ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration  

作　　者：Guanglong Li Fei Gao Donglei Yang Lu Lin Weijun Yu Jiaqi Tang Ruhan Yang Min Jin Yuting Gu Pengfei Wang Eryi Lu 

机构地区：[1]Department of Stomatology,Renji Hospital,Shanghai Jiao Tong University School of Medicine,160 Pujian Road,Shanghai,200127,China [2]Institute of Molecular Medicine,Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine,Renji Hospital,Shanghai Jiao Tong University School of Medicine,160 Pujian Road,Shanghai,200127,China

出　　处：《Bioactive Materials》2024年第12期241-256,共16页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China(Grant Nos.52171075,52103172,82271589);Science and Technology Commission of Shanghai Municipality(Grant Nos.21DZ2294700,21ZR1439400);Opening Project of Shanghai Key Laboratory of Orthopaedic Implant(Grant No.KFKT2021001);the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant No.2023-JKCS-14);Incubating Program for National Program of Renji Hospital,Shanghai Jiao Tong University School of Medicine(Grant No.RJTJ23-PY-053);“Clinic Plus”Outstanding Project of Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine(Grant No.2021ZYA009).

摘　　要：Bioactive hydrogel materials have great potential for applications in bone tissue engineering.However,fabrication of functional hydrogels that mimic the natural bone extracellular matrix(ECM)remains a challenge,because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis.Inspired by the features of ECM,we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl(GelMA)and deoxyribonucleic acid(DNA).Within the composite hydrogel,the GelMA network serves as the backbone for mechanical and biological stability,whereas the DNA network realizes dynamic capabilities(e.g.,stress relaxation),thereby promoting cell proliferation and osteogenic differentiation.Furthermore,functional aptamers(Apt19S and AptV)are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells(BMSCs)and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis.Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs,promote osteogenic differentiation by activating focal adhesion kinase(FAK)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/β-Catenin signaling pathway,and eventually enhance vascularized bone regeneration.This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.

关 键 词：Composite hydrogel DNA hydrogel Stress relaxation OSTEOGENESIS VASCULARIZATION 

分 类 号：TQ427.26[化学工程] R318[医药卫生—生物医学工程]