3D-printed oxygen-releasing scaffolds improve bone regeneration in mice.
3D-printed oxygen-releasing scaffolds improve bone regeneration in mice.
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DOI：
10.1016/j.biomaterials.2021.121318
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发表时间：
2022-01
期刊：
影响因子：
14
通讯作者：
Grayson WL
中科院分区：
文献类型：
--
作者：
Farris AL;Lambrechts D;Zhou Y;Zhang NY;Sarkar N;Moorer MC;Rindone AN;Nyberg EL;Perdomo-Pantoja A;Burris SJ;Free K;Witham TF;Riddle RC;Grayson WL
低氧 (O2) 扩散到大型组织工程支架中会阻碍移植细胞的治疗效果。为了克服这个问题，我们之前研究了中空的高压负载微型罐（μtanks）作为氧气储存器。为了适应骨再生，我们用聚乙烯醇和聚乳酸乙醇酸制造了可生物降解的μtank，并将它们嵌入形成3D打印的多孔聚ε-己内酯（PCL）-μtank支架。 PCL-μtank 支架装载有 300 – 500 psi 的纯 O2。当放置在大气压下时，支架会在长达 8 小时的时间内释放氧气。我们证实了缺氧对人脂肪干细胞（hASC）成骨分化的抑制作用，并且我们验证了μtank介导的短暂高氧对hASC没有毒性影响，这可能是由于内源性抗氧化调节基因的上调。我们通过将负载O2的、hASC接种的PCL-μtank支架植入小鼠颅骨缺损（直径4毫米×0.6毫米高）和在这两种情况下，我们观察到 O2 输送组的细胞外基质沉积增加，以及骨桥蛋白覆盖率和矿物质沉积增加。这项研究提供了证据，表明即使是 PCL-μtank 支架的短期 O2 输送也可能增强 hASC 介导的骨组织再生。
Low oxygen (O2) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (μtanks) to serve as O2 reservoirs. To adapt these for bone regeneration, we fabricated biodegradable μtanks from polyvinyl alcohol and poly(lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-ε-caprolactone (PCL)-μtank scaffolds. PCL-μtank scaffolds were loaded with pure O2 at 300 – 500 psi. When placed at atmospheric pressures, the scaffolds released O2 over a period of up to 8 hours. We confirmed the inhibitory effects of hypoxia on the osteogenic differentiation of human adipose-derived stem cells (hASCs and we validated that μtank-mediated transient hyperoxia had no toxic impacts on hASCs, possibly due to upregulation of endogenous antioxidant regulator genes. We assessed bone regeneration in vivo by implanting O2-loaded, hASC-seeded, PCL-μtank scaffolds into murine calvarial defects (4 mm diameters × 0.6 mm height) and subcutaneously (4 mm diameter × 8 mm height). In both cases we observed increased deposition of extracellular matrix in the O2 delivery group along with greater osteopontin coverages and higher mineral deposition. This study provides evidence that even short-term O2 delivery from PCL-μtank scaffolds may enhance hASC-mediated bone tissue regeneration.
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影响因子：
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