Oral soft tissue engineering involves the reconstruction or restoration of oral and maxillofacial functions and esthetics. As an emerging technology from the early 21st century, three-dimensional (3D) bioprinting promises great application potentials in the preparation of scaffolds and engineered tissues/organs. Although oral soft tissues include dental pulp, periodontal ligament, gum, oral mucosa, and salivary glands as well as related maxillofacial skin, vascular, muscular, and neuronal tissues, the current application of 3D bioprinting in oral soft tissue-restoration is mainly limited to dental pulp-regeneration. Different bioinks are used to load dental pulp cells into the dentin matrix for restoring the dental pulp tissue; 3D bioprinting has only been reported in a few in vitro studies on periodontal ligament-reconstruction and salivary gland culture; and 3D bioprinting used towards regenerating gingival tissue/oral mucosa has not been demonstrated. The limited application of 3D bioprinting in oral soft tissue engineering is perhaps related to the complex, fine, and orderly structure of the periodontal ligament, the moist environment of the oral cavity, the small operating space, and the continuous chewing pressure. The studies on bioprinting of skin, vascular, muscular, and neuronal tissues are broad, but they are typically not oral-specific. This article introduces the current application status and prospects of 3D bioprinting in the regeneration of oral soft tissues, using cytocompatible hydrogels as bioinks.

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.