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酒石酸支化聚乙烯亚胺碳点通过成骨分化促进骨缺损修复。

Tartaric acid-branched polyethyleneimine carbon dots promote repair of bone defect via osteogenic differentiation.

作者信息

Heo Soon Chul, Shin Hae Won, Lee Dong Joon, Garcia-Godoy Franklin, Keum Bo Ram, Kwon Yong Hoon, Kim Hyung Joon

机构信息

Department of Oral Physiology, Periodontal Diseases Signaling Network Research Center, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.

Institute of Tissue Regeneration Engineering (ITREN), Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea.

出版信息

Regen Biomater. 2025 May 16;12:rbaf030. doi: 10.1093/rb/rbaf030. eCollection 2025.

Abstract

Treating bone defects is a critical challenge in regenerative medicine. Carbon nanomaterials, with their unique physicochemical properties, offer significant potential for enhancing bone regeneration. In this study, we developed tartaric acid (TA)-based carbon dots (CDs) by synthesizing TA with branched polyethyleneimine (bPEI). These TA-bPEI CDs were systematically evaluated to determine their effects on osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (BMSCs) and their capacity to repair calvarial defects in an model. Characterization of TA-bPEI CDs revealed a size of approximately 10 nm and a positive surface charge. The CDs exhibited fluorescence emission peaks between 464 and 506 nm under excitation wavelengths of 340-440 nm. Cytotoxicity assays demonstrated that TA-bPEI CDs maintained BMSC viability at concentrations up to 250 μg/ml. However, at concentrations of 500 μg/ml and above, apoptosis was induced. Treatment with TA-bPEI significantly enhanced osteogenic differentiation , as evidenced by increased expression of osteogenic-specific proteins such as Runx2, ALP, OCN and OPN. , the application of TA-bPEI CDs in a mouse calvarial defect model promoted robust new bone formation, reduced defect gaps, and improved bone morphometric parameters, including bone volume fraction and trabecular thickness. These results suggest that TA-bPEI CDs enhance osteogenesis by directly stimulating osteogenic differentiation and upregulating osteogenesis-specific genes. This study demonstrates the high potential of TA-bPEI CDs as a novel nanomaterial for bone regeneration applications.

摘要

治疗骨缺损是再生医学中的一项关键挑战。碳纳米材料凭借其独特的物理化学性质,在促进骨再生方面具有巨大潜力。在本研究中,我们通过将酒石酸(TA)与支链聚乙烯亚胺(bPEI)合成,开发了基于酒石酸的碳点(CDs)。对这些TA-bPEI CDs进行了系统评估,以确定它们对人骨髓间充质干细胞(BMSCs)成骨分化的影响及其在小鼠模型中修复颅骨缺损的能力。TA-bPEI CDs的表征显示其尺寸约为10纳米,表面带正电荷。在340 - 440纳米的激发波长下,这些CDs在464至506纳米之间呈现荧光发射峰。细胞毒性试验表明,TA-bPEI CDs在浓度高达250微克/毫升时能维持BMSC的活力。然而,在浓度为500微克/毫升及以上时,会诱导细胞凋亡。TA-bPEI处理显著增强了成骨分化,如成骨特异性蛋白Runx2、碱性磷酸酶(ALP)、骨钙素(OCN)和骨桥蛋白(OPN)表达增加所证明。此外,TA-bPEI CDs在小鼠颅骨缺损模型中的应用促进了强劲的新骨形成,缩小了缺损间隙,并改善了骨形态计量学参数,包括骨体积分数和小梁厚度。这些结果表明,TA-bPEI CDs通过直接刺激成骨分化和上调成骨特异性基因来增强成骨作用。本研究证明了TA-bPEI CDs作为一种用于骨再生应用的新型纳米材料具有很高的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe65/12098262/68bb2ddbb819/rbaf030f8.jpg

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