School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.
ACS Nano. 2023 Sep 12;17(17):17131-17147. doi: 10.1021/acsnano.3c04816. Epub 2023 Aug 16.
Dynamic hydrogels have attracted enormous interest for bone tissue engineering as they demonstrate reversible mechanics to better mimic biophysical cues of natural extracellular matrix (ECM) compared to traditional static hydrogels. However, the facile development of therapeutic dynamic hydrogels that simultaneously recapitulate the filamentous architecture of the ECM of living tissues and induce both osteogenesis and angiogenesis to augment vascularized bone regeneration remains challenging. Herein, we report a dual nanoengineered DNA dynamic hydrogel developed through the supramolecular coassembly of amyloid fibrils and clay nanosheets with DNA strands. The nanoengineered ECM-like fibrillar hydrogel network is facilely formed without a complicated and tedious molecular synthesis. Amyloid fibrils together with clay nanosheets synergistically enhance the mechanical strength and stability of the dynamic hydrogel and, more remarkably, endow the matrix with an array of tunable features, including shear-thinning, injectability, self-healing, self-supporting, and 3D printable properties. The QK peptide is further chemically grafted onto amyloid fibrils, and its sustainable release from the hydrogel matrix stimulates the tube formation and migration with human umbilical vein endothelial cells. Meanwhile, the nanoengineered hydrogel matrix promotes osteogenic differentiation of bone marrow mesenchymal stem cells due to the sustainable release of Si and Mg derived from clay nanosheets. Furthermore, the manipulation of enhanced vascularized bone regeneration by the dynamic hydrogel is revealed in a rat cranial bone defect model. This dual nanoengineered strategy envisions great promise in developing therapeutic dynamic hydrogels for improved and customizable bone regeneration.
动态水凝胶因其具有可恢复的机械性能而在骨组织工程中引起了极大的兴趣，与传统的静态水凝胶相比，它们可以更好地模拟天然细胞外基质 (ECM) 的生物物理线索。然而，开发具有治疗作用的动态水凝胶，同时再现活组织 ECM 的丝状结构，并诱导成骨和血管生成以增强血管化骨再生，仍然具有挑战性。在此，我们报告了一种通过淀粉样纤维和粘土纳米片与 DNA 链的超分子共组装开发的双重纳米工程 DNA 动态水凝胶。纳米工程 ECM 样纤维状水凝胶网络易于形成，而无需复杂和繁琐的分子合成。淀粉样纤维与粘土纳米片协同增强了动态水凝胶的机械强度和稳定性，更显著的是，赋予了基质一系列可调特性，包括剪切稀化、可注射性、自修复、自支撑和 3D 可打印性。QK 肽进一步化学接枝到淀粉样纤维上，其从水凝胶基质中的持续释放刺激了人脐静脉内皮细胞的管状形成和迁移。同时，由于粘土纳米片持续释放 Si 和 Mg，纳米工程水凝胶基质促进了骨髓间充质干细胞的成骨分化。此外，通过大鼠颅骨缺损模型揭示了动态水凝胶对增强血管化骨再生的操控。这种双重纳米工程策略有望开发出具有治疗作用的动态水凝胶，以实现更好和可定制的骨再生。
