Injectable scaffolds are appealing for tissue regeneration because they offer many advantages over pre-formed scaffolds. This article provides a comprehensive review of the injectable scaffolds currently being investigated for dental and craniofacial tissue regeneration. First, we provide an overview of injectable scaffolding materials, including natural, synthetic, and composite biomaterials. Next, we discuss a variety of characteristic parameters and gelation mechanisms of the injectable scaffolds. The advanced injectable scaffolding systems developed in recent years are then illustrated. Furthermore, we summarize the applications of the injectable scaffolds for the regeneration of dental and craniofacial tissues that include pulp, dentin, periodontal ligament, temporomandibular joint, and alveolar bone. Finally, our perspectives on the injectable scaffolds for dental and craniofacial tissue regeneration are offered as signposts for the future advancement of this field.

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Formation of bacterial biofilms on dental implant material surfaces (titanium) may lead to the development of peri-implant diseases influencing the long term success of dental implants. In this study, a novel Cu-bearing titanium alloy (Ti-Cu) was designed and fabricated in order to efficiently kill bacteria and discourage formation of biofilms, and then inhibit bacterial infection and prevent implant failure, in comparison with pure Ti. Results from biofilm based gene expression studies, biofilm growth observation, bacterial viability measurements and morphological examination of bacteria, revealed antimicrobial/antibiofilm activities of Ti-Cu alloy against the oral specific bacterial species, Streptococcus mutans and Porphyromonas gingivalis. Proliferation and adhesion assays with mesenchymal stem cells, and measurement of the mean daily amount of Cu ion release demonstrated Ti-Cu alloy to be biocompatible. In conclusion, Ti-Cu alloy is a promising dental implant material with antimicrobial/antibiofilm activities and acceptable biocompatibility.

The emerging photoluminescent carbon-based nanomaterials are promising in various fields besides cell imaging and carrier transport. Carbon nanomaterials with specific biological functions, however, are rarely investigated. Aspirin is a very common anti-inflammatory medication to relieve aches and pains. In this study, we have tried to create a carbon nanoparticle with aspirin, and we expect that this new carbon nanoparticle will have both anti-inflammatory and fluorescent biomarker functions. Fluorescent aspirin-based carbon dots (FACDs) were synthesized by condensing aspirin and hydrazine through a one-step microwave-assisted method. Imaging data demonstrated that FACDs efficiently entered into human cervical carcinoma and mouse monocyte macrophage cells in vitro with low cell toxicity. Results from quantitative polymerase chain reaction and histological analysis indicated that FACDs possessed effective anti-inflammatory effects in vitro and in vivo compared to aspirin only. Hematology, serum biochemistry, and histology results suggested that FACDs also had no significant toxicity in vivo. Our results clearly demonstrate that FACDs have dual functions, cellular imaging/bioimaging and anti-inflammation, and suggest that FACDs have great potential in future clinical applications.

Understanding cell-material interactions is a prerequisite for the development of bio-inspired materials for tissue regeneration. While nanofibrous biomaterials have been widely used in tissue regeneration, the effects of nanofibrous architecture on stem cell behaviors are largely ambiguous because the previous biomaterial systems used for nanofiber-cell interactions could not exclude the interference of cell-cell interactions. In this study, we developed a unique micropatterning technology to confine one single stem cell in a microisland of the nanofibrous micropatterned matrix; therefore, eliminating any potential intercellular communications. The nanofibrous micropatterned matrix, which mimicked both the physical architecture and chemical composition of natural extracellular matrix, was fabricated by a combination of electrospinning, chemical crosslinking, and UV-initiated photolithography. Compared to the non-nanofibrous architecture, a bone marrow mesenchymal stem cell (BMSC) cultured on the nanofibrous microisland exhibited a more in vivo-like morphology, a smaller spreading area, less focal adhesion, and fewer stress fibers. The BMSC cultured on the nanofibrous microisland also had higher alkaline phosphatase activity, indicating nanofibrous architecture promoted BMSC differentiation. A mechanistic study reveals that nanofibers regulate single BMSC osteogenesis via the FAK/RhoA/YAP1 pathway. The nanofibrous micropatterned matrix developed in this study is an excellent platform to promote the fundamental understanding of cell-matrix interactions, ultimately provide valuable insights for the development of novel bio-inspired scaffolds for tissue regeneration.

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MicroRNAs (miRNAs) are emerging as a novel class of molecular targets and therapeutics to control gene expression for tissue repair and regeneration. However, a safe and effective transfection of miRNAs...

Micropatterning is a widely used powerful tool to create highly ordered microstructures on material surfaces. However, due to technical limitations, the integration of micropatterned microstructures into bioinspired 3D scaffolds to successfully regenerate well-organized functional tissues is not achieved. In this work, a unique maskless micropatterning technology is reported to create 3D nanofibrous matrices with highly organized tubular architecture for tissue regeneration. This micropatterning method is a laser-guided, noncontact, high-precision, flexible computer programming of machining process that can create highly ordered tubules with the density ranged from 1000 to 60 000 mm and the size varied from 300 nm to 30 µm in the bioinspired 3D matrix. The tubular architecture presents pivotal biophysical cues to control dental pulp stem cell alignment, migration, polarization, and differentiation. More importantly, when using this 3D tubular hierarchical matrix as a scaffold, this study successfully regenerates functional tubular dentin that has the same well-organized microstructure as its natural counterpart. This 3D maskless micropattern approach represents a powerful avenue not only for the exploration of cell-material interactions in 3D, but also for the regeneration of functional tissues with well-organized microstructures.