3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration
3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration
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DOI：
10.1126/sciadv.abb5093
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发表时间：
2020-08-01
期刊：
影响因子：
13.6
通讯作者：
Kelly, Daniel J.
中科院分区：
文献类型：
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作者：
Freeman, Fiona E.;Pitacco, Pierluca;Kelly, Daniel J.
治疗性生长因子递送通常需要超生理剂量，这可能导致不期望的脱靶效应。本研究的目的是3D生物打印植入物含有时空定义的生长因子模式优化耦合血管生成和成骨。使用纳米粒子功能化生物墨水，可以打印具有不同生长因子模式和释放曲线的植入物，时间跨度从几天到几周。体内血管生成的程度取决于血管内皮生长因子（VEGF）的空间呈现。在含有VEGF空间梯度的植入物中观察到更高水平的血管侵袭，与那些均匀加载相同总量的蛋白质相比。含有VEGF梯度的印刷植入物，加上空间定义的BMP-2定位和释放动力学，加速了大骨缺损愈合，很少有异位骨形成。这证明了生长因子打印的潜力，一种公认的护理点治疗，用于严格控制组织再生。
Therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. The aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis. Using nanoparticle functionalized bioinks, it was possible to print implants with distinct growth factor patterns and release profiles spanning from days to weeks. The extent of angiogenesis in vivo depended on the spatial presentation of vascular endothelial growth factor (VEGF). Higher levels of vessel invasion were observed in implants containing a spatial gradient of VEGF compared to those homogenously loaded with the same total amount of protein. Printed implants containing a gradient of VEGF, coupled with spatially defined BMP-2 localization and release kinetics, accelerated large bone defect healing with little heterotopic bone formation. This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration.