Biology subjects

Hassan, L. F.

Publications and source records attributed to Hassan, L. F..

4 recordsLinked to original sources

bioRxiv2026

Profiling and modulating astrocyte borders at injected biomaterials in mice

Astrocyte border formation is a conserved neuroprotective response to neural tissue disruption, yet astrocyte border states at implanted biomaterials remain less well characterized than injury responses. Here, we developed the Astrocyte Border Characterization (ABC) Tool, which leverages a shear-thinning, injectable biomaterial to locally deliver astrocyte-specific RiboTag AAVs and small molecule regulators in the mouse striatum, enabling molecular profiling and phenotypic modulation of astrocyte border (AB) cells. Spatially precise delivery of AAV using the ABC Tool yielded enhanced specificity and robust RiboTag expression in AB cells from 7-70 days post injection. Temporal transcriptomic profiling of AB cells revealed predominantly acute, transient changes in genes governing dedifferentiation, proliferation, metabolic reprogramming, and inflammation regulation. Persistent changes accounted for only 14% of regulated genes but involved critical gain of functions in immune regulation and host defense that mirrored astrocyte border responses at chronic CNS injuries. Local delivery of indiscriminate or astrocyte-selective ablation molecules delayed, rather than prevented, border formation, ultimately yielding thicker astrocytes borders with increased inflammation and fibrosis at the biomaterial-tissue interface. Conversely, local delivery of {beta}-hydroxybutyrate (BHB) from the ABC Tool altered key aspects of the transcriptional reprogramming to attenuate chronic astrocyte reactivity and prevent biomaterial contraction without exacerbating inflammation or fibrosis. Our findings establish the ABC Tool as a bioassay for studying and manipulating astrocyte borders at implanted biomaterials and identify focal metabolic regulation as a strategy to modulate AB cell phenotypes and enhance the CNS biocompatibility of biomaterials.

neuroscience↗

bioRxiv2026

Predicting recovery trajectories and injury severity following partial crush spinal cord injury in mice

The partial crush spinal cord injury (SCI) model enables preclinical testing of experimental therapies in mice, but substantial inter-animal variability in recovery outcomes confounds efficacy assessments. Here, we used open field behavioral data collected during the first 3 days post partial thoracic SCI to generate an Acute Functional Score (AFS) that defined three subgroups with divergent recovery trajectories. Applying latent class growth analysis and growth mixture modeling to open field and grid walk testing data, we demonstrated 83-92% prediction accuracy for AFS-defined recovery trajectories. The three subgroups differed significantly in treadmill kinematics and histological assessments of lesion size and astrocyte bridging. Applying the recovery trajectory framework to mice receiving saline or biomaterial vehicle injections at 3 days post-SCI revealed robust predictive accuracy while exposing disproportionate injury severity distributions between experimental groups. The approach enables individualized post-SCI recovery characterization that can neutralize procedural bias, minimize animal numbers, and provide a probabilistic basis for evaluating whether interventions enhance or suppress wound repair processes. Our findings establish a foundation for improving preclinical SCI study design and accelerating identification of effective therapies.

neuroscience↗

bioRxiv2024

Thioether-functionalized cellulose for the fabrication of oxidation-responsive biomaterial coatings and films

Biomaterial coatings and films can prevent premature failure and enhance performance of chronically implanted medical devices. However, current hydrophilic polymer coatings and films have significant drawbacks, including swelling and delamination. To address these issues, we modified hydroxyethyl cellulose with thioether groups to generate an oxidation-responsive polymer, HECMTP. HECMTP readily dissolves in green solvents and can be fabricated as coatings or films with tunable thicknesses. HECMTP coatings effectively scavenge hydrogen peroxide, resulting in conversion of thioether groups to sulfoxide groups on the polymer chain. Oxidation-driven, hydrophobic-to-hydrophilic transitions that are isolated to the surface of HECMTP coating under physiologically relevant conditions increase wettability, decrease stiffness, and reduce protein adsorption to generate a non-fouling interface with minimal coating delamination or swelling. HECMTP can be used in diverse optical applications and permits oxidation-responsive, controlled drug release. HECMTP films are non-resorbable in vivo and evoke minimal foreign body responses. These results highlight the versatility of HECMTP and support its incorporation into chronically implanted medical devices.

bioengineering↗

bioRxiv2023

Trehalose-based coacervates for local bioactive protein delivery to the central nervous system

Therapeutic outcomes of local biomolecule delivery to the central nervous system (CNS) using bulk biomaterials are limited by inadequate drug loading, neuropil disruption, and severe foreign body responses. Effective CNS delivery requires addressing these issues and developing well-tolerated, highly-loaded carriers that are dispersible within local neural parenchyma. Here, we synthesized biodegradable trehalose-based polyelectrolyte oligomers using facile A2:B3:AR thiol-ene Michael addition reactions that form complex coacervates upon mixing of oppositely charged oligomers. Coacervates permit high concentration loading and controlled release of bioactive growth factors, enzymes, and antibodies, with modular formulation parameters that confer tunable release kinetics. Coacervates are cytocompatible with cultured neural cells in vitro and can be formulated to either direct intracellular protein delivery or sequester media containing proteins and remain extracellular. Coacervates serve as effective vehicles for precisely delivering biomolecules, including bioactive neurotrophins, to the mouse striatum following intraparenchymal injection. These results support the use of trehalose-based coacervates as part of therapeutic protein delivery strategies for CNS disorders.

bioengineering↗