Differential attitudes and outcomes of endodontics education between mainland and non-mainland chinese students during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has changed the learning style and campus life of dental students. This study aimed to evaluate the learning attitudes and outcomes of endodontics among mainland Chinese students and non-mainland Chinese students (students from Hong Kong, Macao, and Taiwan) during the pandemic. METHODS: A cross-sectional survey was conducted in November 2022 at the School of Stomatology, Jinan University, utilizing a self-report online questionnaire, including demographic characteristics and attitudes toward the endodontic course and the COVID-19 pandemic. The endodontics scores were collected from recruited students for further analysis. The collected data were analyzed using SPSS 22.0 software, with independent two-sample t-tests to compare continuous variables and chi-square tests for categorical variables. RESULTS: A total of 215 dental students completed the survey, with 126 (58.6%) of them being non-mainland Chinese students. Compared to mainland Chinese students, non-mainland Chinese students had lower scores in both theoretical (63.6 ± 13.5 vs. 83.2 ± 8.00) and skill (88.4 ± 5.38 vs. 90.0 ± 4.91) endodontic assessments. Non-mainland Chinese students reported significantly greater impacts of the COVID-19 pandemic on their learning emotions, personal hygiene, and future career choices compared to mainland Chinese students. CONCLUSIONS: Non-mainland Chinese students had poorer academic performance in endodontics and experienced a greater impact from the COVID-19 pandemic in terms of their studies and lives. Dental educators should consider the diversity of students and take necessary measures to support their mental health and enhance learning outcomes in the post-COVID-19 era.

Serum Retinoic Acid Level and The Risk of Poststroke Cognitive Impairment in Ischemic Stroke Patients.

BACKGROUND: Retinoic acid (RA), an active metabolite of vitamin A, possesses enormous protective effects on vascular systems. It may also be positively related to good functional outcome after ischemic stroke. However, whether circulating RA concentration is associated with poststroke cognitive impairment (PSCI) remains unclear. This study aimed to detect the association between RA level and PSCI among patients with first-ever acute ischemic stroke. METHODS: Two hundred and 61 consecutive patients were prospectively recruited during March 2018 and March 2019. Serum RA concentration was measured at admission for all patients. We also performed cognitive function examination using the Montreal Cognitive Assessment (MoCA) at admission and at every follow-up visit. Patients with MoCA score less than 26 were identified as developing PSCI. RESULTS: The median serum RA level was 2.0 ng/mL (interquartile range, 1.1-3.2 ng/mL) after admission. Patients diagnosed as PSCI at admission, 1-month and 3-month were 53 (20.3%), 91 (34.6%), and 141 (54.0%), respectively. Univariate analysis showed that reduced RA level was correlated with PSCI at 3-month (P = .003), but not at admission (P = .416) and 1-month poststroke (P = .117). After adjusting for all potential confounders, the odds ratio for the lowest tertile of RA, compared with the highest tertile, was 1.97 (95% confidence interval, 1.01-3.83, P = .046) for PSCI at 3 months. Furthermore, multiple-adjusted spline regression model further confirmed the dose-response relationships between RA level and 3-month PSCI (P < .001). CONCLUSIONS: Decreasing serum RA level might be associated with 3-month PSCI in ischemic stroke patients.

Preparation and cytocompatibility of a novel bismuth aluminate/calcium phosphate cement with high radiopacity.

In a minimally invasive surgery, using a bone cement being radiologically detectable is vital to the success of the procedure and avoiding cement leakage in the early stage. The radiopacity of calcium phosphate cement (CPC) is inadequate, thus limiting its clinic application in this area. In this work, bismuth aluminate (BiA) was employed as a radiopaque agent for CPC. The influences of BiA on physicochemical, radiopaque and in vitro biocompatible properties of CPC were investigated. With the increasing content of BiA, the setting time and the compressive strength of CPC were augmented, while the injectability of the cement pastes was reduced. The radiopacity of CPC was significantly improved by adding more than 6 wt.% BiA. CPC specimens with less than 12 wt.% BiA showed good cellular affinity. Moreover, the CPC containing 6 and 9 wt.% BiA promoted the cell growth and ALP activity of mouse bone marrow mesenchymal stem cells when compared with the control. On the basis of its improved radiopacity and cytocompatibility, the radiopaque CPC with 6 ~ 9 wt.% BiA is expected to be a potential substitute for bone defect restoration via minimally invasive surgery. CPC with bismuth aluminate reveals better radiopacity and cell affinity along with proper physicochemical properties.

