Mechanical Property and Biocompatibility of PLLA Coated DCPD Composite Scaffolds

poster abstractIntroductions: Dicalcium phosphate dehydrate (DCPD) cements have been used for bone repair due to its excellent biocompatibility and resorability. However, DCPD cements are typically weak and brittleness. To address these limitations, the addition of sodium citrate as a regulator and polylactic acid (PLLA) as reinforcing agent has been proposed in this study. Objectives: 1) To develop composite PLLA/ DCPD scaffolds with enchanted toughness by PLLA coating. 2) To examine cell proliferation on the scaffolds. 3) To investigate the degradation behaviors of DCPD and PLLA/DCPD scaffolds. Materials and Methods: DCPD cements were synthesized with a 1:1 ratio of monocalcium phosphate monohydrate and -tricalcium phosphate with and without 100 mM sodium citrate in the mixing liquid. The specimens were prepared with powder to liquid ratio (P/L) of 1.00, 1.25 and 1.50. To fabricate the PLLA/DCPD composite scaffolds, DCPD scaffolds were coated with 5 % PLLA. The chemical and mechanical properties of DCPD scaffolds with and without PLLA coating after the in-vitro degradation (day 1, week 1, 4, and 6) were investigated by measuring their porosity, diametral tensile strength, and energy to fracture. In addition, cell adhesion and proliferation on these scaffolds were examined by scanning electron microscopy. Results: the addition of sodium citrate and the infiltration of PLLA significantly increased the mechanical properties of DCPD scaffolds (p < 0.05). The range of diametral tensile strength was 0.50-2.70 MPa and the range of energy to fracture was 0.80 to 9.90 N-mm. The most effective improvement of tensile strength and energy to fracture was achieved with P/L of 1.50. Moreover, incorporating PLLA to DCPD scaffolds slowed down the weight loss in the vitro degradation. Conclusion: a combination of template-casting and polymer impregnation methods can be applied to fabricate a cement/polymer biodegradable scaffold for bone tissue regeneration with significantly slow down degradation and excellent biocompatibility

A note on the stability of Toeplitz matrix inversion formulas

AbstractIn this paper, we consider the stability of the algorithms emerging from Toeplitz matrix inversion formulas. We show that if the Toeplitz matrix is nonsingular and well-conditioned, then they are numerically forward stable

Fabrication of Poly-l-lactic Acid/Dicalcium Phosphate Dihydrate Composite Scaffolds with High Mechanical Strength-Implications for Bone Tissue Engineering

Scaffolds were fabricated from poly-l-lactic acid (PLLA)/dicalcium phosphate dihydrate (DCPD) composite by indirect casting. Sodium citrate and PLLA were used to improve the mechanical properties of the DCPD scaffolds. The resulting PLLA/DCPD composite scaffold had increased diametral tensile strength and fracture energy when compared to DCPD only scaffolds (1.05 vs. 2.70 MPa and 2.53 vs. 12.67 N-mm, respectively). Sodium citrate alone accelerated the degradation rate by 1.5 times independent of PLLA. Cytocompatibility of all samples were evaluated using proliferation and differentiation parameters of dog-bone marrow stromal cells (dog-BMSCs). The results showed that viable dog-BMSCs attached well on both DCPD and PLLA/DCPD composite surfaces. In both DCPD and PLLA/DCPD conditioned medium, dog-BMSCs proliferated well and expressed alkaline phosphatase (ALP) activity indicating cell differentiation. These findings indicate that incorporating both sodium citrate and PLLA could effectively improve mechanical strength and biocompatibility without increasing the degradation time of calcium phosphate cement scaffolds for bone tissue engineering purposes

Effects of Bioactive Glass Scaffold and BMP-2 in Segmental Defects

poster abstractReconstruction of segmental defects in the load-bearing area has long been a challenge in orthopaedics. We have demonstrated the feasibility of a biodegradable load-bearing scaffold fabricated from poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2 (BMP-2) to successfully induce healing in those defects. However, there is limited osteoconduction observed with the PPF/TCP scaffold itself. Furthermore, a recent review on BMP-2 revealed greater risks in radiculities, ectopic bone formation, osteolysis and poor global outcome in association with the use of BMP-2 for spinal fusion. The aims of this study were to evaluate the potential use of a more osteoconductive material 13-93 bioactive glass and the potential side effects of locally delivered BMP-2 on adjacent bones. 13-93 glass scaffolds were fabricated by indirect selective laser sintering and implanted into critical size defects created in rat right femurs with and without 10 micrograms of BMP-2. The X-ray and micro-CT results showed that bridging callus was found as soon as 3 weeks and progressed gradually in the BMP group while minimal bone formation was observed in the control group. As expected, stiffness, peak load and energy to break of the BMP group were all higher than the control group. Higher healing rates in the 13-93 group was found compared to the healing rate in PPF/TCP group evaluated in the past indicating a more osteoconductive nature of the 13-93 scaffolds. The scaffolds of both control and BMP groups were partially degraded after 15 weeks as seen in the histological images. For the effects of local BMP-2 delivery to adjacent bones, no statistical difference in the bone area, mineral content and mineral density was found between control and BMP groups. In conclusion, a 13-93 bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its potential application in treating large bone defects

The Effect of Diluted Triple and Double Antibiotic Pastes on Dental Pulp Stem Cells and Established Enterococcus faecalis Biofilm

