Therapeutic agents such as mRNA fragments are delivered to a patient to treat
peripheral nerve
system injuries via functionalized
fiber networks. The
fiber networks are electrospun from poly(L-
lactic acid), producing a hollow conduit of aligned fibers. The networks are functionalized with an anionic layer, e.g.,
dextran sulfate sodium salt (DSS), poly(3,4-dihydroxy-L-
phenylalanine) (pDOPA). mRNA complexes including a cationic liposomal
transfection portion and an mRNA portion, such as Ψ-modified mRNA encoding
neurotrophin-3 (NT-3), are immobilized thereon. The
fiber networks are positioned to bridge a
peripheral nerve gap in the patient. These networks upregulate
secretion of expressed oligopeptides, e.g., NT-3, by surrounding cells, and thus enhance
neurite outgrowth. The networks serve as versatile non-viral mRNA delivery platforms. The mRNA transcript,
gene delivery vehicle, and surface coatings can be modified to regulate different desired proteins, optimize
transfection efficiency, enable targeted delivery, and tune loading efficiency and release
kinetics.