Effects of scaffold microstructure and low intensity pulsed ultrasound on chondrogenic differentiation of human mesenchymal stem cells

Effects of scaffold microstructure and low intensity pulsed ultrasound on chondrogenic differentiation of human mesenchymal stem cells
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DOI:
10.1002/bit.26480
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发表时间:
2018-02-01
影响因子:
3.8
通讯作者:
Sarkar, Kausik
Sarkar, Kausik
中科院分区:
工程技术2区
文献类型:
--
作者:
Aliabouzar, Mitra;Lee, Se-jun;Sarkar, Kausik

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研究了低强度脉冲超声 (LIPUS) 对接种在具有不同孔隙几何形状(方形和六角形通道)的 3D 打印聚乙二醇二丙烯酸酯 (PEG-DA) 支架上的人间充质干细胞 (hMSC) 增殖和软骨分化的影响。与实心或六边形多孔支架相比,具有方形孔的支架导致更高的 hMSC 生长和软骨分化。 1.5 MHz 时的最佳 LIPUS 参数为 100 mW/cm(2) 和 20% 占空比。 24 小时后,LIPUS 刺激使增殖增加高达 60%。对于软骨形成,我们评估了软骨组织中丰富的关键软骨生物标志物;糖胺聚糖 (GAG)、II 型胶原蛋白和总胶原蛋白。两周后,LIPUS 刺激使方形和六边形支架的 GAG 合成分别提高了 16% 和 11%。此外,3 周后,在 LIPUS 刺激下,相同模式下的 II 型胶原蛋白产量分别增加了 60% 和 40%。这些结果表明,已获得 FDA 批准用于治疗骨折的 LIPUS 刺激可能成为组织工程的高效工具,与 3D 打印和 hMSC 相结合,以再生受损的软骨组织。
The effects of low intensity pulsed ultrasound (LIPUS) on proliferation and chondrogenic differentiation of human mesenchymal stem cells (hMSCs) seeded on 3D printed poly-(ethylene glycol)-diacrylate (PEG-DA) scaffolds with varying pore geometries (square and hexagonal channels) were investigated. The scaffold with square pores resulted in higher hMSC growth and chondrogenic differentiation than a solid or a hexagonally porous scaffold. The optimal LIPUS parameters at 1.5 MHz were found to be 100 mW/cm(2) and 20% duty cycle. LIPUS stimulation increased proliferation by up to 60% after 24 hr. For chondrogenesis, we evaluated key cartilage biomarkers abundant in cartilage tissue; glycosaminoglycan (GAG), type II collagen and total collagen. LIPUS stimulation enhanced GAG synthesis up to 16% and 11% for scaffolds with square and hexagonal patterns, respectively, after 2 weeks. Additionally, type II collagen production increased by 60% and 40% for the same patterns, respectively under LIPUS stimulation after 3 weeks. These results suggest that LIPUS stimulation, which has already been approved by FDA for treatment of bone fracture, could be a highly efficient tool for tissue engineering in combination with 3D printing and hMSCs to regenerate damaged cartilage tissues.