Biology subjects

Abundo, M. P.

Publications and source records attributed to Abundo, M. P..

3 recordsLinked to original sources

bioRxiv2024

Ultrasound-actuated drug delivery with acoustic percolation switches

Devices that can be remote-controlled under image guidance to precisely deliver biomedicines to sites of disease are a major goal of biomedical research. However, most existing externally triggered delivery systems are based on complex micromachines that are controlled with electromagnetic waves and require custom external instrumentation. Here we present a drug delivery platform comprising a simple protein-containing hydrogel that can be both imaged and triggered to release drugs at specific locations using widely available ultrasound imaging devices. This technology is based on the addition of air-filled protein nanostructures called gas vesicles (GVs) to hydrogel delivery vehicles. While intact, GVs sterically block the release of drug payloads and allow the vehicle to be imaged with ultrasound. An increase in ultrasound pressure causes the collapse of GVs within hydrogels present at the desired anatomical location, instantly creating percolation channels and triggering rapid drug release. Both the imaging and release are performed using a common diagnostic ultrasound probe. We implement this concept by establishing ultrasound-controlled drug diffusion and release from hydrogels in vitro and demonstrating targeted image-guided protein delivery in vivo following oral administration. We use this approach to deliver anti-inflammatory antibodies to treat gastrointestinal inflammation in a rat model of colitis. Targeted acoustic percolation switches (TAPS) open a conduit for local, image-guided drug delivery with a simple formulation and commonplace ultrasound equipment.

bioengineering↗

bioRxiv2022

Smart sealants for prevention and monitoring of gastrointestinal anastomotic leaks using portable smartphone-controlled ultrasound transducers

Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of the cases. Penetration of digestive fluids into the peritoneal cavity may lead to dreadful complications, including sepsis and premature death. Modern suture supports and tissue adhesives only insufficiently address the issue. Due to the scarcity of alternatives, surgeons rely on monitoring surrogate markers and clinical symptoms, which oftentimes lack sensitivity and specificity, hence only offering late-stage detection of already fully developed leaks. Here, a first-of-its-kind, modular, intelligent suture support patch capable of sealing and monitoring leaks under harsh gastrointestinal conditions is presented. The smart adhesive layered hydrogel patch provides, in addition to unprecedented tissue sealing under most demanding conditions, unique leak-detection capabilities based on pH and/or enzyme-responsive sensing elements, which can be read out by non-invasive point-of-need ultrasound imaging. Reliable detection of the breaching of sutures in as little as 3 hours in intestinal leak and 15 minutes in gastric leak conditions, and before an actual leak develops, is demonstrated. This technology paves the way for next-generation suture support materials that offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables. SummaryElectronic-free smart surgical hydrogel sealants leveraging tissue-penetrating polymer networks and trigger-responsive echogenic entities to enable point-of-need monitoring and early anastomotic leak detection using a hand-held ultrasound transducer and a smartphone.

bioengineering↗

bioRxiv2019

Genetically encoded nanostructures enable acoustic manipulation of engineered cells

The ability to mechanically manipulate and control the spatial arrangement of biological materials is a critical capability in biomedicine and synthetic biology. Ultrasound has the ability to manipulate objects with high spatial and temporal precision via acoustic radiation force, but has not been used to directly control biomolecules or genetically defined cells. Here, we show that gas vesicles (GVs), a unique class of genetically encoded gas-filled protein nanostructures, can be directly manipulated and patterned by ultrasound and enable acoustic control of genetically engineered GV-expressing cells. Due to their differential density and compressibility relative to water, GVs experience sufficient acoustic radiation force to allow these biomolecules to be moved with acoustic standing waves, as demonstrated within microfluidic devices. Engineered variants of GVs differing in their mechanical properties enable multiplexed actuation and act as sensors of acoustic pressure. Furthermore, when expressed inside genetically engineered bacterial cells, GVs enable these cells to be selectively manipulated with sound waves, allowing patterning, focal trapping and translation with acoustic fields. This work establishes the first genetically encoded nanomaterial compatible with acoustic manipulation, enabling molecular and cellular control in a broad range of contexts.

bioengineering↗