Wen Zhang , Yang Liu , Yu Wu , Zhicun Wang , Xiyu Liu , Qinsheng Hu , Li Yang , Cheng Hu , Yunbing Wang
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引用次数: 0
Abstract
Millions of individuals worldwide suffer from ischemic stroke (IS). The focal hypo-perfused brain brings about hostile pathological environment, which further restricts endogenous neurogenesis post-stroke. In this work, we report an ROS-triggered hyaluronic acid (HA) and platelet lysates (pls) composite biomimetic hydrogel soft scaffold (pls gel) encapsulating matrix metalloproteinase (MMPs)-responsive triglycerol monostearate nanoparticles loaded with docosahexaenoic acid (TGMS@DHA, TD). Pls gel was chosen to be the hydrogel matrix to mimic brain extracellular matrix (ECM) to provide physical support for cell infiltration and accelerate angiogenesis as a growth factors (GFs) box. The borate ester bonded hydrogel could respond to reactive oxygen species and relieve oxidative stress. The loaded TD nanoparticles could be enzymatically cleaved by overexpressed MMPs in cerebral infarcted site, which could improve the adverse effects triggered by overexpressed MMPs. DHA with rich unsaturated bonds was proven that not only inhibit neuroinflammatory and oxidative stress, but also take part in promote neurogenesis. In brief, the ROS-triggered hydrogel scaffold pls gel@TD created an optimized microenvironment to manipulate the survival and differentiation of neural stem cells and promote endogenous regenerative repair processes. The in vitro results exhibited the biomimetic soft scaffold eliminated oxygen-glucose deprivation-derived free radical, saved mitochondrial dysfunction, reduced neuronal apoptosis, and promoted neovascularization. In the mice focal IS model, the biomimetic hydrogel scaffold regulated pathological environment in the ischemic site and induced migration and differentiation of endogenous neural stem cells, consequently relieved neuron ischemia injury. During the long-term observation, the hydrogel improved mice neurobehavioral functions. In conclusion, the hydrogel soft scaffold pls gel@TD was demonstrated to have promising therapeutic effects on remodeling pathological environment by transforming the hostile state into a pro-regenerative one in the infarct site, consequently promoting endogenous regenerative repair processes.
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.