Neuropsychiatric Features of Neurosyphilis: Frequency, Relationship with the Severity of Cognitive Impairment and Comparison with Alzheimer Disease.

BACKGROUND: The pattern of neuropsychiatric features of patients with neurosyphilis and the impact of the severity of cognitive impairment on neuropsychiatric syndromes are unknown. OBJECTIVE: We aim to assess the neuropsychiatric features of patients with neurosyphilis, and compare the impact of the severity of cognitive impairment on the neuropsychiatric syndromes between neurosyphilis and Alzheimer disease (AD). METHODS: Neuropsychiatric symptoms and the degree of cognitive impairment were assessed in a case-control study of 91 neurosyphilis, 162 AD, 157 mild cognitive impairment, and 139 normal controls by the Neuropsychiatric Inventory (NPI) scale and Clinical Dementia Rating scale, respectively. Factor analysis was performed on the 12 NPI items. RESULTS: Factor analysis showed that patients with neurosyphilis showed more severe neuropsychiatric syndromes at the dementia stage than those neurosyphilis patients at the mild cognitive impairment stage, while neuropsychiatric manifestations were equally common among the different stages of dementia (all p < 0.05). Frontal lobe syndrome was more severe in patients with neurosyphilis than in patients with AD from the early mild cognitive impairment stage to the moderate dementia stage (all p < 0.01). CONCLUSIONS: Patients with neurosyphilis show different patterns of neuropsychiatric syndromes at the mild cognitive impairment and dementia stages, and differ from patients with AD.

Hippocampal region metabolites and cognitive impairment in patients with general paresis: based on 1H-proton magnetic resonance spectroscopy.

Background: This study utilizes Hydrogen proton magnetic resonance spectroscopy (1H-MRS) to investigate metabolite concentrations in the bilateral hippocampus of general paresis (GP) patients. Methods: A total of 80 GP patients and 57 normal controls (NCs) were enrolled. Metabolite ratios in the bilateral hippocampus were measured using 1H-MRS. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Based on MMSE scores, participants were categorized into normal control, mild cognitive impairment, and moderate-severe dementia groups. Metabolite ratios (N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/creatine (Cr), N-acetylaspartate (NAA)/choline (Cho), myoinositol (MI)/creatine (Cr), choline (Cho)/N-acetylaspartate (NAA)) were compared between groups, and correlations between metabolite ratios and cognitive performance were examined. Results: MMSE scores progressively decreased in the normal, mild cognitive impairment, and moderate-severe dementia groups (p < 0.001). The moderate-severe dementia group showed significantly lower NAA/Cr ratios in the left hippocampus region (L-NAA/Cr ratios) (p < 0.001) and higher Cho/NAA ratios in the left hippocampus region (L-Cho/NAA ratios) (p < 0.05) compared to the other groups. However, differences in L-NAA/Cr and L-Cho/NAA ratios between the mild cognitive impairment group and the NC group were not significant in the hippocampus region (p > 0.05). NAA/Cho and NAA/Cr ratios in the right hippocampus region (R-NAA/Cho and R-NAA/Cr ratios) in the moderate-severe dementia group were lower than those in the control group (p < 0.05). No correlation was found between metabolite ratios and MMSE scores in bilateral hippocampus regions. Conclusion: There are distinctive metabolic characteristics in the hippocampus of GP patients. GP patients exhibited lower NAA/Cr and NAA/Cho ratios in the bilateral hippocampus, indicating neuron loss in these areas, which may become more pronounced as the disease progresses.

Seasonal characteristics of nosocomial infection in a psychiatric hospital in China with different nosocomial prevention and control backgrounds: a retrospective study.

