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Hydroxylapatite-collagen hybrid scaffold induces human adipose-derived mesenchymal stem cells to osteogenic differentiation in vitro and bone regrowth in patients.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2019-12-13 , DOI: 10.1002/sctm.19-0170
Elisa Mazzoni 1 , Antonio D'Agostino 2 , Maria Rosa Iaquinta 1 , Ilaria Bononi 1 , Lorenzo Trevisiol 2 , John Charles Rotondo 1 , Simone Patergnani 1, 3 , Carlotta Giorgi 1 , Michael J Gunson 4 , G William Arnett 4, 5 , Pier Francesco Nocini 2 , Mauro Tognon 1 , Fernanda Martini 1
Affiliation  

Tissue engineering‐based bone graft is an emerging viable treatment modality to repair and regenerate tissues damaged as a result of diseases or injuries. The structure and composition of scaffolds should modulate the classical osteogenic pathways in human stem cells. The osteoinductivity properties of the hydroxylapatite‐collagen hybrid scaffold named Coll/Pro Osteon 200 were investigated in an in vitro model of human adipose mesenchymal stem cells (hASCs), whereas the clinical evaluation was carried out in maxillofacial patients. Differentially expressed genes (DEGs) induced by the scaffold were analyzed using the Osteogenesis RT2 PCR Array. The osteoinductivity potential of the scaffold was also investigated by studying the alkaline phosphatase (ALP) activity, matrix mineralization, osteocalcin (OCN), and CLEC3B expression protein. Fifty patients who underwent zygomatic augmentation and bimaxillary osteotomy were evaluated clinically, radiologically, and histologically during a 3‐year follow‐up. Among DEGs, osteogenesis‐related genes, including BMP1/2, ALP, BGLAP, SP7, RUNX2, SPP1, and EGFR, which play important roles in osteogenesis, were found to be upregulated. The genes to cartilage condensation SOX9, BMPR1B, and osteoclast cells TNFSF11 were detected upregulated at every time point of the investigation. This scaffold has a high osteoinductivity revealed by the matrix mineralization, ALP activity, OCN, and CLEC3B expression proteins. Clinical evaluation evidences that the biomaterial promotes bone regrowth. Histological results of biopsy specimens from patients showed prominent ossification. Experimental data using the Coll/Pro Osteon 200 indicate that clinical evaluation of bone regrowth in patients, after scaffold implantation, was supported by DEGs implicated in skeletal development as shown in “in vitro” experiments with hASCs.

中文翻译:

羟基磷灰石-胶原混合支架可诱导人脂肪来源的间充质干细胞在体外诱导成骨分化和使患者骨再生。

基于组织工程的骨移植是一种新兴的可行治疗方式,可以修复和再生由于疾病或受伤而受损的组织。支架的结构和组成应调节人干细胞中的经典成骨途径。在人脂肪间充质干细胞(hASCs)的体外模型中研究了名为Coll / Pro Osteon 200的羟基磷灰石-胶原混合支架的骨诱导特性,而在颌面部患者中进行了临床评估。使用成骨RT 2分析支架诱导的差异表达基因(DEG)。PCR阵列。还通过研究碱性磷酸酶(ALP)活性,基质矿化,骨钙蛋白(OCN)和CLEC3B表达蛋白来研究支架的骨诱导潜力。在3年的随访中,对50例行骨扩大和双颌截骨术的患者进行了临床,放射学和组织学评估。在DEG中,发现在成骨中起重要作用的BMP1 / 2,ALP,BGLAP,SP7,RUNX2,SPP1和EGFR等与成骨相关的基因被上调。在研究的每个时间点,都检测到了软骨凝聚SOX9,BMPR1B和破骨细胞TNFSF11的基因上调。通过基质矿化,ALP活性,OCN和CLEC3B表达蛋白显示该支架具有高骨诱导性。临床评估证明该生物材料可促进骨骼再生。患者活检标本的组织学结果显示出明显的骨化。使用Coll / Pro Osteon 200的实验数据表明,支架植入后,对患者骨再生的临床评估得到了涉及骨骼发育的DEG的支持,如hASC的“体外”实验所示。
更新日期:2019-12-13
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