Liao Wei, Lu Jingwei, Wang Qianjin, Yan Sen, Li Yan, Zhang Yibo, Wang Peng, Jiang Qing, Gu Ning
Children's Hospital of Nanjing Medical University, Nanjing, China.
School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.
Front Bioeng Biotechnol. 2022 Apr 29;10:872149. doi: 10.3389/fbioe.2022.872149. eCollection 2022.
Smart biomaterials combined with stem cell-based therapeutic strategies have brought innovation in the field of bone tissue regeneration. However, little is known about precartilaginous stem cells (PCSCs), which can be used as seed cells and incorporated with bioactive scaffolds for reconstructive tissue therapy of bone defects. Herein, iron oxide nanoparticles (IONPs) were employed to modulate the fate of PCSCs, resulting in the enhanced osteogenic differentiation potential both and . PCSCs were isolated from the ring of La-Croix extracted from polydactylism patient and identified through immunohistochemically staining using anti-FGFR-3 antibodies. Potential toxicity of IONPs toward PCSCs was assessed through cell viability, proliferation, and attachment assay, and the results demonstrated that IONPs exhibited excellent biocompatibility. After that, the effects of IONPs on osteogenic differentiation of PCSCs were evaluated and enhanced ALP activity, formation of mineralized nodule, and osteogenic-related genes expressions could be observed upon IONPs treatment. Moreover, bone regeneration assessment was performed using rabbit femur defects as a model. A novel methacrylated alginate and 4-arm poly (ethylene glycol)-acrylate (4A-PEGAcr)-based interpenetrating polymeric printable network (IPN) hydrogel was prepared for incorporation of IONPs-labeled PCSCs, where 4A-PEGAcr was the common component for three-dimensional (3D) printing. The implantation of IONPs-labeled PCSCs significantly accelerated the bone formation process, indicating that IONPs-labeled PCSCs could endow current scaffolds with excellent osteogenic ability. Together with the fact that the IONPs-labeled PCSCs-incorporated IPN hydrogel (PCSCs-hydrogels) was biosafety and printable, we believed that PCSCs-hydrogels with enhanced osteogenic bioactivity could enrich the stem cell-based therapeutic strategies for bone tissue regeneration.
智能生物材料与基于干细胞的治疗策略相结合，为骨组织再生领域带来了创新。然而，对于软骨前体细胞（PCSCs）的了解却很少，这种细胞可作为种子细胞，并与生物活性支架结合用于骨缺损的重建组织治疗。在此，采用氧化铁纳米颗粒（IONPs）来调节PCSCs的命运，从而增强其在体内和体外的成骨分化潜能。从多指患者切除的La-Croix环中分离出PCSCs，并使用抗FGFR-3抗体通过免疫组织化学染色进行鉴定。通过细胞活力、增殖和附着试验评估IONPs对PCSCs的潜在毒性，结果表明IONPs具有优异的生物相容性。在此之后，评估了IONPs对PCSCs成骨分化的影响，经IONPs处理后可观察到碱性磷酸酶（ALP）活性增强、矿化结节形成以及成骨相关基因表达。此外，以兔股骨缺损为模型进行了骨再生评估。制备了一种新型的基于甲基丙烯酸化海藻酸盐和四臂聚（乙二醇）-丙烯酸酯（4A-PEGAcr）的互穿聚合物可打印网络（IPN）水凝胶，用于包载IONPs标记的PCSCs，其中4A-PEGAcr是三维（3D）打印的常用组分。IONPs标记的PCSCs植入显著加速了骨形成过程，表明IONPs标记的PCSCs可赋予当前支架优异的成骨能力。鉴于IONPs标记的PCSCs包载的IPN水凝胶（PCSCs-水凝胶）具有生物安全性且可打印，我们认为具有增强成骨生物活性的PCSCs-水凝胶可丰富基于干细胞的骨组织再生治疗策略。