This study aimed to investigate the relationship between various prevention and control measures for nosocomial infections (NIs) in psychiatric hospitals and patients with mental disorders. This study aimed to determine the characteristics of NIs in psychiatric hospitals and provide a reference for infection prevention and control in this setting. Data from the NI monitoring system of a psychiatric hospital in southeastern China were analysed. Patients who were hospitalized for mental disorders from January 1, 2016, to November 30, 2019, were classified into the non-COVID-19 containment group (NC19C group, n = 898), while those who were hospitalized from January 25, 2020, to November 30, 2022, were classified into the COVID-19 containment group (C19C group, n = 840). The data were analysed using SPSS version 22.0, and independent sample t tests, chi-square tests, correlation analyses, and multivariate logistic regression analyses were performed. A significance level of P < 0.0024 was applied. The incidence rate of NIs was higher in autumn in the NC19C group, while no seasonal difference was detected in the C19C group (P < 0.0024). Further analysis revealed that in the C19C group, the risk of hospitalized patients with mental disorders developing hospital-acquired pneumonia in spring was 0.362 times that in winter (OR = 0.362, 95% CI = 0.200 ~ 0.656, P = 0.001), and in summer, the risk was 0.342 times that in winter (OR = 0.342, 95% CI = 0.185 ~ 0.633 P = 0.001). Patients aged 18-44 years had a 4.260 times higher risk of developing hospital-acquired upper respiratory tract infections than did those aged 60 years and older (OR = 4.260, 95% CI = 2.143 ~ 8.470; P = 0.000). The risk of acquiring urinary tract infections in the hospital was 0.324 times greater among patients aged 18-44 years than for patients aged 60 years and older (OR = 0.324, 95% CI = 0.171-0.613; P = 0.001). The NC19C group did not exhibit the aforementioned differences. During the NC19C period, differences were observed in the diagnosis of hospital-acquired infections and sex (all P = 0.000). Psychiatric hospitals exhibit distinct nosocomial infection characteristics under the context of various infection control measures. Against the backdrop of strengthened infection control, the nosocomial infection characteristics of psychiatric hospitals may be associated with the features of mental disorders.

CSF levels of the neuronal injury biomarker visinin-like protein-1 in Alzheimer's disease and dementia with Lewy bodies.

The overlapping clinical features of Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB) make differentiation difficult in the clinical environment. Evaluating the CSF levels of biomarkers in AD and DLB patients could facilitate clinical diagnosis. CSF Visinin-like protein-1 (VILIP-1), a calcium-mediated neuronal injury biomarker, has been described as a novel biomarker for AD. The aim of this study was to investigate the diagnostic utility of CSF VILIP-1 and VILIP-1/Aß1-42 ratio to distinguish AD from DLB. Levels of CSF VILIP-1, t-tau, p-tau181P , Aß1-42 , and α-synuclein were measured in 61 AD patients, 32 DLB patients, and 40 normal controls using commercial ELISA kits. The results showed that the CSF VILIP-1 level had significantly increased in AD patients compared with both normal controls and DLB patients. The CSF VILIP-1 and VILIP-1/Aß1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. Additionally, CSF VILIP-1 levels were positively correlated with t-tau and p-tau181P within each group and with α-synuclein in the AD and control groups. We conclude that CSF VILIP-1 could be a diagnostic marker for AD, differentiating it from DLB. The analysis of biomarkers, representing different neuropathologies, is an important approach reflecting the heterogeneous features of AD and DLB. Neuronal Ca(2+) -sensor protein VILIP-1 has been implicated in the calcium-mediated neuronal injury and pathological change of AD. The CSF VILIP-1 and VILIP-1/Aß1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. CSF VILIP-1 is a useful biomarker for AD. Evaluating the CSF levels of VILIP-1 in AD and DLB patients could facilitate clinical diagnosis.

Synthesis, Characterization, In Vitro Cytological Responses, and In Vivo Bone Regeneration Effects of Low-Crystalline Nanocarbonated Hydroxyapatite.

