Biology subjects

Che, S.

Publications and source records attributed to Che, S..

3 recordsLinked to original sources

bioRxiv2025

Polysialic Acid Presentation on Microporous Scaffolds Supports Neural Repair after Ischemic Stroke

Recovery following ischemic stroke remains limited due to insufficient neural regeneration. Polysialic acid (PSA), a glycan prominently expressed during neural development, modulates neural progenitor cell (NPC) plasticity and migration, but its therapeutic potential in biomaterial-based stroke therapies remains underexplored. In this study, microporous annealed particle (MAP) scaffolds conjugated with PSA (PSA-MAP) were engineered to regulate NPC fate and promote neural tissue regeneration after stroke. PSA-MAP increased the presence of Sox2-positive progenitor cells within infarct and peri-infarct regions and elevated axonal content (NF200) in the lesion, while astrocytic and vascular coverage were not detectably changed at this early stage. In addition, 3D NPC cultures in MAP showed that tethered PSA alters NPC behavior over time, with reduced progenitor marker expression and PSA-dependent shifts in morphology, consistent with progression away from a progenitor state. Together, these data identify a glycan-forward, neuro-first repair route in which PSA-MAP enhances early neural regeneration without requiring concomitant angiogenic expansion, establishing PSA-MAP as a targeted biomaterial approach for endogenous neural repair after ischemic stroke.

bioengineering↗

bioRxiv2025

Polysialic Acid-Functionalized MAP Scaffolds Promote Regulatory Immune Responses After Ischemic Stroke

Glycosylation regulates immune and neural functions within the central nervous system (CNS), yet biomaterials rarely leverage glycans due to their structural complexity. Polysialic acid (PSA), comprising 2,8-linked sialic acid residues, is a promising candidate owing to its potent immunomodulatory interactions with inhibitory Siglec receptors. Systematic screening of multiple sialic acid derivatives identifies PSA as uniquely effective in inducing anti-inflammatory polarization of bone marrow-derived macrophages (BMDMs). Based on these findings, an injectable microporous annealed particle (MAP) scaffold presenting PSA covalently via its reducing end (MAP-PSA) is engineered, recapitulating physiological glycan orientation. MAP-PSA exhibits robust mechanical properties, stable glycan immobilization, and resistance to enzymatic degradation. Using ischemic stroke as a CNS injury model, MAP-PSA significantly reduces neutrophil infiltration and inflammatory activation while enhancing reparative macrophage and microglial phenotypes. These immunomodulatory effects persist into subacute stages, characterized by sustained reductions in inflammation and enhanced microglial homeostasis. Overall, MAP-PSA scaffolds demonstrate a novel therapeutic paradigm for CNS injuries such as stroke, with translational potential for broader neuroinflammatory and regenerative applications.

bioengineering↗

bioRxiv2023

Electron-bifurcation and fluoride efflux systems in Acetobacterium spp. drive defluorination of perfluorinated unsaturated carboxylic acids

Enzymatic cleavage of C-F bonds in per- and polyfluoroalkyl substances (PFAS) is largely unknown but avidly sought to promote systems biology for PFAS bioremediation. Here, we report the reductive defluorination of , {beta}-unsaturated per- and polyfluorocarboxylic acids by Acetobacterium spp. Two critical molecular features in Acetobacterium species enabling reductive defluorination are (i) a functional fluoride efflux transporter (CrcB) and (ii) an electron-bifurcating caffeate reduction pathway (CarABCDE). The fluoride transporter was required for detoxification of released fluoride. Car enzymes were implicated in defluorination by the following evidence: (i) only Acetobacterium spp. with car genes catalyzed defluorination; (ii) caffeate and PFAS competed in vivo; (iii) models from the X-ray structure of the electron-bifurcating reductase (CarC) positioned the PFAS substrate optimally for reductive defluorination; (iv) products identified by 19F-NMR and high-resolution mass spectrometry were consistent with the model. Defluorination biomarkers identified here were found in wastewater treatment plant metagenomes on six continents.

microbiology↗