Objectives To investigate the effect of various dilutions of antibiotic medicaments used in endodontic regeneration on the survival of human dental pulp stem cells (DPSCs) and to determine their antibacterial effect against established Enterococcus faecalis biofilm. Materials and methods The cytotoxic and antibacterial effects of different triple (TAP) and double antibiotic paste (DAP) dilutions (0.125, 0.25, 0.5, 1, and 10 mg/ml) were tested against Enterococcus faecalis established biofilm and DPSC. Established bacterial biofilm were exposed to antibiotic dilutions for 3 days. Then, biofilms were collected, spiral plated, and the numbers of bacterial colony forming units (CFU/ml) were determined. For the cytotoxic effect, lactate dehydrogenase activity assays (LDH) and cell viability assays (WST-1) were used to measure the percentage of DPSC cytotoxicity after 3-day treatment with the same antibiotic dilutions. A general linear mixed model was used for statistical analyses (α = 0.05). Results All antibiotic dilutions significantly decreased the bacterial CFU/ml. For WST-1 assays, all antibiotic dilutions except 0.125 mg/ml significantly reduced the viability of DPSC. For LDH assays, the three lowest tested concentrations of DAP (0.5, 0.25, 0.125 mg/ml) and the two lowest concentrations of TAP (0.25 and 0.125 mg/ml) were non-toxic to DPSC. Conclusions All tested dilutions had an antibacterial effect against E. faecalis. However, 0.125 mg/ml of DAP and TAP showed a significant antibacterial effect with no cytotoxic effects on DPSCs. Clinical relevance Using appropriate antibiotic concentrations of intracanal medicament during endodontic regeneration procedures is critical to disinfect root canal and decrease the adverse effects on stem cells

The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors.

Deregulation of the phosphoinositide-3-OH kinase (PI(3)K) pathway has been implicated in numerous pathologies including cancer, diabetes, thrombosis, rheumatoid arthritis and asthma. Recently, small-molecule and ATP-competitive PI(3)K inhibitors with a wide range of selectivities have entered clinical development. In order to understand the mechanisms underlying the isoform selectivity of these inhibitors, we developed a new expression strategy that enabled us to determine to our knowledge the first crystal structure of the catalytic subunit of the class IA PI(3)K p110 delta. Structures of this enzyme in complex with a broad panel of isoform- and pan-selective class I PI(3)K inhibitors reveal that selectivity toward p110 delta can be achieved by exploiting its conformational flexibility and the sequence diversity of active site residues that do not contact ATP. We have used these observations to rationalize and synthesize highly selective inhibitors for p110 delta with greatly improved potencies

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study.

The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. Population-based retrospective cohort study. Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. Warfarin use within 14 days of IE diagnosis. Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage. [Abstract copyright: Copyright © 2023. Published by Elsevier Ltd.

Adaptation and psychometric evaluation of the Chinese version of the functional assessment of chronic illness therapy spiritual well-being scale among Chinese childhood cancer patients in China

BackgroundSpiritual well-being is a strength for childhood cancer patients to cope with cancer. The availability of a valid and reliable instrument for assessing spiritual well-being is crucial. This study translated and adapted the Functional Assessment of Chronic Illness Therapy Spiritual Well-being scale (FACIT-Sp) for Chinese childhood cancer patients and examined the psychometric properties and factor structure in this population.MethodsThis was a methodological study. The FACIT-Sp was translated into Chinese. Adaptation was based on our qualitative study. For psychometric evaluation, a convenience sample of 412 were recruited based on the suggested sample size for the exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Childhood cancer patients were included if they aged 8–17 years, with parental consent to participate, able to communicate that they were being treated for cancer, and able to communicate and read Chinese. Participants answered the Chinese version of the adapted FACIT-Sp, the Center for Epidemiology Studies Depression Scale for Children (CES-DC), and the Pediatric Quality of Life Inventory 3.0 Cancer Module (PedsQL). Content validity, convergent validity, internal consistency and test–retest reliability were examined. Both EFA and CFA assessed the structural validity of the adapted FACIT-Sp.ResultsThe content validity index values for items ranged 0.8–1.0 and that for the scale was 0.84, indicating appropriate content validity. The scale had good internal consistency, with a Cronbach’s alpha of 0.815. The FACIT-Sp scores positively correlated with the CES-DC scores, and negatively correlated with PedsQL scores, suggesting that the Chinese version of the adapted FACIT-Sp had reasonable convergent validity. EFA yielded a four-factor (meaning, peace, faith, and connection with others) model. The CFA results revealed that the four-factor model achieved a better fit than the original three-factor model (Chi-Square Mean/Degree of Freedom = 2.240 vs. 3.557, Comparative Fit Index = 0.953 vs. 0.916, Goodness of Fit Index = 0.909 vs. 0.884, Root Mean Square Error of Approximation = 0.078 vs. 0.112).ConclusionThe Chinese version of the adapted FACIT-Sp is a reliable and valid instrument for assessing spiritual well-being among Chinese childhood cancer patients. This instrument can be applied in clinical settings for routine assessment

The bracteatus pineapple genome and domestication of clonally propagated crops

Domestication of clonally propagated crops such as pineapple from South America was hypothesized to be a 'one-step operation'. We sequenced the genome of Ananas comosus var. bracteatus CB5 and assembled 513 Mb into 25 chromosomes with 29,412 genes. Comparison of the genomes of CB5, F153 and MD2 elucidated the genomic basis of fiber production, color formation, sugar accumulation and fruit maturation. We also resequenced 89 Ananas genomes. Cultivars 'Smooth Cayenne' and 'Queen' exhibited ancient and recent admixture, while 'Singapore Spanish' supported a one-step operation of domestication. We identified 25 selective sweeps, including a strong sweep containing a pair of tandemly duplicated bromelain inhibitors. Four candidate genes for self-incompatibility were linked in F153, but were not functional in self-compatible CB5. Our findings support the coexistence of sexual recombination and a one-step operation in the domestication of clonally propagated crops. This work guides the exploration of sexual and asexual domestication trajectories in other clonally propagated crops