Human bone marrow derived stem cell differentiation on 3D printed bioactive glass scaffolds

IF 4.5 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Siwei Li, Ali A. Mohammed, Amy Nommeots-Nomm, Xiaomeng Shi, Fadi Barrak, Agathe Heyraud, Julian R. Jones
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引用次数: 0

Abstract

Bioactive glass particles have previously been found to stimulate new bone growth in vivo and have a long clinical track record. The effect of bioactive glasses on human bone marrow derived stromal cells (hBMSCs) has not been clearly ascertained previously. Recently, 3D printed scaffolds of the ICIE16 glass composition (49.46 mol% SiO2, 36.6 mol% CaO, 6.6 mol% Na2O, 6.6 mol% K2O, 1.07 mol% P2O5) were found to produce high quality bone ingrowth in vivo in a rabbit model. This composition was chosen because it can be sintered into scaffolds without crystallisation. Here, we cultured hBMSCs on the 3D printed ICIE16 scaffolds to determine whether the scaffolds can support cell growth and osteogenic differentiation in vitro, with and without the presence of osteogenic supplements. This was compared to a control of culture media containing dissolution products of the bioactive glass scaffold. Our hypothesis was that the cells cultured on the scaffolds would undergo more osteogenic differentiation than cells cultured in media containing only the dissolution ions of the scaffolds, even without osteogenic supplements. hBMSCs cultured on ICIE16 scaffolds significantly increased expression of osteogenic differentiation and matrix formation markers, including Runx 2, Col1a1, Osteopontin, Osteocalcin and Alkaline Phosphatase, in comparison to monolayer cultures in basal conditions with bioactive glass dissolution products, at all time points up to 6 weeks. Six weeks was chosen as it is the time scale for bone fracture healing. The presence of osteogenic supplements appeared to have synergetic effects with 3D scaffolds, especially during early stages of osteogenic differentiation (week 2 and 4). By week 6, there was no significant difference in the expression of osteogenic markers by hBMSCs cultured on ICE16 scaffolds with and without osteogenic supplements. These findings support our hypothesis and highlight that the 3D structure and the dissolution of ICIE16 bioactive glass ionic products both independently influence osteogenic differentiation of hBMSCs.

Graphical Abstract

人类骨髓干细胞在3D打印生物活性玻璃支架上的分化
生物活性玻璃颗粒以前被发现可以刺激体内新骨的生长,并且有很长的临床记录。生物活性玻璃对人骨髓间质细胞(hBMSCs)的影响尚未得到明确的证实。最近,3D打印的ICIE16玻璃成分(49.46 mol% SiO2, 36.6 mol% CaO, 6.6 mol% Na2O, 6.6 mol% K2O, 1.07 mol% P2O5)支架在兔模型中获得了高质量的骨长入。选择这种组合物是因为它可以烧结成支架而不结晶。在这里,我们在3D打印的ICIE16支架上培养hBMSCs,以确定支架是否能够在体外支持细胞生长和成骨分化,无论是否存在成骨补充剂。这与含有生物活性玻璃支架溶解产物的培养基对照进行了比较。我们的假设是,在支架上培养的细胞比在只含有支架溶解离子的培养基中培养的细胞有更多的成骨分化,即使没有成骨补充剂。在6周内的所有时间点,与具有生物活性玻璃溶解产物的基础条件下单层培养相比,在ICIE16支架上培养的hBMSCs显著增加了成骨分化和基质形成标志物的表达,包括runx2、Col1a1、骨桥蛋白、骨钙素和碱性磷酸酶。选择6周作为骨折愈合的时间尺度。成骨补充剂的存在似乎与3D支架具有协同作用,特别是在成骨分化的早期阶段(第2周和第4周)。到第6周,在ICE16支架上培养的hBMSCs,在添加和不添加成骨补充剂的情况下,成骨标志物的表达无显著差异。这些发现支持了我们的假设,并强调了ICIE16生物活性玻璃离子产物的三维结构和溶解都独立影响hBMSCs的成骨分化。图形抽象
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来源期刊
Journal of Materials Science: Materials in Medicine
Journal of Materials Science: Materials in Medicine 工程技术-材料科学:生物材料
CiteScore
8.00
自引率
0.00%
发文量
73
审稿时长
3.5 months
期刊介绍: The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.
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