Heterogeneous DNA hydrogel loaded with Apt02 modified tetrahedral framework nucleic acid accelerated critical-size bone defect repair

Abstract

Segmental bone defects, stemming from trauma, infection, and tumors, pose formidable clinical challenges. Traditional bone repair materials, such as autologous and allogeneic bone grafts, grapple with limitations including source scarcity and immune rejection risks. The advent of nucleic acid nanotechnology, particularly the use of DNA hydrogels in tissue engineering, presents a promising solution, attributed to their biocompatibility, biodegradability, and programmability. However, these hydrogels, typically hindered by high gelation temperatures (∼46 °C) and high construction costs, limit cell encapsulation and broader application. Our research introduces a novel polymer-modified DNA hydrogel, developed using nucleic acid nanotechnology, which gels at a more biocompatible temperature of 37 °C and is cost-effective. This hydrogel then incorporates tetrahedral Framework Nucleic Acid (tFNA) to enhance osteogenic mineralization. Furthermore, considering the modifiability of tFNA, we modified its chains with Aptamer02 (Apt02), an aptamer known to foster angiogenesis. This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs), with cell sequencing confirming their targeting efficacy, respectively. In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation. This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction, marking a significant advancement in tissue engineering and regenerative medicine.