A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury

Wang, Chenggui; Wang, Min; Xia, Kaishun; Wang, Jingkai; Cheng, Feng; Shi, Kesi; Ying, Liwei; Yu, Chao; Xu, Haibin; Xiao, Shining; Liang, Chengzhen; Li, Fangcai; Lei, Bo; Chen, Qixin

doi:10.1016/j.bioactmat.2021.01.029

Cited by 71 publications

(57 citation statements)

References 55 publications

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“…Curcumin was encapsulated within the hybrid hydrogel, which could be released in a sustainable pattern. Several studies focus on synthesis of polymeric hydrogel of self-healing properties for treating SCI [ 38 ]. Advances in molecular science make it feasible by creating complicated molecular structures in order for multiple functions.…”

Section: Resultsmentioning

confidence: 99%

An injectable and self-healing hydrogel with controlled release of curcumin to repair spinal cord injury

Luo

Shi

et al. 2021

Bioactive Materials

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The harsh local micro-environment following spinal cord injury (SCI) remains a great challenge for neural regeneration. Local reconstitution of a favorable micro-environment by biocompatible scaffolds with desirable functions has thus been an area of concern. Herein, a hybrid hydrogel was developed using Fmoc-grafted chitosan (FC) and Fmoc peptide (FI). Dynamic reversible π-π stacking interactions of the fluorenyl rings enabled the FC/FI hybrid hydrogel to exhibit excellent injectable and self-healing properties, as characterized by visual appearances and rheological tests. Furthermore, the FC/FI hybrid hydrogel showed a slow and persistent release of curcumin (Cur), which was named as FC/FI-Cur hydrogel. In vitro studies confirmed that with the support of FC/FI-Cur hydrogel, neurite outgrowth was promoted, and Schwann cell (SC) migration away from dorsal root ganglia (DRG) spheres with enhanced myelination was substantiated. The FC/FI-Cur hydrogel well reassembled extracellular matrix at the lesion site of rat spinal cord and exerted outstanding effects in modulating local inflammatory reaction by regulating the phenotypes of infiltrated inflammatory cells. In addition, endogenous SCs were recruited in the FC/FI-Cur graft and participated in the remyelination process of the regenerated nerves. These outcomes favored functional recovery, as evidenced by improved hind limbs movement and enhanced electrophysiological properties. Thus, our study not only advanced the development of multifunctional hydrogels but also provided insights into comprehensive approaches for SCI repair.

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Section: Resultsmentioning

confidence: 99%

An injectable and self-healing hydrogel with controlled release of curcumin to repair spinal cord injury

Luo

Shi

et al. 2021

Bioactive Materials

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“…In-situ -forming injectable hydrogels as implantable biomaterials/devices have attracted tremendous attention because of their minimally invasive administration mode [ [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. In particular, thermosensitive and biodegradable hydrogels comprised of copolymers of hydrophobic polyesters, such as poly(lactic acid) (PLA), poly( ε -caprolactone) (PCL), poly(lactic acid- co -glycolic acid) (PLGA), poly( ε -caprolactone- co -glycolic acid) (PCGA), poly( ε -caprolactone- co -lactic acid) (PCLA), and hydrophilic poly(ethylene glycol) (PEG) are free-flowing polymer aqueous solutions at low or ambient temperature; however, they exhibit sol-gel transitions in response to the changes in temperature [ [31] , [32] , [33] , [34] , [35] , [36] ].…”

Section: Introductionmentioning

confidence: 99%

Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues

Wang

Chen

et al. 2021

Bioactive Materials

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It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo . Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.

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“…For example, compared to bolus EV injections, EV-functionalized polyethylene glycol hydrogels significantly enhanced liver regeneration by attenuating inflammation and apoptosis in a rat model of chronic liver fibrosis [14] . In a myocardial infarction rat model, EV-loaded peptide hydrogels were superior to EV bolus injection in increasing angiogenesis and reducing inflammation [15] . Bioscaffoldbased EV delivery may be more advantageous than traditional EV injections in improving retention and targeted delivery of EVs to the site of injury [10,12,16] .…”

mentioning

confidence: 96%

“…By integrating biochemistry and bioengineering principles, EV bioscaffold products have shown promising therapeutic outcomes in numerous medical studies, such as wound healing, tissue regeneration, vascularization, and angiogenesis [Figure 1] [8,13,17] . In addition, appropriate EV delivery systems have shown obvious advantages for further enhancing the function of EV modified bioscaffolds [15,18] . Therefore, future research may focus on further refinement of EV modified scaffolds, such as the loading and release mechanisms, the loading density and release profile, storage stability, and safety must be fully characterized before clinical applications.…”

mentioning

confidence: 99%

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Bioengineered extracellular vesicle-loaded bioscaffolds for therapeutic applications in regenerative medicine

Lazar¹,

Mor²,

Chen³

et al. 2021

EVCNA

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Extracellular vesicle (EV)-based technologies represent a new advancement for disease treatment. EVs can be administered systemically, injected into the injury site directly, or applied locally in conjunction with bioengineered implantable scaffolds. Matrix-bound vesicles (MBVs), a special class of vesicles localized in association with the extracellular matrix (ECM), have been identified as critical bioactive factors and shown to mediate significant regenerative functions of ECM scaffolds. Loading EVs onto bioscaffolds to mimic the MBV-ECM complex has been shown superior to EV bolus injection in recent in vivo studies, such as in providing enhanced tissue regeneration, EV retention rates, and healing efficacy. Different types of natural biomaterials, synthetic polymers, and ceramics have been developed for EV loading, and these EV functionalized biomaterials have been applied in different areas for disease treatment. The EV functionalized scaffolds can be designed to be biodegradable, off-the-shelf biomaterials as a delivery vehicle for EVs. Overall, the bioengineered EV-loaded bioscaffolds represent a promising approach for cell-free treatment in clinical applications.

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A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury

Cited by 71 publications

References 55 publications

An injectable and self-healing hydrogel with controlled release of curcumin to repair spinal cord injury

An injectable and self-healing hydrogel with controlled release of curcumin to repair spinal cord injury

Injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues

Bioengineered extracellular vesicle-loaded bioscaffolds for therapeutic applications in regenerative medicine

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