Pastable, Adhesive, Injectable, Nanofibrous, and Tunable (PAINT) Biphasic Hybrid Matrices as Versatile Therapeutic Carriers

A critical
challenge in many pharmaceutical fields is developing
versatile adjuvant devices that can reduce the off-target delivery
of therapeutic materials to target lesions. Herein, a biphasic hybrid
fibrous system that can manipulate the spatial and temporal delivery
of various therapeutic agents to target lesions by integrating multiple
distinct systems and technologies such as fluffy coaxial electrospun
polycaprolactone (PCL)/polystyrene (PS) fibers, cyclohexane-mediated
leaching to remove PS layers selectively, amine display on PCL fibers,
conjugation of naturally occurring adhesive gallol molecules onto
hyaluronic acid (HA-g), and electrostatically complexing the aminated
PCL fibers with the gallol-conjugated HA. In the context of “paintable”
systems on target lesions, the resulting system is called a PAINT
matrix (abbreviated according to the initial letter of its features:
pastable, adhesive, injectable, nanofibrous, and tunable). Its viscoelastic
property, which was attributed by coalescing aminated PCL fibers with
viscous HA-g, enabled it to be noninvasively injected and fit into
any cavity in the body with various morphologies, manually pasted
on tissue surfaces, and adhered onto moisture-rich surfaces to ensure
the secure delivery of therapeutics toward the target lesions. The
PAINT matrix efficiently supplied immunomodulatory human neural stem
cells (hNSCs) at rat hemisectioned spinal cord injury (SCI) sites
and promoted both locomotive and sensory recovery in SCI models, presumably
by protecting hNSCs against host immunosurveillance. The PAINT matrix
will be broadly utilized for efficiently delivering therapeutics to
difficult-to-reach target lesions by direct infusion or conventional
biomaterial-mediated approaches due to their locations, wet surfaces,
or complicated ambient environments.