Dinghao Luo, Zhaoyang Ran, Junxiang Wu, Lei Wang, Wen Wu, Kai Xie, Liang Deng, Yongqiang Hao
{"title":"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","authors":"Dinghao Luo, Zhaoyang Ran, Junxiang Wu, Lei Wang, Wen Wu, Kai Xie, Liang Deng, Yongqiang Hao","doi":"10.1002/iub.70036","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>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 (<i>p</i> < 0.01), migration (<i>p</i> < 0.0001), and ALP activity (<i>p</i> < 0.0001), while promoting endothelial tubulogenesis (<i>p</i> < 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, <i>p</i> = 0.005) with no severe complications. PRP concentration-dependently upregulated MYC expression (mRNA: <i>p</i> < 0.0001; protein: <i>p</i> < 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.</p>\n </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"77 7","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MYC-Mediated Osseous Regeneration via BMSCs/PRP/β-TCP/PCL Bioprinted Constructs: Rapid Defect Rehabilitation and Preliminary Clinical Efficacy Evaluation\",\"authors\":\"Dinghao Luo, Zhaoyang Ran, Junxiang Wu, Lei Wang, Wen Wu, Kai Xie, Liang Deng, Yongqiang Hao\",\"doi\":\"10.1002/iub.70036\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>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 (<i>p</i> < 0.01), migration (<i>p</i> < 0.0001), and ALP activity (<i>p</i> < 0.0001), while promoting endothelial tubulogenesis (<i>p</i> < 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, <i>p</i> = 0.005) with no severe complications. PRP concentration-dependently upregulated MYC expression (mRNA: <i>p</i> < 0.0001; protein: <i>p</i> < 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.</p>\\n </div>\",\"PeriodicalId\":14728,\"journal\":{\"name\":\"IUBMB Life\",\"volume\":\"77 7\",\"pages\":\"\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"IUBMB Life\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/iub.70036\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"IUBMB Life","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/iub.70036","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.