Hu Chen, Wanshun Wang, Yiming Yang, Beichen Zhang, Zefeng Li, Lingling Chen, Qiang Tu, Tao Zhang, Dingkun Lin, Honglei Yi, Hong Xia, Yao Lu
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引用次数: 0
Abstract
Utilizing drug-loaded hydrogels to restore nerve conductivity emerges as a promising strategy in the treatment of spinal cord injury (SCI). However, many of these hydrogels fail to deliver drugs on demand according to the dynamic SCI pathological features, resulting in poor functional recovery. Inspired by the post-SCI microenvironments, here we report a time-sequential and controllable drug delivery strategy using an injectable hydrogel responsive to reactive oxygen species (ROS) and matrix metalloproteinases (MMPs). This strategy includes two steps: first, the hydrogel responds to ROS and releases nanodrugs to scavenge ROS, thereby mitigating inflammation and protecting neurons from oxidative stress in the initial SCI stages; second, the accumulation of MMPs triggers the release of vascular endothelial growth factor from nanodrugs to promote angiogenesis and neural stem cell differentiation in the late stage of SCI. In two clinically relevant SCI models, a single injection of the hydrogel led to an efficient structural and functional recovery of SCI 6 weeks after the intervention. We observed less inflammation, fibrosis, and cavities but more angiogenesis and neurons in the hydrogel-treated injured spinal cord region compared with the untreated animals. The hydrogel exhibits mechanical strength and conductivity comparable to natural spinal cord, facilitating its further clinical translation.
期刊介绍:
Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.