Hydroxyapatite (HA) has been commonly used as an alternative bone substitute. But it has drawbacks, such as poor degradation and limited osteogenesis. Low-crystalline carbonated hydroxyapatite (L-CHA), which has greater biodegradability than HA, is suggested as one of the main components of bone minerals, but the exact mechanism behind the roles of carbonate substituted in biological behaviors of low-crystalline HA is still a mystery. In this study, L-CHAs with different carbonate contents were prepared, and the effects of the content on the physicochemical properties, in vitro cytological responses, and in vivo bone defects repair effects of L-CHAs were investigated. The results demonstrated that CO32- had successfully entered the lattice structure of L-CHAs with a maximum content of 9.2 wt %. Both low-crystalline undoped HA (L-HA) and L-CHAs were nanocrystalline (20-30 nm) with significantly higher specific surface areas, protein adsorption capacities, and biodegradability compared to high-crystalline HA (H-HA) with submicron crystalline size (200-400 nm). Besides, the amounts of the adsorbed protein and released Ca2+ ions increased in a carbonate-content-dependent manner. Compared to L-HA and H-HA, L-CHAs promoted the adhesion and proliferation of bone marrow mesenchymal stem cells and significantly upregulated the levels of alkaline phosphatase (ALP) activity and the expression of osteogenesis-related genes. In addition, L-CHA-9 not only showed a faster biodegradation rate but also effectively promoted bone regeneration when implanted in the critical-sized bone defects of rabbit femora. This study provided evidence for the development of L-CHA as a promising biodegradable and bioactive material with great osteoconductivity and osteogenic capability with respect to conventional HA.

Physicochemical properties and cytocompatibility of radiation-resistant and anti-washout calcium phosphate cement by introducing artemisia sphaerocephala krasch gum.

The anti-washout ability of calcium phosphate cement (CPC) determines the effectiveness of CPC in clinical application. The γ-ray irradiation method often used in the sterilization process of CPC products is easy to degrade some commonly polymer anti-washout agent, which greatly reduces its anti-washout performance. Artemisia sphaerocephala Krasch gum (ASKG) has the potential of radiation resistance and anti-washout, but no one has considered its performance as anti-washout agent of CPC and mechanism of radiation resistance and anti-washout so far. In this study, we report the effect of γ-ray on ASKG and the effectiveness of ASKG for enhancing of radiation resistance and anti-washout ability of CPC, the physical, chemical properties and in vitro cell behaviors of ASKG-CPCs were also investigated. The results showed that addition of ASKG before and after irradiation could significantly enhanced the anti-washout performance of CPC, which is differ from conventional anti-washout agents. Meanwhile, ASKG-CPCs had an excellent injectable property and biocompatibility, and low content of irradiated ASKG could promote bone differentiation well. We anticipate that the radiation-resistant and anti-washout ASKG-CPCs have potential application prospect in orthopaedic surgery.

Fabrication of 3D printed Ca3Mg3(PO4)4-based bioceramic scaffolds with tailorable high mechanical strength and osteostimulation effect.

Calcium, magnesium and phosphate are predominant constituents in the human bone. In this study, magnesium-calcium phosphate composite bioceramic scaffolds were fabricated utilizing Mg3(PO4)2 and ß-Ca3(PO4)2 as starting materials, and their pore structure was constructed by 3D printing. The porosity and compressive strength of the composite bioceramic scaffolds could be adjusted by altering the sintering temperature and the formula of starting materials. The composite bioceramic scaffolds prepared from 60 wt% Mg3(PO4)2 and 40 wt% ß-Ca3(PO4)2 were dominated by the Ca3Mg3(PO4)4 phase, and this Ca3Mg3(PO4)4-based bioceramic scaffolds possessed the highest compressive strength (12.7 - 92.4 MPa). Moreover, the Ca3Mg3(PO4)4-based bioceramic scaffolds stimulated cellular growth and osteoblastic differentiation of bone marrow stromal cells. The Ca3Mg3(PO4)4-based bioceramic scaffolds as bone regenerative biomaterials are flexible to the requirement of bone defects at various sites.

Fabrication of strontium carbonate-based composite bioceramics as potential bone regenerative biomaterials.

Strontium carbonate (SrC) bioceramics are proposed as potential biomaterials to efficaciously repair the bone defects. However, the development of SrC bioceramics is restricted by their intrinsic low mechanical strength. In this study, SrC-based composite bioceramics (SrC-SrP) were fabricated by incorporating strontium-containing phosphate glass (SrP). The results indicated that aside from the main crystalline phase SrC, new compounds were generated in the SrC-SrP bioceramics. Incorporating 10 wt% SrP promoted densification, thus dramatically improving compressive strength of SrC-SrP bioceramics. The SrC-SrP bioceramics facilitated apatite precipitation on their surface, and sustainedly released strontium, phosphorus and sodium ions. Compared with the well-known ß-tricalcium phosphate bioceramics, the SrC-SrP bioceramics with certain amounts of SrP enhanced proliferation, alkaline phosphatase activity and osteogenesis-related gene expressions of mouse bone mesenchymal stem cells. The SrC-SrP bioceramics with appropriate constituent can serve as novel bone regenerative biomaterials.

