Engineered Mesenchymal Stromal Cell Exosomes-Loaded Microneedles Improve Corneal Healing after Chemical Injury.

ABSTRACT

Corneal alkali burns represent a prevalent ophthalmic emergency with the potential to induce blindness. The main contributing mechanisms include excessive inflammation and delayed wound healing. Existing clinical therapies have limitations, promoting the exploration of alternative methods that offer improved efficacy and reduced side effects. Adipose-derived stem cell-exosome (ADSC-Exo) has the potential to sustain immune homeostasis and facilitate tissue regeneration. Nevertheless, natural ADSC-Exo lacks disease specificity and exhibits limited bioavailability on the ocular surface. In this study, we conjugated antitumor necrosis factor-α antibodies (aT) to the surface of ADSC-Exo using matrix metalloproteinase-cleavable peptide chains to create engineered aT-Exo with synergistic effects. In both in vivo and in vitro assessments, aT-Exo demonstrated superior efficacy in mitigating corneal injuries compared to aT alone, unmodified exosomes, or aT simply mixed with exosomes. The cleavable conjugation of aT-Exo notably enhanced wound healing and alleviated inflammation more effectively. Simultaneously, we developed poly(vinyl alcohol) microneedles (MNs) for precise and sustained exosome delivery. The in vivo results showcased the superior therapeutic efficiency of MNs compared with conventional topical administration and subconjunctival injection. Therefore, the bioactive nanodrugs-loaded MNs treatment presents a promising strategy for addressing ocular surface diseases.