骨髓间充质干细胞/PRP/β-TCP/PCL生物打印构建物介导myc骨再生:快速缺损修复和初步临床疗效评估

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
IUBMB Life Pub Date : 2025-07-28 DOI:10.1002/iub.70036
Dinghao Luo, Zhaoyang Ran, Junxiang Wu, Lei Wang, Wen Wu, Kai Xie, Liang Deng, Yongqiang Hao
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引用次数: 0

摘要

骨缺损由于其形态的异质性和结构的复杂性给临床带来了巨大的挑战,需要结合结构适应性、生物力学稳定性和成骨潜力的再生策略。本研究采用生物3D打印技术制备了由骨髓间充质干细胞(BMSCs)、富血小板血浆(PRP)、聚己内酯(PCL)和β-磷酸三钙(β-TCP)组成的生物工程结构体。体外实验评估骨祖细胞增殖(CCK-8)、迁移(Transwell)、分化(ALP染色)和内皮小管形成(Matrigel测定)。采用兔股骨髁缺损模型,采用组织形态学分析(Masson染色和COL-1染色)评估体内骨再生。通过RNA测序和western blot分析探索其机制。临床验证包括对骨缺损患者的视觉模拟评分(VAS)评分和计算机断层扫描(CT)成像进行术前和术后评估。生物打印构建体显著增强了骨髓间充质干细胞的增殖(p < 0.01)、迁移(p < 0.0001)和ALP活性(p < 0.0001),同时促进了内皮小管的形成(p < 0.01)。在体内,BMSCs/PRP/PCL/β-TCP组在术后2周、1个月和6个月的Masson染色和I型胶原表达均高于对照组。临床VAS评分明显降低(术前3.33±1.63比术后0.50±0.84,p = 0.005),无严重并发症。PRP浓度依赖性上调MYC表达(mRNA: p < 0.0001;蛋白:p <; 0.0001),而MYC敲低则消除了prp诱导的ALP和RUNX2的表达,证实了MYC在成骨过程中的调节作用。总之,BMSCs/PRP/PCL/β-TCP生物打印构建体增强了myc介导的骨再生,在骨缺损修复方面具有良好的临床潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MYC-Mediated Osseous Regeneration via BMSCs/PRP/β-TCP/PCL Bioprinted Constructs: Rapid Defect Rehabilitation and Preliminary Clinical Efficacy Evaluation

Bone defects present significant clinical challenges due to their morphological heterogeneity and structural complexity, necessitating regenerative strategies that integrate structural adaptability, biomechanical stability, and osteogenic potential. In this study, a bioengineered construct composed of bone marrow mesenchymal stem cells (BMSCs), platelet-rich plasma (PRP), polycaprolactone (PCL), and β-tricalcium phosphate (β-TCP) was fabricated using 3D bioprinting. In vitro assays assessed osteoprogenitor cell proliferation (CCK-8), migration (Transwell), differentiation (ALP staining), and endothelial tubulogenesis (Matrigel assay). In vivo bone regeneration was evaluated using a rabbit femoral condyle defect model, with histomorphometric analysis (Masson and COL-1 staining). Mechanistic insights were explored via RNA sequencing and western blot analysis. Clinical validation included pre- and postoperative assessments of visual analog scale (VAS) scores and computed tomography (CT) imaging in patients with osseous defects. The bioprinted constructs significantly enhanced BMSCs proliferation (p < 0.01), migration (p < 0.0001), and ALP activity (p < 0.0001), while promoting endothelial tubulogenesis (p < 0.01). In vivo, the BMSCs/PRP/PCL/β-TCP group exhibited greater Masson staining and collagen type I expression than controls at 2 weeks, 1 month, and 6 months postoperatively. Clinically, VAS scores significantly decreased (3.33 ± 1.63 pre-op vs. 0.50 ± 0.84 post-op, p = 0.005) with no severe complications. PRP concentration-dependently upregulated MYC expression (mRNA: p < 0.0001; protein: p < 0.0001), while MYC knockdown abrogated PRP-induced ALP and RUNX2 expression, confirming MYC's regulatory role in osteogenesis. In conclusion, BMSCs/PRP/PCL/β-TCP bioprinted constructs enhance MYC-mediated bone regeneration, demonstrating promising clinical potential for bone defect repair.

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来源期刊
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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