Three-dimensional (3D) printing technology has great potential in advancing clinical medicine. Currently, the in vivo application strategies for 3D-printed macroscale products are limited to surgical implantation or in situ 3D printing at the exposed trauma, both requiring exposure of the application site. Here, we show a digital near-infrared (NIR) photopolymerization (DNP)–based 3D printing technology that enables the noninvasive in vivo 3D bioprinting of tissue constructs. In this technology, the NIR is modulated into customized pattern by a digital micromirror device, and dynamically projected for spatially inducing the polymerization of monomer solutions. By ex vivo irradiation with the patterned NIR, the subcutaneously injected bioink can be noninvasively printed into customized tissue constructs in situ. Without surgery implantation, a personalized ear-like tissue constructs with chondrification and a muscle tissue repairable cell-laden conformal scaffold were obtained in vivo. This work provides a proof of concept of noninvasive in vivo 3D bioprinting.

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.

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.

Cancer cell proliferation in some organs often depends on conversion of pyruvate to oxaloacetate via pyruvate carboxylase (PC) for replenishing the tricarboxylic acid cycle to support biomass production. In this study, PC was identified as the cellular target of erianin using the photoaffinity labeling-click chemistry-based probe strategy. Erianin potently inhibited the enzymatic activity of PC, which mediated the anticancer effect of erianin in human hepatocellular carcinoma (HCC). Erianin modulated cancer-related gene expression and induced changes in metabolic intermediates. Moreover, erianin promotes mitochondrial oxidative stress and inhibits glycolysis, leading to insufficient energy required for cell proliferation. Analysis of 14 natural analogs of erianin showed that some compounds exhibited potent inhibitory effects on PC. These results suggest that PC is a cellular target of erianin and reveal the unrecognized function of PC in HCC tumorigenesis; erianin along with its analogs warrants further development as a novel therapeutic strategy for the treatment of HCC.

Multiple thioether-inserted lipophilic prodrugs co-assembled into FRET nanoaggregates for light-activated drug release by structure destruction.