Retinal nerve fiber layer thickness is associated with hippocampus and lingual gyrus volumes in nondemented older adults.

OBJECTIVES: Abnormal retina structures, such as thinner retinal nerve fiber layer (RNFL), have been frequently reported in patients with Alzheimer's disease (AD). However, the association between RNFL and brain structures in cognitively normal adults remains unknown. We therefore set out to conduct a cross-sectional investigation to determine whether RNFL thickness is associated with brain structure volumes in nondemented older adults. METHODS: We measured RNFL thickness by optical coherence tomography and brain structure volumes by 3 T magnetic resonance imaging. Cognitive function was assessed using the Chinese version of Repeatable Battery for the Assessment of Neurological Status. Pearson correlation was initially employed to screen for the potential associations among RNFL thickness, brain structure volumes and cognitive function. And then, multivariable linear regression models were conducted to further examine such associations adjusting for possible confounding factors, including age, sex, years of education and the estimated total intracranial volume (eTIV). RESULTS: 113 participants (≥ 65 years old) were screened and 80 of them (mean age: 68 ± 5.3 years; 48% male) were included in the final analysis. RNFL thickness in temporal quadrant was associated with medial temporal lobes volumes [unadjusted: r = 0.155, P = 0.175; adjusted: ß = 0.205 (0.014, 0.383), P = 0.035], and especially associated with the hippocampus volume [unadjusted: r = 0.213, P = 0.062; adjusted: ß = 0.251 (0.060, 0.435), P = 0.011] after adjusted for age, sex, years of education and eTIV. Moreover, it showed that RNFL thickness in inferior quadrant [unadjusted: r = 0.221, P = 0.052; adjusted: ß = 0.226 (0.010. 0.446), P = 0.041] was significantly associated with occipital lobes volumes after the adjustment of age, sex, years of education and eTIV, and selectively associated with the substructure of lingual gyrus volume [unadjusted: r = 0.223, P = 0.050; adjusted: ß = 0.278 (0.058, 0.487), P = 0.014]. In addition, average RNFL thickness was associated with the cognitive domain of visuospatial/constructional [unadjusted: r = 0.114, P = 0.322; adjusted: ß = 0.216 (0.006, 0.426), P = 0.044] after the adjustment in these nondemented older adults. CONCLUSIONS: Quadrant-specific associations exist between RNFL thickness and brain regions vulnerable to aging or neurodegeneration in older adults with normal cognition. These findings would promote further investigations into using RNFL as a noninvasive and less expensive biomarker of neurocognitive aging and AD-related neurodegeneration.

Retinal Nerve Fiber Layer Thinning Is Associated With Brain Atrophy: A Longitudinal Study in Nondemented Older Adults.

Backgrounds: Abnormal retinal nerve fiber layer (RNFL) thickness has been observed in patients with Alzheimer's disease (AD) and therefore suggested to be a potential biomarker of AD. However, whether the changes in RNFL thickness are associated with the atrophy of brain structure volumes remains unknown. We, therefore, set out a prospective investigation to determine the association between longitudinal changes of RNFL thickness and brain atrophy in nondemented older participants over a period of 12 months. Materials and Methods: We measured the RNFL thickness using optical coherence tomography (OCT) and brain structure volumes by 3T magnetic resonance imaging (MRI) before and after 12 months. Cognitive function was assessed using the Chinese version of Mini-Mental State Examination (CMMSE) and Repeatable Battery for the Assessment of Neurological Status. Associations among the changes of RNFL, brain structures and cognitive function were analyzed with Spearman correlation and multiple linear regression models adjusting for the confounding factors. Results: Fifty old participants were screened and 40 participants (mean age 71.8 ± 3.9 years, 60% were male) were enrolled at baseline. Among them, 28 participants completed the follow-up assessments. The average reduction of RNFL thickness was inversely associated with the decrease of central cingulate cortex volume after the adjustment of age and total intracranial volume (ß = -0.41, P = 0.039). Specifically, the reduction of RNFL thickness in the inferior, not other quadrants, was independently associated with the decline of central cingulate cortex volume after the adjustment (ß = -0.52, P = 0.006). Moreover, RNFL thinning, central cingulate cortex atrophy and the aggregation of white matter hyperintensities (WMH) were found associated with episodic memory in these older adults with normal cognition. Conclusions: RNFL thinning was associated with cingulate cortex atrophy and episodic memory decline in old participants. The longitudinal changes of RNFL thickness are suggested to be a useful complementary index of neurocognitive aging or neurodegeneration.

A facile method for the preparation of chitosan-based scaffolds with anisotropic pores for tissue engineering applications.

