Biology subjects

Brachi, G.

Publications and source records attributed to Brachi, G..

3 recordsLinked to original sources

bioRxiv2026

An injectable soft implant for long-acting, reversible, ultra-stable release of therapeutics

Providing long-term (>6 months) zero-order drug release from easily administered formulations is a key challenge in improving patient adherence and facilitating access. Herein, we report the design and development of an injectable, biodegradable, long-acting polymeric microparticle-embedded hydrogel platform for prolonged, zero-order release of therapeutics. This "soft implant" is injectable for ease of administration and can be retrieved via a small incision, allowing for discontinuation of therapy if desired. Central to the platform are surface-eroding poly(orthoester) (POE) microparticles, which were molecularly tailored to tune zero-order drug release across a wide range of timeframes. We demonstrate the clinical potential of the "soft implant" using levonorgestrel, a contraceptive agent requiring sustained dosing. In vitro, we observed zero-order release for 300 days, projected for >12 months, with behavior consistent with surface erosion further supported through Raman chemical mapping. In vivo studies confirmed zero-order release for six months, projected to 12 months, from a subcutaneous injection in rats. We envision that our platform could transform therapies that require long-term, regular drug dosing, significantly improving compliance and therapy outcomes.

bioengineering↗

bioRxiv2025

Chemical Stimulation Sustains Bioluminescence of Living Light Materials

Bioluminescence offers a powerful tool for real-time, label-free sensing for living materials. However, conventional approaches often rely on mechanical stimulation, which is difficult to standardize, spatially localize, and sustain over time. Here, we introduce a chemical strategy to stimulate and sustain bioluminescence in the marine dinoflagellate Pyrocystis lunula, enabling the fabrication of robust, adaptive, light-emitting living materials. By embedding P. lunula into 3D-printed, ionically crosslinked alginate hydrogel scaffolds, we engineered architecturally stable living materials with long-term cellular retention, viability, and light-emitting capacity. Exposure to acidic and basic environments enabled chemically resolved sensing and response via distinct bioluminescent signatures: acid triggers intense, localized, and persistent emission up to 25 minutes, while base induces a diffuse, biphasic emission indicative of cellular stress. Notably, coupling chemical with mechanical stimulation yields a synergistic enhancement of bioluminescence, achieving significantly greater amplitude and duration of light emission without compromising cell reactivity. Longitudinal studies over four weeks demonstrated that our living-light materials retain responsiveness and structural integrity across repeated stimulation cycles, overcoming the limitations of single-use mechanical activation. Together, these findings establish a robust new platform for programmable, light-emitting living materials with applications in biosensing, soft robotics, and environmental monitoring.

bioengineering↗

bioRxiv2024

Nanoscale biodegradable printing for designed tuneability of vaccine delivery kinetics

Two photon polymerization (2PP) 3D printing enables top-down biomaterial synthesis with nanoscale spatial resolution for de novo design of monodisperse injectable drug delivery systems. To address the limitations of current 2PP resins, we developed Spatiotemporal Controlled Release Inks of Biocompatible polyEsters (SCRIBE), a novel poly(lactic-co-glycolic acid)-triacrylate resin family with sub-micron resolution and tuneable hydrolysis. SCRIBE enables direct printing of hollow microparticles with tuneable chemistry and complex geometries inaccessible to molding techniques, which we use to engineer controlled protein release in vitro and in vivo. We use SCRIBE microparticles to modulate antibody titers and class switching as a function of antigen release rate and extend these findings to enable a single-injection vaccine formulation with extended antibody induction kinetics. Demonstrating how the chemistry and CAD of 2PP-printed microparticles can be used to tune responses to biomacromolecule release in vivo opens significant opportunities for a new generation of drug delivery vehicles. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/616252v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@a2e8c0org.highwire.dtl.DTLVardef@15ecbf1org.highwire.dtl.DTLVardef@9f734forg.highwire.dtl.DTLVardef@4b7e39_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