Engineered biodegradables fibres for brain metal ion regulation.

Exposure to environmental heavy metals and disruptions in physiological metal homeostasis are significant contributors to neurological and neurodegenerative disorders. To counteract heavy metal toxicity, a biopolymer consisting of chitosan functionalized with DOTAGA ligands (Chitosan@DOTAGA) was developed. By blending conventional chitosan with Chitosan@DOTAGA, biodegradable fibres with controlled diameters (192.3 ± 14.5 μm) were engineered and their mechanical properties characterized (Young's modulus of 0.115 ± 0.014 cN/dtex, yield stress of 0.288 ± 0.013 cN/dtex, tenacity of 0.47 ± 0.02 cN/dtex…). The chelation capacity of these fibres was assessed in an aqueous medium via ICP-MS analysis for various metal ions, including Cu(II), Cd(II), Pb(II), and Fe(III). Neuroprotective effects were evaluated ex vivo using nerve terminals isolated from rat brains exposed to Cu(II), Cd(II), Pb(II), and Hg(II); effectiveness was evidenced for all metals except Hg (II) testing transportation of excitatory and inhibitory neurotransmitters, L-[14C] glutamate (and [3H] GABA, and varied between 30 and 80 % within the line Cd(II)-Pb(II)-Cu(II). To validate the in vivo feasibility of the future use of Chitosan@DOTAGA for metal chelation in the central nervous system, Gd(III)-labeled fibres were implanted into rat brains for three months, with no observable inflammatory reactions detected via MRI or histology. Fibre biodegradability was assessed using MRI and ICP-MS analyses showing around 40 % of degradation after 17 weeks of implantation. SIGNIFICANCE: The ability to effectively remove excess metals from the brain is critical for treating various neurological disorders where metal accumulation contributes to disease pathology. Traditional chelation therapies face significant challenges, particularly in crossing the blood-brain barrier and selectively targeting affected areas. In this study, we introduce a biodegradable chelating polymer designed for implantation during surgical procedures. Our findings highlight neuroprotective properties ex vivo and promising safety in vivo in rodent model.