Versatile 3D Printing Scaffold with Spatiotemporal Release of Multiple Drugs for Bone Regeneration
Zelin Zhu, Cairong Li, Yating Lin, Chunlin Li, Kun Liu, Wei Wen, Shan Ding, Changren Zhou, Yuxiao Lai, Binghong Luo
Abstract
Implanting a three-dimensional (3D) printing scaffold is one of the most effective ways for treating bone defects. However, the process of bone repair is extremely complex, which requires the scaffold to comply with this process, play early antibacterial roles after implantation, and promote angiogenesis and osteogenesis in the later stage. In this study, layered double hydroxides (LDHs), a type of 2D inorganic nanomaterial, were employed to efficiently load osteogenic and angiogenic dimethyloxalylglycine (DMOG) based on anion exchange. Further, the DMOG-loaded LDHs and eugenol, a natural antibacterial agent, were simultaneously modified onto the surface of 3D printing poly( L -lactide) (PLLA) scaffolds via a polydopamine layer, thereby constructing a 3D printing scaffold capable of realizing spatiotemporally controlled release of different bioactive drugs. Specifically, eugenol is released rapidly in the early stage to play an antibacterial role, while DMOG is sustainably released from the LDHs to promote long-term osteogenesis and angiogenesis. Besides, the surface-coated DMOG-loaded LDHs can not only mechanically strengthen the 3D printing PLLA scaffold but also promote the osteogenic activity of the scaffold due to the released Mg 2+ with the decomposition of LDHs. Also noteworthy, we found that eugenol, DMOG, and LDHs exert synergistic effects in promoting the proliferation, angiogenesis, and osteogenic differentiation of cells in vitro, as well as accelerating vascularized bone formation in vivo. This work presents an approach to fabricating 3D-printed scaffolds with spatiotemporal release capabilities for multiple drugs, advancing bone repair.