Amyloid Fibril and Clay Nanosheet Dual-Nanoengineered DNA Dynamic Hydrogel for Vascularized Bone Regeneration

摘要

Dynamic hydrogels have attracted enormous interest forbone tissueengineering as they demonstrate reversible mechanics to better mimicbiophysical cues of natural extracellular matrix (ECM) compared totraditional static hydrogels. However, the facile development of therapeuticdynamic hydrogels that simultaneously recapitulate the filamentousarchitecture of the ECM of living tissues and induce both osteogenesisand angiogenesis to augment vascularized bone regeneration remainschallenging. Herein, we report a dual nanoengineered DNA dynamic hydrogeldeveloped through the supramolecular coassembly of amyloid fibrilsand clay nanosheets with DNA strands. The nanoengineered ECM-likefibrillar hydrogel network is facilely formed without a complicatedand tedious molecular synthesis. Amyloid fibrils together with claynanosheets synergistically enhance the mechanical strength and stabilityof the dynamic hydrogel and, more remarkably, endow the matrix withan array of tunable features, including shear-thinning, injectability,self-healing, self-supporting, and 3D printable properties. The QKpeptide is further chemically grafted onto amyloid fibrils, and itssustainable release from the hydrogel matrix stimulates the tube formationand migration with human umbilical vein endothelial cells. Meanwhile,the nanoengineered hydrogel matrix promotes osteogenic differentiationof bone marrow mesenchymal stem cells due to the sustainable releaseof Si4+ and Mg2+ derived from clay nanosheets.Furthermore, the manipulation of enhanced vascularized bone regenerationby the dynamic hydrogel is revealed in a rat cranial bone defect model.This dual nanoengineered strategy envisions great promise in developingtherapeutic dynamic hydrogels for improved and customizable bone regeneration.

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