Despite an increasing number of tissue-engineered scaffolds have been developing for bone regeneration,simple and universal fabrication of biomimetic bone microstructure to repair full-thickness bone defects remains a...Despite an increasing number of tissue-engineered scaffolds have been developing for bone regeneration,simple and universal fabrication of biomimetic bone microstructure to repair full-thickness bone defects remains a challenge and an acute clinical demand due to the negligence of microstructural differences within the cortex of cancellous bone.In this work,a biomimetic sandwich-layered PACG-CS@Mn(Ⅲ)hydrogel(SL hydrogel)was facilely fabricated in an end-tail soaking strategy by simply post-crosslinking of poly(acryloyl 2-glycine)-chitosan(PACG-CS)composite hydrogel using trivalent manganese solutions.Taking the merits of in-situ formation and flexible adjustment of chain entanglements,hydrogen bonds and metal chelate interactions,SL hydrogel with sandwich-like three-layered structures and anisotropic mechanical performance was easily customized through control of the manganese concentration and soaking time in fore-and-aft sides,simulating the structurally and mechanically biomimetic characteristics of cortical and cancellous bone.Furthermore,the produced SL hydrogel also demonstrated favorable biocompatibility and enhanced MnSOD activity via a peroxidase-like reaction,which enabled the excellent radical scavenging efficiency and anti-inflammatory regulation for facilitating the activity,proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In vivo studies further revealed that these SL hydrogels achieved restrictive pro-vascular regeneration through their stratified structure,thereby promoting the differentiation of osteoblasts.Simultaneously,the mechanical cues of stratified structure could mediate macrophage phenotype transitions in accordance with stem cell-osteoblast differentiation process via the PI3K-AKT pathway,resulting in robust osteogenesis and high-quality bone reconstruction.This facile yet efficient strategy of turning anisotropic hydrogel offers a promising alternative for full-thickness repair of bone defects,which is also significantly imperative to achieve high-performance scaffolds with specific usage requirements and expand their clinic applicability in more complex anisotropic tissues.展开更多
基金supported by the National Natural Science Foundation of China(52373162,82002291 and 51973226)Beijing Natural Science Foundation(L244037)+1 种基金National Key R&D program of China(2020YFC2004906)Key Program of National Natural Science Foundation of China(81930069).
文摘Despite an increasing number of tissue-engineered scaffolds have been developing for bone regeneration,simple and universal fabrication of biomimetic bone microstructure to repair full-thickness bone defects remains a challenge and an acute clinical demand due to the negligence of microstructural differences within the cortex of cancellous bone.In this work,a biomimetic sandwich-layered PACG-CS@Mn(Ⅲ)hydrogel(SL hydrogel)was facilely fabricated in an end-tail soaking strategy by simply post-crosslinking of poly(acryloyl 2-glycine)-chitosan(PACG-CS)composite hydrogel using trivalent manganese solutions.Taking the merits of in-situ formation and flexible adjustment of chain entanglements,hydrogen bonds and metal chelate interactions,SL hydrogel with sandwich-like three-layered structures and anisotropic mechanical performance was easily customized through control of the manganese concentration and soaking time in fore-and-aft sides,simulating the structurally and mechanically biomimetic characteristics of cortical and cancellous bone.Furthermore,the produced SL hydrogel also demonstrated favorable biocompatibility and enhanced MnSOD activity via a peroxidase-like reaction,which enabled the excellent radical scavenging efficiency and anti-inflammatory regulation for facilitating the activity,proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).In vivo studies further revealed that these SL hydrogels achieved restrictive pro-vascular regeneration through their stratified structure,thereby promoting the differentiation of osteoblasts.Simultaneously,the mechanical cues of stratified structure could mediate macrophage phenotype transitions in accordance with stem cell-osteoblast differentiation process via the PI3K-AKT pathway,resulting in robust osteogenesis and high-quality bone reconstruction.This facile yet efficient strategy of turning anisotropic hydrogel offers a promising alternative for full-thickness repair of bone defects,which is also significantly imperative to achieve high-performance scaffolds with specific usage requirements and expand their clinic applicability in more complex anisotropic tissues.
