Department of Biomaterials Science, Institute of Dentistry, University of Turku and City of Turku, Welfare Division, Turku, Finland.
Division of Clinical Neurosciences, Department of Neurosurgery, Turku Brain Injury Centre, Turku University Hospital and University of Turku, Turku, Finland.
J Tissue Eng Regen Med. 2020 Aug;14(8):1157-1168. doi: 10.1002/term.3056. Epub 2020 Jul 8.
Material-induced ossification is suggested as a suitable approach to heal large bone defects. Fiber-reinforced composite-bioactive glasses (FRC-BGs) display properties that could enhance the ossification of calvarial defects. Here, we analyzed the healing processes of a FRC-BG implant in vivo from the perspective of material-induced ossification. Histological analysis of the implant, which was removed 5 months after insertion, showed the formation of viable, noninflammatory mesenchymal tissue with newly-formed mineralized woven bone, as well as nonmineralized connective tissue with capillaries and larger blood vessels. The presence of osteocytes was detected within the newly generated bone matrix. To expand our understanding on the osteogenic properties of FRC-BG, we cultured human adipose tissue-derived mesenchymal stromal cells (AD-MSCs) in the presence of two different BGs (45S5 and S53P4) and Al O control. AD-MSCs grew and proliferated on all the scaffolds tested, as well as secreted abundant extracellular matrix, when osteogenic differentiation was appropriately stimulated. 45S5 and S53P4 induced enhanced expression of COL2A1, COL10A1, COL5A1 collagen subunits, and pro-osteogenic genes BMP2 and BMP4. The concomitant downregulation of BMP3 was also detected. Our findings show that FRC-BG can support the vascularization of the implant and the formation of abundant connective tissue in vivo. Specifically, BG 45S5 and BG S53P4 are suited to evoke the osteogenic potential of host mesenchymal stromal cells. In conclusion, FRC-BG implant demonstrated material-induced ossification both in vitro and in vivo.
材料诱导性成骨被认为是一种治疗大骨缺损的合适方法。纤维增强复合材料-生物活性玻璃（FRC-BG）具有增强颅骨缺损成骨的特性。在这里，我们从材料诱导性成骨的角度分析了 FRC-BG 植入物的体内愈合过程。植入物在插入 5 个月后被取出，对其进行组织学分析显示，形成了有活力、无炎症的间充质组织，并有新形成的矿化编织骨，以及无矿化的结缔组织，其中有毛细血管和较大的血管。在新生成的骨基质中检测到骨细胞的存在。为了扩展我们对 FRC-BG 成骨特性的理解，我们在两种不同的 BG（45S5 和 S53P4）和 Al O 对照存在的情况下培养人脂肪组织来源的间充质基质细胞（AD-MSCs）。AD-MSCs 在所有测试的支架上生长和增殖，并在适当刺激成骨分化时分泌丰富的细胞外基质。45S5 和 S53P4 诱导 COL2A1、COL10A1、COL5A1 胶原亚基和前成骨基因 BMP2 和 BMP4 的表达增强。同时还检测到 BMP3 的下调。我们的研究结果表明，FRC-BG 可以支持植入物的血管化和体内丰富结缔组织的形成。具体而言，BG 45S5 和 BG S53P4 适合激发宿主间充质基质细胞的成骨潜能。总之，FRC-BG 植入物在体外和体内均表现出材料诱导性成骨。
