Synergistic osteogenic and angiogenic effects of KP and QK peptides incorporated with an injectable and self-healing hydrogel for efficient bone regeneration.
Synergistic osteogenic and angiogenic effects of KP and QK peptides incorporated with an injectable and self-healing hydrogel for efficient bone regeneration.
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DOI：
10.1016/j.bioactmat.2022.02.011
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发表时间：
2022-12
影响因子：
18.9
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Li R;Zhou C;Chen J;Luo H;Li R;Chen D;Zou X;Wang W
在骨科实践中，由于创伤或手术造成的不规则缺损，传统的骨移植替代物难以适应。因此，可注射水凝胶由于其适应性和微创性，在骨修复中引起了越来越多的兴趣。但在操作过程中出现的不可控扩散或机械故障仍然是一个有待解决的问题。此外，为了实现带血管的骨再生，应采用成骨和血管生成生长因子的替代品，以避免免疫原性和成本高的问题。本研究开发了一种新型的可注射自愈水凝胶系统（GMO水凝胶），该系统负载KP和QK肽，用于促进不规则骨小缺损的血管化再生。明胶甲基丙烯酰和氧化右旋糖酐之间的动态亚胺键使转基因水凝胶具有自愈和剪切变薄的能力，从而具有良好的注射性和适应性。通过光聚合封闭的GelMA，转基因水凝胶进一步增强，从而更适合骨再生。此外，成骨肽KP和血管生成肽QK通过希夫碱反应拴在转基因水凝胶上，形成所需的释放谱。在体外实验中，该复合水凝胶能显著提高骨髓间充质干细胞的成骨分化和huvec的血管生成能力。在体内，转基因生物水凝胶中的KP和QK在促进大鼠颅骨新骨形成方面表现出显著的协同作用。总的来说，KP和QK负载的转基因生物水凝胶是可注射的和自愈合的，这可以作为一种有效的方法，通过微创方法进行血管化骨再生。成功制备了一种具有良好注射性能和自愈性能的动态水凝胶体系（转基因水凝胶）。选择成骨肽（KP）和血管生成肽（QK）作为BMP2/VEGF的替代品，并将其固定在转基因生物水凝胶上。肽负载的转基因生物水凝胶在体外和体内均能显著促进骨生成和血管生成。本研究为微创血管化骨再生提供了一种有效的方法。
Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute. Therefore, the injectable hydrogels have attracted an increasing interest for bone repair because of their fittability and mini-invasivity. However, the uncontrollable spreading or mechanical failures during its manipulation remain a problem to be solved. Moreover, in order to achieve vascularized bone regeneration, alternatives of osteogenic and angiogenic growth factors should be adopted to avoid the problem of immunogenicity and high cost. In this study, a novel injectable self-healing hydrogel system (GMO hydrogel) loaded with KP and QK peptides had been developed for enhancing vascularized regeneration of small irregular bone defect. The dynamic imine bonds between gelatin methacryloyl and oxidized dextran provided the GMO hydrogel with self-healing and shear-thinning abilities, which led to an excellent injectability and fittability. By photopolymerization of the enclosed GelMA, GMO hydrogel was further strengthened and thus more suitable for bone regeneration. Besides, the osteogenic peptide KP and angiogenic peptide QK were tethered to GMO hydrogel by Schiff base reaction, leading to desired releasing profiles. In vitro, this composite hydrogel could significantly improve the osteogenic differentiation of BMSCs and angiogenesis ability of HUVECs. In vivo, KP and QK in the GMO hydrogel demonstrated a significant synergistic effect in promoting new bone formation in rat calvaria. Overall, the KP and QK loaded GMO hydrogel was injectable and self-healing, which can be served as an efficient approach for vascularized bone regeneration via a minimally invasive approach. A dynamic hydrogel system(GMO hydrogel) with excellent injectable and self-healing performance was successfully fabricated developed. Osteogenic (KP) and angiogenic (QK) peptides were chosen as alternatives for BMP2/VEGF and were tethered to the GMO hydrogel. The peptide loaded GMO hydrogel could significantly improve osteogenesis and angiogenesis in vitro and in vivo. This study provided an efficient approach for vascularized bone regeneration in a minimally invasive way.
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DOI：
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发表时间：
2020-07-01
影响因子：
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影响因子：
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