Designer Extracellular Vesicles Modulate Pro-Neuronal Cell Responses and Improve Intracranial Retention.

Gene/oligonucleotide therapies have emerged as a promising strategy for the treatment of different neurological conditions. However, current methodologies for the delivery of neurogenic/neurotrophic cargo to brain and nerve tissue are fraught with caveats, including reliance on viral vectors, potential toxicity, and immune/inflammatory responses. Moreover, delivery to the central nervous system is further compounded by the low permeability of the blood brain barrier. Extracellular vesicles (EVs) have emerged as promising delivery vehicles for neurogenic/neurotrophic therapies, overcoming many of the limitations mentioned above. However, the manufacturing processes used for therapeutic EVs remain poorly understood. Here, we conducted a detailed study of the manufacturing process of neurogenic EVs by characterizing the nature of cargo and surface decoration, as well as the transfer dynamics across donor cells, EVs, and recipient cells. Neurogenic EVs loaded with Ascl1, Brn2, and Myt1l (ABM) are found to show enhanced neuron-specific tropism, modulate electrophysiological activity in neuronal cultures, and drive pro-neurogenic conversions/reprogramming. Moreover, murine studies demonstrate that surface decoration with glutamate receptors appears to mediate enhanced EV delivery to the brain. Altogether, the results indicate that ABM-loaded designer EVs can be a promising platform nanotechnology to drive pro-neuronal responses, and that surface functionalization with glutamate receptors can facilitate the deployment of EVs to the brain.

A Comparative Study of Braided versus Barbed Suture for Cystotomy Repair.

BACKGROUND: In this study, we aim to compare outcomes after cystotomy repair between standard sutures (910 polyglactin, poliglecaprone) versus barbed (V-LocTM 90) suture. As a secondary outcome, we analyzed factors for suture preference between the two groups. METHODS: A retrospective chart review was undertaken for surgeries complicated by cystotomy, identified by ICD-9/10 codes from 2016 to 2019 at West Virginia University (WVU) Hospital. Comparisons were made between cystotomy repair using barbed suture versus standard braided suture. Injuries were categorized by procedure, surgical route, type of suture used in repair, and subsequent complications related to repair. Primary endpoints were examined by Pearson's Chi-square test and interval data by t-test. A p < 0.05 was significant. RESULTS: Sixty-eight patients were identified with iatrogenic cystotomy at WVU. Barbed suture was used for cystotomy repair in 11/68 (16.2%) patients. No significant difference was seen in postoperative outcomes between patients repaired with barbed suture versus standard braided suture. Barbed suture was significantly more likely to be used for cystotomy repair in minimally invasive surgery (p = 0.001). It was most often utilized in a robotic approach 7/11 (63.6%) followed by laparoscopic 3/11 (27.3%). Body mass index (BMI) was significantly higher in patients receiving a barbed suture repair (p = 0.005). CONCLUSION: Barbed suture may be comparable to standard braided suture for cystotomy repair. Barbed suture may offer a practical alternative to facilitate cystotomy repair in minimally invasive surgery, especially in patients with a high BMI.

Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue.

Although cellular therapies represent a promising strategy for a number of conditions, current approaches face major translational hurdles, including limited cell sources and the need for cumbersome pre-processing steps (for example, isolation, induced pluripotency). In vivo cell reprogramming has the potential to enable more-effective cell-based therapies by using readily available cell sources (for example, fibroblasts) and circumventing the need for ex vivo pre-processing. Existing reprogramming methodologies, however, are fraught with caveats, including a heavy reliance on viral transfection. Moreover, capsid size constraints and/or the stochastic nature of status quo approaches (viral and non-viral) pose additional limitations, thus highlighting the need for safer and more deterministic in vivo reprogramming methods. Here, we report a novel yet simple-to-implement non-viral approach to topically reprogram tissues through a nanochannelled device validated with well-established and newly developed reprogramming models of induced neurons and endothelium, respectively. We demonstrate the simplicity and utility of this approach by rescuing necrotizing tissues and whole limbs using two murine models of injury-induced ischaemia.