Biological and mechanical response of graphene oxide surface‐treated polylactic acid 3D‐printed bone scaffolds: experimental and numerical approaches

Employing 3D printing bone scaffolds with various polymers is growing due to their biocompatibility, biodegradability, and good mechanical properties. However, their biological properties need modification to have fewer difficulties in clinical experiments. Herein, the fused-deposition modeling technique is used to design triply-periodic-minimal-surfaces polylactic-acid scaffolds and evaluate their biological response under static and dynamic cell culture conditions. To enhance the biological response of 3D-printed bone scaffolds, graphene-oxide (GO) is coated on the surface of the scaffolds. Fourier-transform infrared spectroscopy, X-ray diffraction, and energy-dispersion X-ray analysis are conducted to check the GO presence and its effects. Also, computational fluid dynamics analysis is implemented to investigate the shear stress on the scaffold, which is a critical parameter for cell proliferation under dynamic cell culture conditions. Compression tests and contact-angle measurements are performed to assess the GO effect on mechanical properties and wettability, respectively. Also, it was shown that surface-treated scaffolds have lower mechanical properties and higher wettability than uncoated scaffolds. A perfusion bioreactor is used to study cell culture. Also, field-emission-scanning-electron-microscope and 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-tetrazolium-bromide (MTT) assay analyses are conducted to observe cell viability and cell attachment. An increase of up to 220% in viability was achieved with GO and dynamic cell culture

Formulation of nanoliposome-encapsulated bevacizumab (Avastin): Statistical optimization for enhanced drug encapsulation and properties evaluation

Bevacizumab (Avastin®), an anti-vascular endothelial growth factor, is one of the most effective drugs widely used to inhibit ocular angiogenesis. Nanoliposomes were recruited to improve the accessibility of bevacizumab (BVZ) during treatment. To optimize drug entrapment efficiency (DEE %), the effect of some independent variables was evaluated utilizing response surface methodology. The optimized formulation containing BVZ (NLP-BVZ) was characterized, and its safety was assessed. Employing arising retinal pigment epithelial (ARPE) cells, the permeability of the nanoliposome was analyzed. Structural stability and integrity of NLP-BVZ were also estimated with different methods. Optimal condition for the maximum DEE (39.9%) was obtained with cholesterol/DPPC (1,2-Dipalimitoyl-Sn-glycero-3-phosphocholine) (%w/w) 13.64, BVZ/DPPC (%w/w) 83.78 and 9 freeze–thaw cycles. Neutral fabricated NLP-BVZ with an average size of 141.5 ± 45.8 nm showed a smooth spherical structure and released the drug in a slow and sustained fashion. The formulation exhibited no obvious effect against human umbilical vein endothelial cells (HUVECs) and ARPEs. Additionally, the pattern of the circular dichroism (CD) and intrinsic fluorescence spectra confirmed the structural integrity of protein remained conserved after encapsulation. Taken together, the analysis indicated that the process of entrapment into nanoliposome meaningfully made the drug safer, more stable, and, therefore, appropriate for treating ocular disorde

The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease.

The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity. Both NLPs retard αSN fibrillization in a concentration-independent fashion. They do so largely by increasing lag time (formation of fibrillization nuclei) rather than elongation (extension of existing nuclei). Interactions between neutral NLPs and αSN may locate to the N-terminus of the protein. This interaction can even perturb the interaction of αSN with negatively charged NLPs which induces an α-helical structure in αSN. This interaction was found to occur throughout the fibrillization process. Both NLP-Chol and NLP-Chol-PEG were shown to be biocompatible in vitro, and to reduce αSN neurotoxicity and reactive oxygen species (ROS) levels with no influence on intracellular calcium in neuronal cells, emphasizing a prospective role for NLPs in reducing αSN pathogenicity in vivo as well as utility as a vehicle for drug delivery