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

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Heterogeneous DNA hydrogel loaded with Apt02 modified tetrahedral framework nucleic acid accelerated critical-size bone defect repair
Bioactive Materials ( IF 18.0 ) Pub Date : 2024-01-18 , DOI: 10.1016/j.bioactmat.2024.01.009
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 Gao ₃ , Zhongmin Shi ₆ , Long Bai _{1,

2,

7} , Jiacan Su _{1,

2,

8}

Affiliation

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. 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.

中文翻译：

载样 Apt02 修饰四面体骨架核酸的异质 DNA 水凝胶加速临界大小骨缺损修复

由创伤、感染和肿瘤引起的节段性骨缺损构成了艰巨的临床挑战。传统的骨修复材料，如自体和同种异体骨移植物，面临着包括来源稀缺和免疫排斥风险在内的局限性。核酸纳米技术的出现，特别是 DNA 水凝胶在组织工程中的应用，由于其生物相容性、生物降解性和可编程性，提出了一个有前途的解决方案。然而，这些水凝胶通常受到高凝胶温度（∼46 °C）和高构建成本的阻碍，限制了细胞封装和更广泛的应用。我们的研究引入了一种新型聚合物修饰的 DNA 水凝胶，该水凝胶采用核酸纳米技术开发，可在 37 °C 的生物相容性更强的温度下凝胶化，并且具有成本效益。然后，该水凝胶掺入四面体框架核酸（tFNA）以增强成骨矿化。此外，考虑到 tFNA 的可修饰性，我们用 Aptamer02 （Apt02）修饰了它的链，Aptamer02 （Apt02）是一种已知促进血管生成的适配体。这种双重方法显着加速了骨髓基质细胞（BMSC）的成骨分化和人脐静脉内皮细胞（HUVEC）的血管生成，细胞测序分别证实了它们的靶向功效。在具有临界大小颅骨缺损的大鼠中进行的实验证明了它们在增强新骨形成方面的有效性。这项创新不仅为修复节段性骨缺损提供了可行的解决方案，还为骨类器官构建的未来发展开辟了道路，标志着组织工程和再生医学的重大进步。

更新日期：2024-01-18

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