunofluorescence for OPG, RANKL, and CD31, showed that stable vasculature could be formed inside the layered SrFe12O19-LDH/CS scaffolds. Hence, this study on multifunctional SrFe12O19-LDH/CS scaffolds clarifies the regulatory mechanism of osteoporotic bone regeneration and is expected to provide a theoretical basis for the research, development, and clinical application of this scaffold on osteoporotic bone defects.

The Impact of COVID-19 on SARSCoV-2-Negative Elderly Patients with Hip Fractures: A Single-Center Retrospective Study from Shanghai, China.

Purpose: Coronavirus disease 2019 (COVID-19) has brought an unprecedented change in wellbeing globally. The spread of the pandemic reportedly reduced the incidence of activity-related trauma, while that of fragility fractures remained stable. Here, we aimed to identify the risk factors associated with the prognosis of SARS-CoV-2 negative elderly patients with hip fractures. Patients and Methods: This retrospective study included elderly patients with hip fractures between 1st January and 9th May during the COVID-19 pandemic (Experiment group) and the same period from 2017 to 2019 (Control group). Perioperative mortality, complications, and functional recovery were compared between two groups of different time frame in the total cohort and patients who received surgical treatment. Multiple linear regression was carried out to identify the risk factors influencing the prognosis of COVID-negative elderly patients with hip fractures. Results: The proportion of patients with admission time less than 24 hours and the 6-month postoperative Parker score were significantly decreased during COVID-19 compared with the pre-COVID-19 period (p < 0.001). Multiple linear regression demonstrated that TTA (defined as time from injury to admission), rehabilitation after discharge and outpatient follow-up were associated with the 6-month Parker score in the total population (p < 0.001) and in patients who received surgical treatment (p < 0.001). Conclusion: Elderly patients with hip fractures had a poorer prognosis in epidemic period despite being COVID-19 negative. Factors including timely admission, postoperative follow-up, and rehabilitation could optimize safety and significantly improve the prognosis of elderly COVID-19 negative patients with hip fractures, even during a pandemic.

The beneficial potential of magnesium-based scaffolds to promote chondrogenesis through controlled Mg2+ release in eliminating the destructive effect of activated macrophages on chondrocytes.

Chondral defects caused by osteoarthritis (OA) are common but difficult to manage due to their limited capacity for self-repair. Further, the activated macrophages induced by OA stimulates chondrocytes degradation and inhibits regeneration, further impeding cartilage repair. Therefore, biomaterials with the potential for blocking vicious cycles between activated macrophages and chondrocytes would be promising for use in the treatment of chondral defects caused by OA. In this study, we fabricated porous Mg-Nd-Zn-Zr alloy (denoted JDBM) scaffolds coated with polydopamine (PDA) and investigated their cytocompatibility and impact on immunoregulation. Mesenchymal stem cells (MSCs) were co-cultured in supernatant from M1-polarized macrophages pretreated with extracts from JDBM scaffolds and the anti-inflammatory effect on the NF-κB pathway and reactive oxygen species (ROS) evaluated. JDBM scaffolds could reduce M1 macrophage numbers, while promoting those of M2 macrophages; recruit MSCs; and enhance chondrogenesis. Furthermore, lipopolysaccharide (LPS)-induced p65 translocation to the nucleus was inhibited by JDBM scaffolds, with ROS production and matrix metalloproteinase (MMP) expression also suppressed. These findings suggest that JDBM scaffolds can both promote chondrogenesis and effectively attenuate local inflammatory responses by transforming macrophages from the M1 to M2 subtype and down-regulating NF-κB signaling. Hence, JDBM scaffolds could promote chondrogenesis under inflammatory microenvironment and represent a promising material for treatment of chondral defects caused by OA.

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery.

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility. Controlled release is achieved via passive diffusion through the porous release control element, which is tuned to specific drug characteristics to accomplish a therapeutic level of ranibizumab in the vitreous. To characterize drug release from the implant, release rate was measured in vitro with starting concentrations of ranibizumab 10, 40, and 100 mg/mL, with release of ranibizumab 40 and 100 mg/mL found to remain quantifiable after 6 months. Using a starting concentration of 100 mg/mL, active release rate at approximately 6 months was consistent after the initial fill and first, second, and third refills, demonstrating reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single 100-µL stroke using the refill needle was shown to replace over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.