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      A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair

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          Abstract

          The current effective method for treatment of spinal cord injury (SCI) is to reconstruct the biological microenvironment by filling the injured cavity area and increasing neuronal differentiation of neural stem cells (NSCs) to repair SCI. However, the method is characterized by several challenges including irregular wounds, and mechanical and electrical mismatch of the material-tissue interface. In the current study, a unique and facile agarose/gelatin/polypyrrole (Aga/Gel/PPy, AGP3) hydrogel with similar conductivity and modulus as the spinal cord was developed by altering the concentration of Aga and PPy. The gelation occurred through non-covalent interactions, and the physically crosslinked features made the AGP3 hydrogels injectable. In vitro cultures showed that AGP3 hydrogel exhibited excellent biocompatibility, and promoted differentiation of NSCs toward neurons whereas it inhibited over-proliferation of astrocytes. The in vivo implanted AGP3 hydrogel completely covered the tissue defects and reduced injured cavity areas. In vivo studies further showed that the AGP3 hydrogel provided a biocompatible microenvironment for promoting endogenous neurogenesis rather than glial fibrosis formation, resulting in significant functional recovery. RNA sequencing analysis further indicated that AGP3 hydrogel significantly modulated expression of neurogenesis-related genes through intracellular Ca 2+ signaling cascades. Overall, this supramolecular strategy produces AGP3 hydrogel that can be used as favorable biomaterials for SCI repair by filling the cavity and imitating the physiological properties of the spinal cord.

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          Highlights

          • A facile strategy was developed to fabricate AGP3 hydrogel satisfying physiological requirements.

          • AGP3 hydrogel promoted the differentiation of NSCs into neurons in vitro.

          • AGP3 hydrogel could activate endogenous neurogenesis to repair spinal cord injury.

          • AGP3 hydrogel modulated expression of neurogenesis-related genes in vitro.

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          Most cited references70

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          Advances in engineering hydrogels.

          Hydrogels are formed from hydrophilic polymer chains surrounded by a water-rich environment. They have widespread applications in various fields such as biomedicine, soft electronics, sensors, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. Further, the lack of dynamic cues and structural complexity within the hydrogels has limited their functions. Recent developments include engineering hydrogels that possess improved physicochemical properties, ranging from designs of innovative chemistries and compositions to integration of dynamic modulation and sophisticated architectures. We review major advances in designing and engineering hydrogels and strategies targeting precise manipulation of their properties across multiple scales.
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            Biomaterials. Electronic dura mater for long-term multimodal neural interfaces.

            The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. The soft implants extracted cortical states in freely behaving animals for brain-machine interface and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury.
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              Physical Double‐Network Hydrogel Adhesives with Rapid Shape Adaptability, Fast Self‐Healing, Antioxidant and NIR/pH Stimulus‐Responsiveness for Multidrug‐Resistant Bacterial Infection and Removable Wound Dressing

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                Author and article information

                Contributors
                Journal
                Bioact Mater
                Bioact Mater
                Bioactive Materials
                KeAi Publishing
                2452-199X
                23 December 2021
                September 2022
                23 December 2021
                : 15
                : 103-119
                Affiliations
                [a ]Department of Orthopedics Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China
                [b ]Orthopedics Research Institute of Zhejiang University, Hangzhou, 310009, Zhejiang, China
                [c ]Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, Zhejiang, China
                [d ]Ningbo Research Institute of Zhejiang University, Ningbo, 315100, Zhejiang, China
                [e ]State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310027, Zhejiang, China
                [f ]NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
                Author notes
                []Corresponding author. Department of Orthopedics Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China. zrcqx@ 123456zju.edu.cn
                [∗∗ ]Corresponding author. qianzhao@ 123456zju.edu.cn
                [∗∗∗ ]Corresponding author. Department of Orthopedics Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, Zhejiang, China. lifangcai@ 123456zju.edu.cn
                [1]

                These authors contributed equally to this work.

                Article
                S2452-199X(21)00575-2
                10.1016/j.bioactmat.2021.11.032
                8941182
                35386356
                fb56ea83-c22a-43ca-b7d4-fdad1472afc0
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 10 August 2021
                : 15 November 2021
                : 16 November 2021
                Categories
                Article

                conducting polymer,supramolecular hydrogels,biomimetic scaffolds,nerve regeneration,spinal cord injury

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