1Biomaterial inks for extrusion-based 3D bioprinting: Property, classification, modification, and selection.

Three-dimensional (3D) extrusion-based bioprinting is the most widely used bioprinting technology to fabricate bionic tissue or organ constructs by combining biomaterial ink and living cells for tissue engineering and regenerative medicine. One critical issue of this technique is the selection of suitable biomaterial ink to simulate extracellular matrix (ECM) that provides mechanical support for cells and regulates their physiological activities. Previous studies have demonstrated that it is an enormous challenge to form and maintain reproducible 3D constructs and eventually achieve the balance among biocompatibility, mechanical properties, and printability. This review highlights the properties of extrusion-based biomaterial inks and recent developments as well as details various biomaterial inks classified by their function. Key approaches related to their modification methods according to the functional requirements are also discussed, along with the selection strategies by varying extrusion paths and methods in extrusion-based bioprinting. This systematical review will assist researchers in identifying the most suitable extrusion-based biomaterial inks based on their requirements, as well as in elaborating current challenges and prospects of extrudable biomaterial inks in the field of bioprinting of in vitro tissue models.

Effects of abnormal vertebral arteries and the circle of Willis on vertebrobasilar dolichoectasia: A multi-scale simulation study.

BACKGROUND: Vertebrobasilar dolichoectasia is a rare cerebrovascular disease characterized by obvious extension, dilation and tortuosity of vertebrobasilar artery, and its pathophysiological mechanism is not clear. This study focused on local hemodynamic changes in basilar arteries with typical vertebrobasilar dolichoectasia, together with unbalanced vertebral arteries and abnormal structures of the circle of Willis, through multi-scale modeling. METHODS: Three-dimensional models of 3 types of vertebrobasilar arteries were constructed from magnetic resonance images. The first type has no vertebrobasilar dolichoectasia, the second type has vertebrobasilar dolichoectasia and balanced vertebral arteries, and the third type has vertebrobasilar dolichoectasia and unbalanced vertebral arteries. A lumped parameter model of the circle of Willis was established and coupled to these three-dimensional models. FINDINGS: The results showed that unbalanced bilateral vertebral arteries, especially single vertebral artery deletion mutation, might associate with higher wall shear stress on anterior wall of basilar artery in patients with vertebrobasilar dolichoectasia. And unbalanced bilateral vertebral arteries would increase the blood pressure in basilar artery. Meanwhile, missing communicating arteries in the circle of Willis, especially bilateral posterior communicating arteries absences, would significantly increase blood pressure in basilar artery. The unilateral absence of posterior communicating arteries would increase differences in blood flow between the left and right posterior cerebral arteries. INTERPRETATION: This study provided a multi-scale modeling method and some preliminary results for helping understand the role of hemodynamics in occurrence and development of vertebrobasilar dolichoectasia.

Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2.

The outbreak of the 2019 novel coronavirus (SARS-CoV-2) has infected millions of people with a large number of deaths across the globe. The existing therapies are limited in dealing with SARS-CoV-2 due to the sudden appearance of the virus. Therefore, vaccines and antiviral medicines are in desperate need. We took immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein (S), membrane glycoprotein (M) and nucleocapsid protein (N) of SARS-CoV-2, followed by estimating their antigenicity and interactions with the human leukocyte antigen (HLA) alleles. Allergenicity, toxicity, physiochemical properties analysis and stability were examined to confirm the specificity and selectivity of the epitope candidates. We identified a total of five B cell epitopes in RBD of S protein, seven MHC class-I, and 18 MHC class-II binding T-cell epitopes from S, M and N protein which showed non-allergenic, non-toxic and highly antigenic features and non-mutated in 55,179 SARS-CoV-2 virus strains until June 25, 2020. The epitopes identified here can be a potentially good candidate repertoire for vaccine development.

An in vitro study of the influence of monocusp patch size on the hemodynamics for reconstructing right ventricular outflow tract in tetralogy of Fallot.