A thermostability perspective on enhancing physicochemical and cytological characteristics of octacalcium phosphate by doping iron and strontium.

Investigation of thermostability will lead the groundbreaking of unraveling the mechanism of influence of ion-doping on the properties of calcium phosphates. In this work, octacalcium phosphate (OCP), a metastable precursor of biological apatite, was used as a stability model for doping ions (Fe3+ and Sr2+) with different ionic charges and radii. After treated under hot air at different temperatures (110-200 °C), the phase, morphology, structure, physicochemical properties, protein affinity, ions release, and cytological responses of the ion-doped OCPs were investigated comparatively. The results showed that the collapse of OCP crystals gradually occurred, accompanying with the dehydration of hydrated layers and the disintegration of plate-like crystals as the temperature increased. The collapsed crystals still retained the typical properties of OCP and the potential of conversion into hydroxyapatite. Compared to the undoped OCP, Fe-OCP, and Sr-OCP had lower and higher thermostability respectively, leading to different material surface properties and ions release. The adjusted thermostability of Fe-OCP and Sr-OCP significantly enhanced the adsorption of proteins (BSA and LSZ) and the cytological behavior (adhesion, spreading, proliferation, and osteogenic differentiation) of bone marrow mesenchymal stem cells to a varying extent under the synergistic effects of corresponding surface characteristics and early active ions release. This work paves the way for understanding the modification mechanism of calcium phosphates utilizing ion doping strategy and developing bioactive OCP-based materials for tissue repair.

Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression.

Objectives: To first explore the role of plasma vascular endothelial growth factor (VEGF) concentrations in ketamine's antianhedonic effects, focusing on Chinese patients with treatment-refractory depression (TRD). Methods: Seventy-eight patients with treatment-refractory major depressive disorder (MDD) or bipolar disorder (BD) were treated with six ketamine infusions (0.5 mg/kg). Levels of anhedonia were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) anhedonia item at baseline, day 13 and 26. Plasma VEGF concentrations were examined at the same time points as the MADRS. Results: Despite a significant reduction in anhedonia symptoms in individuals with treatment-refractory MDD (n = 59) or BD (n = 19) after they received repeated-dose ketamine infusions (p < 0.05), no significant changes in plasma VEGF concentrations were found at day 13 when compared to baseline (p > 0.05). The alteration of plasma VEGF concentrations did not differ between antianhedonic responders and non-responders at days 13 and 26 (all ps > 0.05). Additionally, no significant correlations were observed between the antianhedonic response to ketamine and plasma VEGF concentrations (all ps > 0.05). Conclusion: This preliminary study suggests that the antianhedonic effects of ketamine are not mediated by VEGF.

Improving osteogenesis of calcium phosphate bone cement by incorporating with manganese doped ß-tricalcium phosphate.

Lack of osteogenic capacity limits the bone repair effect of calcium phosphate cement (CPC). In present work, bivalent manganese ion (Mn2+) doped ß-tricalcium phosphate (Mn-TCP) was incorporated into CPC to enhance its osteogenic ability. The incorporation of Mn-TCP promoted the hydration reaction of CPC. The presence of Mn2+ made the hydration products finer. When adding 10 wt% Mn-TCP in CPC (Mn-CPC-1), the setting time of CPC was shortened, whereas the strength and injectability were not changed. Mouse Bone marrow mesenchymal stem cells (mBMSCs) on Mn-CPC-1 and CPC with 20 wt% Mn-TCP (Mn-CPC-2) presented better adhesion and spreading behaviors. Besides, Mn-CPC-1 promoted the gene levels of ALP, Col-I and OC while Mn-CPC-2 promoted the gene levels of Runx2 and OC. Cellular behaviors were related to two points: one was the increase of adsorption capacity of proteins (e.g. BSA) after changing the surface properties of bone cements; and the other was the biological role of Mn2+ released from CPC in osteogenesis. All the results indicated that CPC incorporated with 10 wt% Mn-TCP has good osteogenesis and proper physicochemical properties, which will be a prospective biomaterial applying in the area of bone regeneration.

