A 3D-Printed Self-Adhesive Bandage with Drug Release for Peripheral Nerve Repair

Abstract

Peripheral nerve injury is a common disease that often causes disability and challenges surgeons. Drug-releasable biomaterials provide a reliable tool to regulate the nerve healing-associated microenvironment for nerve repair. Here, a self-adhesive bandage is designed that can form a wrap surrounding the injured nerve to promote nerve regeneration and recovery. Via a 3D printing technique, the bandage is prepared with a special structure and made up of two different hydrogel layers that can adhere to each other by a click reaction. The nanodrug is encapsulated in one layer with a grating structure. Wrapping the injured nerve, the grating layer of the bandage is closed to the injured site. The drug can be mainly released to the inner area of the wrap to promote the nerve repair by improving the proliferation and migration of Schwann cells. In this study, the bandage is used to assist the neurorrhaphy for the treatment of complete sciatic nerve transection without obvious defect in rats. Results indicate that the self-adhesive capacity can simplify the installation process and the drug-loaded bandage can promote the repairing of injured nerves. The demonstrated 3D-printed self-adhesive bandage has potential application in assisting the neurorrhaphy for nerve repair.

Keywords: 3D printing; biomaterials; drug delivery; peripheral nerve repair; self‐adhesive bandages.

Figure 1

The 3D printed self‐adhesive drug‐loaded bandage surrounding a nerve and releasing drugs. A) Scheme for fabricating the self‐adhesive drug‐loaded bandage, a rectangle layer is printed by DBCO‐GelMA, then a grating layer is printed by N₃‐GelMA combined with XMU‐MP‐1 nanoparticles. B) Scheme of the microenvironment that injured nerves are in, the bandage adhere itself by the click reaction of −N₃ and –DBCO, the drugs loaded in the grating layer are directionally released to inner side of the wrap.

Figure 2

Structure and biocompatibility characterization of the self‐adhesive bandages. A) 3D printed self‐adhesive bandage before rolling, camera photo (bar = 5 mm); fluorescence images of the top view and side view of the bandage, red (rhodamine) and green (FITC) showed the rectangle layer and the grating layer in turn (bar = 500 µm). B) The bandage after rolling and self‐adhering, camera photo (bar = 5 mm); SEM images showed the self‐adhered part (bar = 200 µm). C) S16 viabilities in DMEM extract of the bandage (100%, 50%, 25%, 12.5%, 6.25%, 0). These data are presented as mean ± standard deviation, n = 3, one‐way ANOVA, NS. D) Degradation rate of self‐adhesive bandage in collagenase I (0.5 mg mL⁻¹). These data are presented as mean ± standard deviation, n = 3. E) Degradation degree of self‐adhesive bandage in the back of the SD rats, hydrogels almost disappeared after 15 weeks.

Figure 3

Preparation of XMU‐MP‐1 loaded nanoparticles and in vitro demonstration of drug release. A) MPEG‐PCL formed a core–shell structure: a hydrophobic PCL core and a hydrophilic PEG shell, the nanoparticles encapsulated drugs in the core by self‐assembling. B) Scheme of drug release model simulated the release in vivo, green is the outside hydrogel and red is the inside hydrogel containing nanoparticles, both of them are in a container (gray). C) The collected curcumin solution in the inside and outside of the model respectively from the first day to the seventh day. D) The accumulated quantities of XMU‐MP‐1 released to inside and outside from the first day to the seventh day, the quantity of the inner XMU‐MP‐1 was significantly higher than that of the outer XMU‐MP‐1. These data are presented as mean ± standard deviation, n = 3, Student's t‐test, ****p < 0.0001. E) The wound‐healing assay of S16 treated by 0.5 µg mL⁻¹ XMU‐MP‐1 (bar = 200 µm). F) Representative immunofluorescence images showed the distributions of YAP in S16 after treated by 0.5 µg mL⁻¹ XMU‐MP‐1 (bar = 200 µm).

Figure 4

Functional evaluation of the biodegradable self‐adhesive bandages in vivo. A) Conventional observation of the operated nerves and regenerated nerves. B) The NCV value of the regenerated nerves. C) The latency of CMAP onset of the regenerated nerves. These data are presented as mean ± standard deviation, n = 6, one‐way ANOVA, **p < 0.01, ***p < 0.001.

Figure 5

Histological analysis of repaired nerves and surrounding muscles. A) H&E of repaired nerves (bar = 100 µm). B,C) Axon and myelin sheath in light microscope (bar = 50 µm) and TEM (bar = 50 µm). D) Diameter of myelin sheath. These data are presented as mean ± SEM, n = 16, one‐way ANOVA, *p < 0.05, **p < 0.01, ****p < 0.0001. E) H&E of muscles (bar = 50 µm). F) Diameter of muscle fibers. These data are presented as mean ± SEM, n = 90, one‐way ANOVA, ***p < 0.001.