Caballero-Aguilar, L. M. | Search bioRxiv

bioRxiv2026

Selonsertib-Eluting Electrode Coating Attenuates Cochlear Injury Pathways

Cochlear implants partially restore sound sensation for individuals with severe-to-profound hearing loss. This can significantly improve the recipients quality of life, largely through improved communication with spoken language. However, surgical trauma from electrode insertion also instigates biological responses that can compromise device performance and longevity. To address these limitations, we designed a novel polymer-based coating that provides controlled release of selonsertib, an apoptosis signal-regulating kinase 1 (ASK1) inhibitor with well described anti-inflammatory, anti-fibrosis and cytoprotective properties. We describe the physical and molecular evaluation of this coating, including the application of next generation mass spectrometry-based proteomics in mammalian cochlear explants and their culture medium. These analyses provide new insights into the acute tissue response in the damaged cochlea and demonstrate that selonsertib eluted from the polymer coating has a significant pro-survival, anti-inflammatory, and anti-fibrosis effect. This study establishes proof-of-concept for selonsertib-eluting polymers, demonstrating both feasibility for targeted drug delivery and efficacy for mitigating acute cochlear damage responses.

neuroscience↗

bioRxiv2022

Incorporation of bioactive peptides into peptide nanofibrillar hydrogels affects their nanostructure, mechanical properties and biocompatibility

Self-assembling peptides are promising candidates as scaffolds for 3D cell cultures. These hydrogels offer favourable biocompatibility, nanofibrillar structures that mimic native tissues, and the convenient integration of bioactive peptide sequences, such as arginine-glycine-aspartic acid (RGD), which can enable the development of therapeutically valuable cell types. In the treatment of osteoarthritis (OA) attempts have been made to combine hydrogel scaffolds with mesenchymal stem cells (MSCs) to harness their regenerative potential. This involves the deposition of extracellular matrix (ECM) components like collagen and proteoglycans. Here, we employ the hydrogel-forming peptide Fmoc-diphenylalanine (Fmoc-FF) and incorporate stoichiometric amounts of Fmoc-RGD. We investigate the impact of RGD on nanofibrillar morphologies, hydrogel stability, MSC viability, and the deposition of collagen, proteoglycans, and glycosaminoglycans. Elevating RGD content enhances cell viability and collagen deposition. However, at higher RGD concentrations, the stability of the hydrogels is compromised. To characterise collagen deposition, we introduce a non-destructive and label-free method using a plasmon-enhanced colorimetric histology technique. This innovation provides a practical means to image collagen without resorting to intricate and destructive sample processing and complex immunohistological staining procedures. This simple approach holds broad potential for routine and label-free quantification of collagen-rich biomaterials, promising widespread applications across various research and clinical settings.

bioengineering↗