Lihua Li

Treatment of large bone defects derived from bone tumor surgery is typically performed in multiple separate operations, such as hyperthermia to extinguish residual malignant cells or implanting bioactive materials to initiate apatite remineralization for tissue repair; it is very challenging to combine these functions into a material. Herein, we report the first photothermal (PT) effect in bismuth (Bi)-doped glasses. On the basis of this discovery, we have developed a new type of Bi-doped bioactive glass that integrates both functions, thus reducing the number of treatment cycles. We demonstrate that Bi-doped bioglasses (BGs) provide high PT efficiency, potentially facilitating photoinduced hyperthermia and bioactivity to allow bone tissue remineralization. The PT effect of Bi-doped BGs can be effectively controlled by managing radiative and non-radiative processes of the active Bi species by quenching photoluminescence (PL) or depolymerizing glass networks. In vitro studies demonstrate that such glasses are biocompatible to tumor and normal cells and that they can promote osteogenic cell proliferation, differentiation, and mineralization. Upon illumination with near-infrared (NIR) light, the bioglass (BG) can efficiently kill bone tumor cells, as demonstrated via in vitro and in vivo experiments. This indicates excellent potential for the integration of multiple functions within the new materials, which will aid in the development and application of novel biomaterials.

Antibacterial metal ions, such as Ag(+), Zn(2+) and Cu(2+), have been extensively used in medical implants and devices due to their strong broad spectrum of antibacterial activity. However, it is still a controversial issue as to whether they can show the desired antibacterial activity while being toxic to mammalian cells. It is very important to balance their antibacterial effectiveness with minimal damage to mammalian cells. Toward this end, this study is to identify the suitable concentrations of these three ions at which they can effectively kill two types of clinically relevant bacteria (Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)) but show no obvious cytotoxicity on fibroblasts. Such concentration ranges are found to be 2.5 × 10(-7) M-10(-6) M, 10(-5) M-10(-4) M, and 10(-5) M-10(-4) M for Ag(+), Zn(2+), and Cu(2+), respectively. Investigation of their antibacterial mechanism shows that these three metal ions all show antibacterial property through a mechanism of damaging bacterial cell membranes by the generation of reactive oxygen species but surprisingly preserving the integrity of bacterial genomic DNA. The encouraging results indicate that antibacterial metal ions with controlled concentrations can bring considerable benefits to biomedical applications.

Oral infectious diseases and tooth staining, the main challenges of dental healthcare, are inextricably linked to microbial colonization and the formation of pathogenic biofilms. However, dentistry has so far still lacked simple, safe, and universal prophylactic options and therapy. Here, we report copper-doped carbon dots (Cu-CDs) that display enhanced catalytic (catalase-like, peroxidase-like) activity in the oral environment for inhibiting initial bacteria (Streptococcus mutans) adhesion and for subsequent biofilm eradication without impacting the surrounding oral tissues via oxygen (O2) and reactive oxygen species (ROS) generation. Especially, Cu-CDs exhibit strong affinity for lipopolysaccharides (LPS) and peptidoglycans (PGN), thus conferring them with excellent antibacterial ability against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), such that they can prevent wound purulent infection and promoting rapid wound healing. Additionally, the Cu-CDs/H2O2 system shows a better performance in tooth whitening, compared with results obtained with other alternatives, e.g., CDs and clinically used H2O2, particularly its negligible enamel and dentin destruction. It is anticipated that the biocompatible Cu-CDs presented in this work are a promising nano-mouthwash for eliminating oral pathogenic biofilms, prompting wound healing as well as tooth whitening, highlighting their significance in oral health management.

Repairing infected bone defects relies on a scaffold that can not only fill the defects to promote bone formation but also kill clinically present bacterial pathogens such as Staphylococcus aureus (S. aureus). To meet this demand, here, we develop a new copper (Cu) containing natural polymeric scaffold with a full potential for repairing infected bone defects. Instead of directly adding antibacterial Cu2+ ions to the polymer mixtures, which caused uncontrolled polymer cross-linking, we added Cu nanoparticles to the mixture of anionic carboxymethyl chitosan (CMC) and alginate (Alg). Then, the Cu2+ ions released from the Cu nanoparticles gradually cross-linked the polymer mixtures, which was further turned into a scaffold (CMC/Alg/Cu) with an interconnected porous structure by freeze-drying. We found that the CMC/Alg/Cu scaffolds showed significantly improved capabilities of osteogenesis and killing clinical bacteria compared to CMC/Alg scaffolds fabricated by the same procedure but without adding Cu nanoparticles. Specifically, in vitro studies showed that the CMC/Alg/Cu scaffolds with excellent biocompatibility could enhance preosteoblastic cell adhesion by upregulating the expression level of adhesion-related genes (focal adhesion kinase (FAK), paxillin (PXN), and vinculin (VCL)), promoting osteogenic differentiation and mineralization by upregulating the osteogenesis-related gene expression and extracellular calcium deposition. In vivo studies further demonstrated that CMC/Alg/Cu scaffolds could induce the formation of vascularized new bone tissue in 4 weeks while avoiding clinical bacterial infection even when the implantation sites were challenged with the clinically collected S. aureus bacteria. This work represents a facile and innovative approach to the fabrication of Cu containing polymer scaffolds that can potentially be used to repair infected bone defects.