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

Yafei Han; Yan Wu; Fuxiao Wang; Guangfeng Li; Jian Wang; Xiang Wu; Anfu Deng; Xiaoxiang Ren; Xiuhui Wang; Jie Gao; Zhongmin Shi; Long Bai; Jiacan Su

doi:10.1016/j.bioactmat.2024.01.009

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

Bioact Mater. 2024 Jan 18:35:1-16. doi: 10.1016/j.bioactmat.2024.01.009. eCollection 2024 May.

Authors

Yafei Han^{1

2

3

4}, Yan Wu^{1

2}, Fuxiao Wang^{1

2

3

4}, Guangfeng Li^{1

2

3

5}, Jian Wang^{1

2

3

4}, Xiang Wu^{1

2

3}, Anfu Deng^{1

2

3}, Xiaoxiang Ren^{1

2}, Xiuhui Wang^{1

2}, Jie Gao³, Zhongmin Shi⁶, Long Bai^{1

2

7}, Jiacan Su^{1

8

2}

Affiliations

¹ Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
² National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China.
³ School of Medicine, Shanghai University, Shanghai, 200444, China.
⁴ School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China.
⁵ Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200444, China.
⁶ National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, 200233, China.
⁷ Wenzhou Institute of Shanghai University, Wenzhou, 325000, China.
⁸ Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

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.

Keywords: Angiogenesis; Aptamer02; Bone regeneration; DNA hydrogel; tFNA.