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"Yan Li" was not included as an author in the original publication [...].
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In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells was investigated in C57BL/6J mice with PTX-induced neuropathic pain (PIPN). The particle size of EVs and CBD-EVs, surface roughness, nanomechanical properties, stability, and release studies were all investigated. To develop neuropathy in mice, PTX (8 mg/kg, i.p.) was administered every other day (four doses). In terms of decreasing mechanical and thermal hypersensitivity, CBD-EVs treatment was superior to EVs treatment or CBD treatment alone (p < 0.001). CBD and CBD-EVs significantly reduced mitochondrial dysfunction in dorsal root ganglions and spinal homogenates of PTX-treated animals by modulating the AMPK pathway (p < 0.001). Studies inhibiting the AMPK and 5HT1A receptors found that CBD did not influence the neurobehavioral or mitochondrial function of PIPN. Based on these results, we hypothesize that CBD and CBD-EVs mitigated PIPN by modulating AMPK and mitochondrial function.
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In this study we designed high-throughput 3D bioprinting of corneal equivalents which may address the need for in vitro models. In our digital 3D cornea model, average dimensions of adult cornea were converted to 3D shapes, then to G-code files which were printed by BIOX printer (CELLINK). To maintain the curvature of cornea, a support scaffold was designed using stereolithographic printer. The support scaffold could facilitate the printing of 6-12 corneas at a time thus enabling high-throughput printing. Human corneal keratocytes (HCKs) were incorporated in the optimized bio-ink, and cell-laden corneal stromal equivalents were printed. Printed structures were cross-linked by calcium chloride 100 mM, washed with Hanks' Balanced Salt Solution and incubated at 37°C in fibroblast media. Printed corneas were analyzed for live dead assay, Alamar assay, and expression of fibronectin and actin green markers. Printed corneas were able to maintain their structure, integrity, and clarity. Live dead assay and Alamar assay demonstrated that HCKs maintained high viability (>95%) for 2 weeks. HCKs in the printed corneas showed expression for fibronectin and actin green. In conclusion, high-throughput fabrication of 3D printed corneal stromal equivalents using a combination of stereolithography printing, extrusion based printing, and micro-transfer molding techniques was achieved.
