Enhancement and orchestration of osteogenesis and angiogenesis by a dual-modular design of growth factors delivery scaffolds and 26SCS decoration
Enhancement and orchestration of osteogenesis and angiogenesis by a dual-modular design of growth factors delivery scaffolds and 26SCS decoration
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通过生长因子递送支架和 26SCS 装饰的双模块设计增强和协调成骨和血管生成
DOI：
10.1016/j.biomaterials.2019.119645
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发表时间：
2020-02-01
期刊：
影响因子：
14
通讯作者：
Liu, Changsheng
中科院分区：
文献类型：
--
作者：
Tang, Wei;Yu, Yuanman;Liu, Changsheng
保持生长因子（GF）的生物活性并模拟其体内供应模式是基于GF的骨移植物发展的挑战。在这项研究中，我们开发了一种2-N，6-O-硫酸化壳聚糖（26 SCS）功能化的双模块支架，该支架由具有分级多孔结构的介孔生物活性玻璃（MBG）（模块I）和原位固定在模块I的中空通道中的GelMA水凝胶柱（模块II）组成，能够实现成骨rhBMP-2和血管生成VEGF的差异化递送模式。通过将rhBMP-2固定在模块I中并将VEGF包埋在模块II中，实现了由最初的高浓度VEGF随后随时间降低浓度和rhBMP-2的较慢/可持续释放组成的组合释放曲线。系统的体外和体内研究证明，骨生成和血管生成的两个耦合过程是精心策划的，并且都归因于特定的GFs递送模式和26 SCS装饰而增强。26 SCS不仅能增强GFs的生物活性，而且能降低noggin的拮抗作用。这项研究强调了区分不同GFs的递送模式的重要性，并可能揭示基于生长因子的骨移植物的未来设计。
Preserving the bioactivity of growth factors (GFs) and mimicking their in vivo supply patterns are challenging in the development of GFs-based bone grafts. In this study, we develop a 2-N, 6-O-sulfated chitosan (26SCS) functionalized dual-modular scaffold composed of mesoporous bioactive glass (MBG) with hierarchical porous structures (module I) and GelMA hydrogel columns (module II) in situ fixed in hollowed channels of the module I, which is capable of realizing differentiated delivery modes for osteogenic rhBMP-2 and angiogenic VEGF. A combinational release profile consisting of a high concentration of VEGF initially followed by a decreasing concentration over time, and a slower/sustainable release of rhBMP-2 is realized by immobilizing rhBMP-2 in module I and embedding VEGF in module II. Systematic in vitro and in vivo studies prove that the two coupled processes of osteogenesis and angiogenesis are well-orchestrated and both enhanced ascribed to the specific GFs delivery modes and 26SCS decoration. 26SCS not only enhances the GFs' bioactivity but also decreases antagonism effects of noggin. This study highlights the importance of differentiating the delivery pattern of different GFs and likely sheds light on the future design of growth factor-based bone grafts.