Increasing trimethylamine N-oxide levels as a predictor of early neurological deterioration in patients with acute ischemic stroke.

Background and aims: Trimethylamine N-oxide (TMAO), a pro-atherosclerotic intestinal microbiota metabolite, has mechanistic links to atherosclerosis development and cardiovascular diseases. In this study, we aimed to investigate whether serum TMAO levels could predict early neurological deterioration (END) after acute ischemic stroke.Methods: We prospectively recruited patients with first-ever ischemic stroke and hospitalized within 24 h of symptoms onset during Mar 2018 to Mar 2019. Plasma TMAO levels were quantified using stable isotope dilution high-performance liquid chromatography with tandem mass spectrometry after admission. END was defined as an increase in the total National Institutes of Health Stroke Scale by 2 or more points within 3 days.Results: Of the 362 patients included, END was diagnosed in 97 subjects (26.8%). The median TMAO concentrations were 4.8 µmol/L, with tertile levels as follows: first tertile (<3.9 µmol/L), second tertile (3.9-5.6 µmol/L), and third tertile (>5.6 µmol/L). Patients with END showed higher levels of TMAO (median 5.0 vs. 4.5 µmol/L, P = 0.005) at admission. In univariate logistic analysis, elevated plasma levels of TMAO [odd ratios for highest tertile vs. lowest tertile, 2.14; 95% confidence interval, 1.19-3.82] was a significant predictor of END in patients with ischemic stroke. This association remained significant after controlling for confounders in multivariate logistic analysis. Multiple-adjusted spline regression model further confirmed the dose-response relationship between TMAO levels and END (P < 0.001 for linearity).Conclusions: Our study indicated that increasing TMAO levels at admission might be associated with END after acute ischemic stroke.

BACE1 and Other Alzheimer's-Related Biomarkers in Cerebrospinal Fluid and Plasma Distinguish Alzheimer's Disease Patients from Cognitively-Impaired Neurosyphilis Patients.

BACKGROUND: Patients with spirochetal infection, which causes neurosyphilis (NS) and at a later stage general paresis of the insane (GPI), present with brain pathology features of Alzheimer's disease (AD). However, the relationships among these illnesses regarding biomarker levels are still unclear. OBJECTIVE: To explore biomarker levels in NS and GPI compared with those in AD and the relationship between biomarker levels and cognitive function in NS and GPI. METHODS: Levels of neurogranin (NGRN) and ß-amyloid precursor protein cleaving enzyme (BACE1) in cerebrospinal fluid (CSF)/plasma, together with amyloid-ß 1-40 (Aß40), Aß42, and total tau in the CSF of 23 AD patients, 55 GPI patients, and 13 NS patients were measured. Patients were classified into none-to-mild, moderate, and severe stages of cognitive impairment. RESULTS: Levels of CSF NGRN, BACE1, and tau as well as plasma BACE1 levels were significantly different among groups. In the none-to-mild stage, plasma BACE1 levels correlated with the protein levels in CSF and were significantly increased in AD patients versus GPI patients. The CSF tau levels in AD patients were significantly increased versus GPI patients in the moderate and severe stages. Pooling data from GPI and NS patients, both CSF tau and plasma NGRN levels correlated with cognitive scale scores. CONCLUSION: GPI and NS patients might have different biomarker level patterns compared to AD patients. While plasma BACE1 could be a promising early biomarker for distinguishing AD from GPI, CSF tau and plasma NGRN levels might be valuable in indications of cognitive function in pooled NS populations.

Improving osteogenesis of calcium phosphate bone cement by incorporating with lysine: An in vitro study.

Calcium phosphate bone cement (CPC) has attracted extensive interests from surgeons and material scientists. However, its actual application is still limited because of its poor osteogenesis. In this work, lysine, one of the essential components of proteins, was incorporated into the CPC to improve its osteogenesis ability. Effects of lysine on the phase, morphology, physicochemical properties, protein adsorption, lysine release and cytocompatibility of CPC were investigated. Results showed that lysine had no significant influence on the phase and morphology of the hydrated cements, but evidently raised the compressive strength, apparent porosity and setting time of the cements in a content-dependent manner of lysine. In contrast to the control, the lysine-incorporated CPCs had notably enhanced in vitro osteogenesis capability. It was supposed to be synergistically attributed to the improvements of fibronectin (FN) anchoring and bone mesenchymal stem cells (BMSCs) adhesion on the hydrated cements as well as the sustained release of bioactive amino acid molecules. Hence, lysine was expected to be applied as a novel bioactive admixture in the development of CPC with the improved osteogenesis ability and physicochemical properties for numerous orthopedic applications.

