A double-crosslinked nanocellulose-reinforced dexamethasone-loaded collagen hydrogel for corneal application and sustained anti-inflammatory activity

• DOI: 10.1016/j.actbio.2023.10.020
• Publication Date: 2023-10-20T15:47:31Z
• Authors: Maria Xeroudaki; Mehrdad Rafat; Petros Moustardas; Anthony Mukwaya; Shideh Tabe; Marco Bellisario; Beatrice Peebo; Neil Lagali
• Keywords: Biocompatibility; Corneal inflammation

In cases of blinding disease or trauma, hydrogels have been proposed as scaffolds for corneal regeneration and vehicles ocular drug delivery. Restoration transparency, augmenting a thin cornea postoperative delivery are particularly challenging in resource-limited regions where availability patient compliance may be suboptimal. Here, we report bioengineered hydrogel based on porcine skin collagen an alternative to human donor tissue applications long-term stability the is required. The reinforced with cellulose nanofibers extracted from Ciona intestinalis sea invertebrate followed by double chemical photochemical crosslinking. additionally loaded dexamethasone provide sustained anti-inflammatory activity. double-crosslinked after loading maintained high optical transparency significantly improved mechanical characteristics compared non-reinforced hydrogels, while supporting gradual release 60 days vitro. Dexamethasone, exposure crosslinking sterilization procedures used production, inhibited tube formation cell migration TNFα-stimulated vascular endothelial cells. drug-loaded suppressed key pro-inflammatory cytokines CCL2 CXCL5 epithelial Eight weeks intra-stromal implantation 12 New-Zealand white rabbits subjected inflammatory suture stimulus, dexamethasone-releasing TNFα, MMP-9, leukocyte fibroblast invasion, resulting reduced haze, thickness stromal morphology, overall vessel invasion. This collagen-nanocellulose can implanted treat suppressing inflammation maintaining transplantation. STATEMENT OF SIGNIFICANCE: To diseases, facilitate restoration improve clinically tested collagen-based scaffold robustness enzymatic resistance incorporating sustainably sourced nanocellulose dual chemical-photochemical reinforce scaffold, simultaneously achieving incorporated drug, dexamethasone. Evaluated context model inflammation, drug-releasing nanocellulose-reinforced cornea's resisted degradation postoperatively. biomaterial could therefore potentially applied wider range sight-threatening overcoming suboptimal administration medications maintain integrity good vision.