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Herpes simplex virus (HSV) infection is the most common cause of corneal blindness in the Western world.
Despite effective anti-viral drugs such as acyclovir (ACV), disease recurrence due to the virus establishing latency within
the corneal nerves and possibly cells makes treatment very challenging. Furthermore, although effective, current systemic
and topical preparations of anti-viral drugs do not appear to deliver sufficient quantities to the cornea to prevent
reactivation. Current treatment for HSV vision loss is transplantation with donor corneas, but the surgery itself can
reactivate viruses. We examined the feasibility of preventing viral reactivation during surgery, by sustained delivery of
ACV introduced during corneal transplantation surgery, through encapsulation of the drug within silica (SiO2)
nanoparticles (NP) incorporated into biosynthetic alternatives to donor corneas. We show that incorporation of NPs did
not affect optical clarity of the collagen-based corneal substitutes nor their biocompatibility. NP-encapsulation effectively
sustained ACV release from the biosynthetic implants over 10 days, compared to free ACV incorporated directly into the
hydrogel constructs. The NP-enabled sustained release resulted in effective prevention of virally-induced cell death, not
observed with the free drug. This early model demonstrates the feasibility of using biomimetic corneal substitutes that
incorporate a drug release system (e.g. silica nanoparticles encapsulating ACV) as future alternatives to human donor
tissue grafts, for transplantation of HSV-infected corneas.