MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration.
MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration.
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3D打印生成的MicroRNA激活水凝胶支架可加速骨再生
DOI：
10.1016/j.bioactmat.2021.08.034
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发表时间：
2022-04
影响因子：
18.9
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Pan T;Song W;Xin H;Yu H;Wang H;Ma D;Cao X;Wang Y
骨缺损仍然是人类健康的主要威胁，骨组织再生已成为世界范围内突出的临床需求。microRNA （miRNA）治疗与3D打印支架的结合一直是一个挑战。它可以模拟生理性骨愈合过程，生物可降解支架逐渐被新生组织取代，miRNA的持续释放在创造最佳成骨微环境中起着至关重要的作用，从而实现有希望的骨修复效果。然而，两个关键因素-支架降解行为和miRNA释放谱-在成骨和骨形成中的平衡仍然知之甚少。在此，我们构建了一系列由3D打印生成的具有不同交联度的miRNA活化水凝胶支架（MAHSs），在体外和体内筛选支架降解与miRNA释放之间的相互作用对骨诱导活性的影响。虽然交联度较低的mahs （MAHS-0和MAHS-0.25）在缓释谱中释放了更多的miR-29b，但它们降解得太快，无法为细胞和组织的生长提供长期的支持。相反，虽然高交联度的mahs （MAHS-1和MAHS-2.5）降解缓慢导致miR-29b释放不足，但其适应性降解速率使其长期具有更有效的骨诱导行为。MAHS-1具有最匹配的降解率和miR-29b释放特性，被确定为加速骨再生的首选mahs。该研究表明，支架降解行为与生物活性因子释放之间的生物适应性平衡在骨再生中起着至关重要的作用。这些发现将为设计mirna及其他生物活性分子激活的组织再生支架提供有价值的参考。通过三维绘图技术逐层生成由明胶和海藻酸盐组成的三维多孔水凝胶支架，然后与Ca2+和不同浓度的GTA交联。随后将冻干后的支架浸入含有miR/NP的PBS中，通过干燥的水凝胶吸水来加载miR/NP。不同交联度的mahs分别用于体外成骨和体内成骨，本研究重点关注支架降解速率与miRNA释放谱之间的平衡。体外和体内hMSCs成骨过程中支架降解与miRNA释放的相互作用。第一个支持支架降解和miRNA释放谱之间生物适应性平衡的观点。
Bone defects remain a major threat to human health and bone tissue regeneration has become a prominent clinical demand worldwide. The combination of microRNA (miRNA) therapy with 3D printed scaffolds has always posed a challenge. It can mimic physiological bone healing processes, in which a biodegradable scaffold is gradually replaced by neo-tissue, and the sustained release of miRNA plays a vital role in creating an optimal osteogenic microenvironment, thus achieving promising bone repair outcomes. However, the balance between two key factors - scaffold degradation behavior and miRNA release profile - on osteogenesis and bone formation is still poorly understood. Herein, we construct a series of miRNA-activated hydrogel scaffolds (MAHSs) generated by 3D printing with different crosslinking degree to screened the interplay between scaffold degradation and miRNA release in the osteoinduction activity both in vitro and in vivo. Although MAHSs with a lower crosslinking degree (MAHS-0 and MAHS-0.25) released a higher amount of miR-29b in a sustained release profile, they degraded too fast to provide prolonged support for cell and tissue ingrowth. On the contrary, although the slow degradation of MAHSs with a higher crosslinking degree (MAHS-1 and MAHS-2.5) led to insufficient release of miR-29b, their adaptable degradation rate endowed them with more efficient osteoinductive behavior over the long term. MAHS-1 gave the most well-matched degradation rate and miR-29b release characteristics and was identified as the preferred MAHSs for accelerated bone regeneration. This study suggests that the bio-adaptable balance between scaffold degradation behavior and bioactive factors release profile plays a critical role in bone regeneration. These findings will provide a valuable reference about designing miRNAs as well as other bioactive molecules activated scaffold for tissue regeneration. 3D porous hydrogel scaffold consisting of gelatin and alginate is generated layer by layer through a 3D plotting technique, then crosslinked with Ca2+ and varying concentrations of GTA. The lyophilized scaffold is subsequently immersed in miR/NP-containing PBS to load miR/NP through water absorption by the dried hydrogels. MAHSs with different crosslinking degree are applied for osteogenesis in vitro and bone formation in vivo, and this study focuses on the balance between the scaffold degradation rate and miRNA release profile. The interplay between scaffold degradation and miRNA release in the osteogenesis of hMSCs both in vitro and in vivo. The first to support the notion that the bio-adaptable balance between scaffold degradation and miRNA release profile.
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影响因子：
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作者：
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