No abstract

End-to-end neurorrhaphy is the most commonly used method for treating peripheral nerve injury. However, only 50% of patients can regain useful function after treating with neurorrhaphy. Here, we constructed a 3D-engineered porous conduit to promote the function recovery of the transected peripheral nerve after neurorrhaphy. The conduit that consisted of a gelatin cryogel was prepared by molding with 3D-printed moulds. Due to its porous structure and excellent mechanical properties, this conduit could be collapsed by the mechanical force and resumed its original shape after absorption of normal saline. This shape-memory property allowed a simply surgery process for installing the conduits. Moreover, the biodegradable conduit could prevent the infiltration of fibroblasts and reduce the risk of scar tissue, which could provide an advantageous environment for nerve regeneration. The efficiency of the conduits in assisting peripheral nerve regeneration after neurorrhaphy was evaluated in a rat sciatic nerve transected model. Results indicated that conduits significantly benefitted the recovery of the transected peripheral nerve after end-to-end neurorrhaphy on the static sciatic index (SSI), electrophysiological results and the re-innervation of the gastrocnemius muscle. This work demonstrates a biodegradable nerve conduit that has potentially clinical application in promoting the neurorrhaphy.

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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.

Platelets can secrete multiple growth factors for peripheral nerve repair. However, topically injected platelets are rapidly activated followed by burst release of the cargos, causing limited therapeutic efficiency in vivo. Herein, a platelet-incorporated hydrogel conduit is shown that acts as a biosynthetic nerve conduit for peripheral nerve repair. This conduit is prepared by rapid 3D printing of the live platelets mixed with bio-ink containing gelatin methacrylate (GelMA) and poly(ethyleneglycol)diacrylate (PEGDA). The hydrogel can significantly prolong the survival of the incorporated platelets. While the conduit provides a physical foundation for bridging the nerve gaps, live platelets in the conduit sustained-release multiple growth factors to promote the nerve repair. The in vivo therapeutic efficiency of this platelet-incorporated nerve conduit is tested in bridging a 10 mm gap in sciatic nerves. The results of morphological, electrophysiological, and histological assessments indicate that the incorporated platelets can significantly promote the hydrogel conduits in peripheral nerve repair. The demonstrated 3D bioprinted nerve conduit with live platelets may show potential clinical application in peripheral nerve repair.