To date, great efforts have been made to prepare different kinds of isotropic tissue engineering (TE) scaffolds. However, little attention has been paid to anisotropic porous scaffolds in spite of many examples of their excellent performances. In this work, a facile method termed "ammonia-induced method" (AIM) was proposed and applied to generate anisotropic pores in chitosan (CS)-based scaffolds. The pore structures of these scaffolds were studied in detail. In order to clarify the rationale behind this process, a speculative explanation was provided on basis of the experimental results and the theory of Uras (Uras & Devlin, 2000). Compression tests indicated that the mechanical strengths of these scaffolds were sufficient for TE applications. In vitro cell culture showed that MC3T3-E1 cells cultivated in the pores of these scaffolds had positive proliferation potential. We anticipated that this novel AIM could inspire research not only in TE but also in other fields.

A novel chitosan-tussah silk fibroin/nano-hydroxyapatite composite bone scaffold platform with tunable mechanical strength in a wide range.

Currently, great efforts have been made to enhance the mechanical strength of bone tissue engineering (BTE) scaffolds, which are composed of biopolymeric matrices and inorganic nano-fillers. But the tunability of mechanical strength in a wide range for BTE scaffolds has seldom been investigated in spite of the great importance of this performance. In this work, a chitosan-tussah silk fibroin/hydroxyapatite (CS-TSF/HAp) hydrogel was synthesized by using a novel in situ precipitation method. Through in situ inducing the conformation transition of TSF in the CS-TSF/HAp hydrogel, which could be monitored by XRD, FT-IR, TGA, and DTA, the elastic modulus and fracture strength of the final CS-TSF/HAp composite could be tailored in a wide range without changing its composition, morphology, roughness, and crystal structures. The elastic modulus of the CS-TSF/HAp composite ranged from ∼250 to ∼400MPa while its fracture strength ranged from ∼45 to ∼100MPa. In order to clarify the rationale behind this process, a speculative explanation was provided. In vitro cell culture indicated that MC3T3-E1 cells cultured on the CS-TSF/HAp composite had positive adhesion, proliferation, and differentiation potential. We believed that the CS-TSF/HAp composite could be used as an ideal scaffold platform for cell culture and implantation of bone reconstruction.

Carboxylated Agarose (CA)-Silk Fibroin (SF) Dual Confluent Matrices Containing Oriented Hydroxyapatite (HA) Crystals: Biomimetic Organic/Inorganic Composites for Tibia Repair.

By in situ combining the dual cross-linking matrices of the carboxylated agarose (CA) and the silk fibroin (SF) with the hydroxyapatite (HA) crystals, the CA-SF/HA composites with optimal physicochemical and biological properties were obtained, which were designed to meet the clinical needs of load-bearing bone repair. With the synergistic modulation of the dual organic matrices, the HA nanoparticles presented sheet and rod morphologies due to the preferred orientation, which successfully simulated the biomineralization in nature. The chemical reactivity of the native agarose (NA) was significantly enhanced via carboxylation, and the CA exhibited higher thermal stability than the NA. In the presence of SF, the composites showed optimal mechanical properties that could meet the standard of bone repair. The degradation of the composites in the presence of CA and SF was significantly delayed such that the degradation rate of the implant could satisfy the growth rate of the newly formed bone tissue. The in vitro tests confirmed that the CA-SF/HA composite scaffolds enabled the MG63 cells to proliferate and differentiate well, and the CA/HA composite presented greater capability of promoting the cell behaviors than the NA/HA composite. After 24 days of implantation, newly formed bone was observed at the tibia defect site and around the implant. Extensive osteogenesis was presented in the rats treated with the CA-SF/HA composites. In general, the CA-SF/HA composites prepared in this work had the great potential to be applied for repairing large bone defects.

A detailed study of homogeneous agarose/hydroxyapatite nanocomposites for load-bearing bone tissue.

Agarose/hydroxyapatite (agar/HA) nanocomposites for load-bearing bone substitutes were successfully fabricated via a novel in situ precipitation method. Observation via SEM and TEM revealed that the spherical inorganic nanoparticles of approximately 50 nm were well dispersed in the organic matrix, and the crystallographic area combined closely with the amorphous area. The uniform dispersion of HA nanoparticles had prominent effect on improving the mechanical properties of the agar/HA nanocomposites (the highest elastic modulus: 1104.42 MPa; the highest compressive strength: 400.039 MPa), which proved to be potential load-bearing bone substitutes. The thermal stability of agarose and nanocomposites was also studied. The MG63 osteoblast-like cells on the composite disks displayed fusiform and polygonal morphology in the presence of HA, suggesting that the cell maturation was promoted. The results of cell proliferation and cell differentiation indicated that the cells cultured on the agar/HA composite disks significantly increased the alkaline phosphatase activity and calcium deposition. The structural role of agarose in the composite system was investigated to better understand the effect of biopolymer on structure and properties of the composites. The optimal properties were the result of a comprehensive synergy of the components.