For relief of right ventricular outflow tract obstruction in the operative treatment of tetralogy of Fallot and other complex congenital heart disease, it is often necessary to perform transannular monocusp patch to prevent right ventricular pressure overload and reduce pulmonary regurgitation. But the the geometric relationship between a monocusp patch length and the size of RVOT is not well defined. Five 20 mm sized monocusp patches were tested in simulated RVOTs which sized from 18 mm to 22 mm at 1 mm interval, respectively. The hydrodynamics of the patches were assessed through a quasi-physiological artery pulsatile flow duplicator system. The transvalvular pressure difference, effective orifice area and regurgitation flow were determined. The results showed that the regurgitation fraction increased with the diameter of RVOT increased (from 6.25% at 18 mm RVOT to 26.63% at 22 mm RVOT). Implant an oversized monocusp patch in RVOT reconstruction can effectively decrease the regurgitation but increase the transvalvular pressure and may reduce the longevity of leaflet.

Mechanical properties of triply periodic minimal surface structures mimicking the microstructure of Woodpecker's cranial bone.

A new triply periodic minimal surface (TPMS) structure mimicking the microstructure of Great Spotted Woodpecker's cranial bone was designed, fabricated and tested in this study. It was found that the designed structures acquired better mechanical performance compared to the unit structures applied in heterogeneous porous scaffolds. The wall thickness mimicking the woodpecker's spongy bone and the TPMS surface structure were two contributors to the good mechanical performance of new designed bionic structures.

Ultrasound observation of GAG content of human hip joint cartilage in different old age groups.

In this study, we observed the age-related changes of glycosaminoglycan (GAG) content of human hip joint cartilage based on ultrasound (US). Seventy human hip cartilage-bone samples were collected from hip-fracture patients (ages 51 to 96) and divided into 5 groups (10 years in an age group). They were firstly measured by ultrasound to obtain quantitative acoustic parameters, including the speed of sound (SOS), US amplitude attenuation coefficient (UAA) and normalized broadband US attenuation coefficient (nBUA). Then the samples were stained for GAG with toluidine blue. Results showed SOS, UAA, nBUA decreased by 5.49%, 36.67%, 25.57% from 50-80 age group (p<;0.01), but increased by 0.34%, 1.19%, 5.23% in the 90 age group compared with the 80 age group, respectively. There were linear correlations between SOS and GAG optical density (r=0.825, p<;0.01), as well as UAA and GAG optical density (r=0.708, p <; 0.01). However, nBUA showed less significant linear correlation to GAG optical density (r=0.688, p <; 0.07). In summary, GAG content of hip joint cartilage varied with aging in elderly people and conventional ultrasound can potentially be used to detect the age-related changes of acoustic parameters of human hip joint cartilage.

Correlations between X-ray attenuation and GAG content of different cartilage layers based on contrast agent enhanced Micro-CT.

OBJECTIVES: To build the quantitative relationships between X-ray attenuation and glycosaminoglycan (GAG) content of different layers of progressive trypsin digested articular cartilage (AC) models based on the contrast agent enhanced Micro-CT. METHODS: Bovine AC samples were treated with 0.5% concentration of trypsin for different degeneration time, immersed in contrast agent and then scanned by Micro-CT to obtain the X-ray attenuation. Combining with histological analysis, the relationships between the X-ray attenuation and GAG optical density of the superficial and middle layer were analyzed. RESULTS: The X-ray mean attenuation increased about 16.48% (p<;0.01) in the superficial layer within the first 10-minute degeneration, 26.99% (p<;0.05) in the middle layer within the first 40-minute degeneration, but merely changed in the deep layer in the entire experiment. Contrary to the change of X-ray mean attenuation, the GAG optical density decreased from 31.98±13.00 to 11.69±4.23 (p<;0.01) in the superficial layer within the first 10-minute degeneration, from 82.94±7.35 to 3.85±3.31 (p<;0.01) in the middle layer within the entire degeneration and didn't slightly decrease from 96.10±2.50 to 91.45±1.90 (p<;0.05) until the last 10-minute degeneration in deep layer. In addition, the changes of the X-ray mean attenuation showed negative linear correlations with the GAG content in the superficial (r = -0.984, p<;0.01) and the middle layer (r = -0.960, p<;0.01), respectively. CONCLUSION: The contrast agent enhanced Micro-CT can elucidate the variation of GAG content in trypsin-induced progressive AC models by X-ray mean attenuation of different cartilage layers.