Enhanced Osteogenesis of Injectable Calcium Phosphate Bone Cement Mediated by Loading Chondroitin Sulfate.

Toward repairing critical-sized bone defects, calcium phosphate cement (CPC) has been well recognized as a fairly promising bone graft because of its properties of injectability, self-setting, biocompatibility, and osteoconductivity. However, poor osteogenic capacity of CPC still limits its applications for meeting the demands of bone healing. In this work, chondroitin sulfate (CS), as an important component of the extracellular matrix network, was introduced into CPC to enhance its osteogenesis ability. Incorporation of CS had no evident effect on the phase, morphology, apparent porosity, and compressive strength of hydrated cement products, but it notably enhanced the injectability and improved the antiwashout property of the cement pastes. CS was able to be sustainably released from CS-CPCs in a CS-dose-dependent manner and supposed to have a long-term release potential for constant biological stimulation. CS-CPCs markedly accelerated the preferential adsorption of fibronectin. Furthermore, CS-CPCs significantly improved the adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells, which was synergistically mediated by the adhesion events of cells on the hydrated cements and the stimulation effects of CS molecules. Herein, utilization of CS is supposed to endow injectable calcium phosphate bone cements with enhanced osteogenic capacity and suitable physicochemical properties for numerous promising orthopedic applications.

Strontium ranelate simultaneously improves the radiopacity and osteogenesis of calcium phosphate cement.

In a minimally invasive surgery of osteoporotic fractures, high radiopacity is necessary to monitor the delivery and positioning of injectable cements and good osteogenesis is indispensable. In this work, strontium ranelate (SrR), an agent for treating osteoporosis, is firstly used as a radiopaque agent for calcium phosphate cement (CPC). The addition of SrR does not affect the hydration products of CPC, but prolonged the setting time and decreased the compressive strength. The injectability of the cement was higher than 85% when SrR content is more than 10 wt%. The radiopacity of CPC is significantly improved by SrR and higher than cortical bone when the content of SrR is more than 5 wt%. The concentration of Sr ions released from CPC is increased by the increasing content of SrR, which is among 17-1329 µM. Moreover, CPCs with SrR significantly promote the osteogenic differentiation of mouse bone marrow mesenchymal stem cells and inhibit the osteoclastogenic differentiation of RAW264.7 cells. Based on its good radiopacity and osteogenesis, suppressed osteoclastogenesis and appropriate physicochemical properties, the radiopaque CPC with more than 10 wt% SrR is prospective to be a promising biomaterial for osteoporotic fracture repairing in minimal invasive surgery.

Synthesis and Characterization of a Silica-Based Drug Delivery System for Spinal Cord Injury Therapy.

Acute inflammation is a central component in the progression of spinal cord injury (SCI). Anti-inflammatory drugs used in the clinic are often administered systemically at high doses, which can paradoxically increase inflammation and result in drug toxicity. A cluster-like mesoporous silica/arctigenin/CAQK composite (MSN-FC@ARC-G) drug delivery system was designed to avoid systemic side effects of high-dose therapy by enabling site-specific drug delivery to the spinal cord. In this nanosystem, mesoporous silica was modified with the FITC fluorescent molecule and CAQK peptides that target brain injury and SCI sites. The size of the nanocarrier was kept at approximately 100 nm to enable penetration of the blood-brain barrier. Arctigenin, a Chinese herbal medicine, was loaded into the nanosystem to reduce inflammation. The in vivo results showed that MSN-FC@ARC-G could attenuate inflammation at the injury site. Behavior and morphology experiments suggested that MSN-FC@ARC-G could diminish local microenvironment damage, especially reducing the expression of interleukin-17 (IL-17) and IL-17-related inflammatory factors, inhibiting the activation of astrocytes, thus protecting neurons and accelerating the recovery of SCI. Our study demonstrated that this novel, silica-based drug delivery system has promising potential for clinical application in SCI therapy.