Biomineralization-inspired synthesis of chitosan/hydroxyapatite biocomposites based on a novel bilayer rate-controlling model.

In order to prepare sophisticated biomaterials using a biomimetic approach, a deeper understanding of biomineralization is needed. Of particular importance is the control and regulation of the mineralization process. In this study, a novel bilayer rate-controlling model was designed to investigate the factors potentially influencing mineralization. In the absence of a rate-controlling layer, nano-scale hydroxyapatite (HA) crystallites exhibited a spherical morphology, whereas, in the presence of a rate-controlling layer, HA crystallites were homogeneously dispersed and spindle-like in structure. The mineralization rate had a significant effect on controlling the morphology of crystals. Furthermore, in vitro tests demonstrated that the reaction layer containing spindle-like HA crystallites possessed superior biological properties. These results suggest that a slow mineralization rate is required for controlling the morphology of inorganic crystallites, and consumption by the rate-controlling layer ensured that the ammonia concentration remained low. This study demonstrates that a biomimetic approach can be used to prepare novel biomaterials containing HA crystallites that have different morphologies and biological properties.

Characterization of calcium carbonate crystals in pigeon yolk sacs with different incubation times.

Calcium carbonate crystals are known to form in the yolk sacs of fertile pigeon eggs at late stages of incubation. The composition and structure of these crystals were investigated, the crystallization environment was inspected, and the physical chemistry constants of the yolk fluid were determined through the incubation period. Polarized light microscopy was used to observe the generation and distribution of calcium carbonate crystals in the yolk sac. In addition, X-ray diffraction was employed to analyze the composition and crystal phase of the yolk sac. A decalcification and deproteination method was established to analyze the ultrastructure and composition of the crystals, as well as the internal relationship between inorganic and organic phases of the crystals. Additionally, scanning electron microscopy, transmission electron microscopy, X-ray energy dispersive spectroscopy, and Fourier transform infrared spectroscopy were used to evaluate the characteristics of the crystals. Our results demonstrated that the calcium carbonate crystals were mainly composed of vaterite and calcite, with vaterite being the major component. Vaterite, a type of biomaterial generated by an organic template control, presented as a concentric hierarchical spherical structure. The organic nature of the biomaterial prevented vaterite from transforming into calcite, which is more thermodynamically stable than vaterite. Additionally, the configuration, size, and aggregation of vaterite were also mediated by the organic template. This bio-vaterite was found during the incubation period and is valuable in calcium transport during embryonic development.

Preparation and evaluation of collagen-silk fibroin/hydroxyapatite nanocomposites for bone tissue engineering.

A new in situ precipitation technique was developed to synthesize collagen-silk fibroin/hydroxyapatite nanocomposites. The componential properties and morphological of nanocomposites were investigated. It was revealed that the inorganic phase in the nanocomposite was carbonate-substituted hydroxyapatite with low crystallinity. Morphology studies showed that hydroxyapatite particles with size ranging from 30 to 100 nm were distributed uniformly in the polymer matrix. According to the TEM micrographs, inorganic particles were composed of more fine sub-particles whose diameters were between 2 and 5 nm in size without regular crystallographic orientation. The mechanical properties of the composites were evaluated by measuring their elastic modulus. The data indicated that the elastic modulus of nanocomposites was improved by the addition of silk fibroin. Finally, the cell biocompatibility of the composites was tested in vitro, which showed that they have good biocompatibility. These results suggest that the collagen-silk fibroin/hydroxyapatite nanocomposites are promising biomaterials for bone tissue engineering.

Synthesis and characterization of chitosan-multiwalled carbon nanotubes/hydroxyapatite nanocomposites for bone tissue engineering.

Chitosan-multiwalled carbon nanotubes/hydroxyapatite nanocomposites were synthesized by a novel in situ precipitation method. The electrostatic adsorption between multiwalled carbon nanotubes and chitosan was investigated and explained by Fourier transform infrared spectroscopy analysis. Morphology studies showed that uniform distribution of hydroxyapatite particles and multiwalled carbon nanotubes in the polymer matrix was observed. In chitosan-multiwalled carbon nanotubes/hydroxyapatite nanocomposites, the diameters of multiwalled carbon nanotubes were about 10 nm. The mechanical properties of the composites were evaluated by measuring their compressive strength and elastic modulus. The elastic modulus and compressive strength increased sharply from 509.9 to 1089.1 MPa and from 33.2 to 105.5 MPa with an increase of multiwalled carbon/chitosan weight ratios from 0 to 5 %, respectively. Finally, the cell biocompatibility of the composites was tested in vitro, which showed that they have good biocompatibility. These results suggest that the chitosan-multiwalled carbon nanotubes/hydroxyapatite nanocomposites are promising biomaterials for bone tissue engineering.