Biomedical applications of copper-impregnated bioactive glass

Bioactive glass (BG) is generally reckoned as an active constituent that both bonds with skeleton and connects with cartilage. This active material often releases the active ions in a controlled fashion via degradation, which is of particular interest in clinical medicine. However. monodispersed bioactive glass without modification still exists limitations, e.g., aggregation or lower activities both in vitro and in vivo. Owing to its unique morphology, distinctive cell uptake process, excellent degradation and biomineralization ability. as well as certain high biosafety, functionalized bioactive glass plays a key role in diverse biomedical applications such as bioimaging, gene/drug delivery and wound healing, facilitating the self-repair and regeneration of tissues. The interesting physicochemical properties of bioactive glass can be adjusted by appropriately selecting active ions, especially metal ions, as impregnated components to alter original bridging oxygen (BO) network to non-bridging oxygen (NBO) structure. In terms of the difference in matrix, bioactive glass is generally devided into three types, i.e., silicate, borate. and phosphate-based architectures. As a universal element in human physiological fluids, copper ions can also be impregnated in the structure of bioactive glass. in which these species not only affect the signal pathway and metabolic activity, but also serve as essential cofactors for many enzymes. After the ion exchange with the surrounding fluidic environment copper ions can be precisely released at the desired site, minimizing the adverse effects. On the one hand, the impregnated copper ions inhibit the activity of osteoclast and stimulate the generation and aggregation of collagens. which significantly impact on the formation and healing of skeleton and cartilage. On the other hand, these copper species not only upregulate the expresssion of fibroblast growth factor (FGF)-2 and hypoxia inducible factor (HIF)-1 alpha, but also enhance the production of endothelial nitric oxide synthase, subsequently promoting the proliferation and migration of human endothelial cells. In addition, the doped copper species are capable of bonding with mercapto, imidazole, carboxyl and amine. among others. to make changes in the membrane structure, including permeability augmentation and membrane transport dysfunction, indicating efficient antibacterial ability. Besides, hyperthermia process appears due to the photothermal effect after the irridation of near-infrared. In another case, copper ions participate in Fenton-like reaction under the acidic microenvironment of tumors, converting glutathione to oxidized glutathione, catalyzing the generation of reactive oxygen species (ROS), thus leading to the damage of mitochondria, ultimately inducing the apoptosis of cancer cells. Currently, it is required to achieve clinical translation from laboratory' outcomes. Despite of a series of advantegeous features, the biomedical applications of copper-impregnated bioactive glass are still facing great challenges. To further facilitate the superiority of this prospective field, the developmental proposals are systemically discussed in this review. Further, critical discussions on effectively solving the aggregation caused by high-temperature sintering process and the denaturation induced by organic solvent utilization are emphasized. Moreover, the encapsulation mechanisms of certain molecules and compensate for the dificient exertion in cancer therapeutics are elaborated, providing an innovative and uninvasive platform in the field of prosperous biomedicine.