Lin Chen, Bai Xinyi, Zhang Linkun
Department of Orthodontics, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, 300041, People's Republic of China.
Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, 300041, China.
Int J Nanomedicine. 2024 Dec 2;19:12939-12956. doi: 10.2147/IJN.S481965. eCollection 2024.
MicroRNA-34c-5p (miR-34c-5p) plays a pivotal role in bone remodeling, yet its therapeutic potential is hindered by challenges such as instability, limited cellular internalization, and immune responses. This study was aimed at developing innovative scaffolds capable of efficiently delivering microRNAs (miRNAs), specifically miR-34c-5p.
Chitosan (CS)/sodium tripolyphosphate (STPP)/sodium alginate (SA) scaffolds, referred to as CTS scaffolds, were synthesized at a specific ratio and characterized using dynamic light scattering and scanning electron microscopy (SEM). Cytotoxicity assessments were conducted through cell activity staining. The loading capacity and releasing performance of miRNAs were quantified using spectrophotometry. Subsequently, the in vivo efficacy of miR-34c-5p Agomir/Antagomir in regulating bone repair was evaluated in the rabbit cranial bone defect model, with micro-CT scanning and histological analysis conducted at 4, 8, and 12 weeks.
CTS scaffolds with a composition ratio of 1:0.2:0.1 were successfully synthesized, exhibiting a mean particle size of 360.1 nm. SEM revealed scaffolds had the porous spongy structure. Cell activity staining confirmed the excellent biocompatibility of the CTS scaffolds. Spectrophotometry demonstrated miR-34c-5p Antagomir were continually released, reaching 91.41% within 30 days. Differential new bone formation was observed between the miR-34c-5p Agomir and Antagomir groups. Micro-CT imaging and histological staining revealed varying degrees of bone regeneration, with notable improvements in the miR-34c-5p Antagomir group.
CTS scaffolds with a composition ratio of 1:0.2:0.1 demonstrate favorable biocompatibility and enable efficient loading and sustained release of miR-34c-5p Antagomir. The study suggests potential applications of miR-34c-5p Antagomir in promoting bone repair and highlights the promise of innovative scaffolds for therapeutic miRNAs administration in bone regeneration.
微小RNA-34c-5p（miR-34c-5p）在骨重塑中起关键作用，但其治疗潜力受到诸如不稳定性、有限的细胞内化和免疫反应等挑战的阻碍。本研究旨在开发能够有效递送微小RNA（miRNA），特别是miR-34c-5p的创新支架。
以特定比例合成壳聚糖（CS）/三聚磷酸钠（STPP）/海藻酸钠（SA）支架，称为CTS支架，并使用动态光散射和扫描电子显微镜（SEM）对其进行表征。通过细胞活性染色进行细胞毒性评估。使用分光光度法定量miRNA的负载能力和释放性能。随后，在兔颅骨缺损模型中评估miR-34c-5p激动剂/拮抗剂在调节骨修复中的体内疗效，在4、8和12周时进行显微CT扫描和组织学分析。
成功合成了组成比例为1:0.2:0.1的CTS支架，平均粒径为360.1nm。SEM显示支架具有多孔海绵结构。细胞活性染色证实了CTS支架具有优异的生物相容性。分光光度法表明miR-34c-5p拮抗剂持续释放，30天内达到91.41%。在miR-34c-5p激动剂组和拮抗剂组之间观察到不同的新骨形成。显微CT成像和组织学染色显示出不同程度的骨再生，miR-34c-5p拮抗剂组有显著改善。
组成比例为1:0.2:0.1的CTS支架表现出良好的生物相容性，能够有效负载和持续释放miR-34c-5p拮抗剂。该研究表明miR-34c-5p拮抗剂在促进骨修复方面的潜在应用，并突出了创新支架在骨再生中用于治疗性miRNA给药的前景。
