Engineering of an electrically charged hydrogel implanted into a traumatic brain injury model for stepwise neuronal tissue reconstruction

Tanikawa, Satoshi; Ebisu, Yuki; Sedlačík, Tomáš; Semba, Shingo; Nonoyama, Takayuki; Kurokawa, Takayuki; Hirota, Akira; Takahashi, Taiga; Yamaguchi, Kazushi; Imajo, Masamichi; Kato, Harunosuke; Nishimura, Toshiaki; Tanei, Zen‐ichi; Tsuda, Masumi; Nemoto, Tomomi; Gong, Jian Ping; Tanaka, Shinya

doi:10.1038/s41598-023-28870-z

Cited by 9 publications

(5 citation statements)

References 56 publications

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“…Therefore, the CCI-SA-sTBI model mimics resection of contused tissue to leave behind a tissue cavity, and the intracavitary delivery of 3D constructs represents a novel paradigm for assessing lesion volume deficits, cellular repair, biomaterial integration and cross-talk with native brain tissue. The (CS-A)CP hydrogel implanted animals demonstrated significantly accelerated recovery of forelimb motor function, 5-weeks after sTBI, which was likely mediated by the intralesional presence of neuroprotective and neuritogenic scaffolding [20,21,64,65]. Immunohistochemical analyses of perilesional tissue confirmed that the hydrogel implant was able to prevent neuronal as well as axonal loss and demonstrated greater synaptic vesicle presence, indicating tissue recovery.…”

Section: Discussionmentioning

confidence: 86%

Neuritogenic glycosaminoglycan hydrogels promote functional recovery after severe traumatic brain injury

Gonsalves,

Sun,

Chopra

et al. 2024

J. Neural Eng.

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Objective. Severe traumatic brain injury (sTBI) induced neuronal loss and brain atrophy contribute significantly to long-term disabilities. Brain extracellular matrix (ECM) associated chondroitin sulfate (CS) glycosaminoglycans promote neural stem cell (NSC) maintenance, and CS hydrogel implants have demonstrated the ability to enhance neuroprotection, in preclinical sTBI studies. However, the ability of neuritogenic chimeric peptide (CP) functionalized CS hydrogels in promoting functional recovery, after controlled cortical impact (CCI) and suction ablation (SA) induced sTBI, has not been previously demonstrated. We hypothesized that neuritogenic (CS)CP hydrogels will promote neuritogenesis of human NSCs, and accelerate brain tissue repair and functional recovery in sTBI rats. Approach. We synthesized chondroitin 4-O sulfate (CS-A)CP, and 4,6-O-sulfate (CS-E)CP hydrogels, using strain promoted azide-alkyne cycloaddition (SPAAC), to promote cell adhesion and neuritogenesis of human NSCs, in vitro; and assessed the ability of (CS-A)CP hydrogels in promoting tissue and functional repair, in a novel CCI-SA sTBI model, in vivo. Main Results. Results indicated that (CS-E)CP hydrogels significantly enhanced human NSC aggregation and migration via focal adhesion kinase complexes, when compared to NSCs in (CS-A)CP hydrogels, in vitro. In contrast, NSCs encapsulated in (CS-A)CP hydrogels differentiated into neurons bearing longer neurites and showed greater spontaneous activity, when compared to those in (CS-E)CP hydrogels. The intracavitary implantation of (CS-A)CP hydrogels, acutely after CCI-SA-sTBI, prevented neuronal and axonal loss, as determined by immunohistochemical analyses. (CS-A)CP hydrogel implanted animals also demonstrated the significantly accelerated recovery of ‘reach-to-grasp’ function when compared to sTBI controls, over a period of 5-weeks. Significance. These findings demonstrate the neuritogenic and neuroprotective attributes of (CS)CP “click” hydrogels, and open new avenues for using modified CS biorthogonal handles to develop tissue engineered implants for sTBI repair.

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Section: Discussionmentioning

confidence: 86%

Neuritogenic glycosaminoglycan hydrogels promote functional recovery after severe traumatic brain injury

Gonsalves,

Sun,

Chopra

et al. 2024

J. Neural Eng.

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“…During ischemic damage, the brain’s blood supply is reduced, leading to the loss of neuroglial cells, tissue framework, and extracellular matrix [ 69 ].…”

Section: The Nervous Systemmentioning

confidence: 99%

Injectable Hydrogels for Nervous Tissue Repair—A Brief Review

Politrón-Zepeda,

Fletes-Vargas,

Rodríguez-Rodríguez

2024

Gels

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The repair of nervous tissue is a critical research field in tissue engineering because of the degenerative process in the injured nervous system. In this review, we summarize the progress of injectable hydrogels using in vitro and in vivo studies for the regeneration and repair of nervous tissue. Traditional treatments have not been favorable for patients, as they are invasive and inefficient; therefore, injectable hydrogels are promising for the treatment of damaged tissue. This review will contribute to a better understanding of injectable hydrogels as potential scaffolds and drug delivery system for neural tissue engineering applications.

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“…The effects of HA/Gel/SAB/VEGF hydrogel in repair of brain injury was evaluated by a traumatic brain injury model with cavity formation in mice [46]. After 14 and 28 days of hydrogel injection into the brain defects, macroscopic observations of the brain defects were firstly performed, and the images are shown in Figure 7A.…”

Section: Ha/gel/sab/vegf Hydrogel Promotes the Repair Of Brain Injury...mentioning

confidence: 99%

“…A TBI model was established by using 7-to 8-week-old C57BL/6 mice [46]. After anesthesia with isoflurane, the mice were immobilized on a brain stereotaxic device.…”

Section: Establishment Of Tbi Model and Hydrogel Implantationmentioning

confidence: 99%

Injectable Hydrogels Based on Hyaluronic Acid and Gelatin Combined with Salvianolic Acid B and Vascular Endothelial Growth Factor for Treatment of Traumatic Brain Injury in Mice

Zhou,

Cao,

Yan

et al. 2024

Molecules

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Traumatic brain injury (TBI) leads to structural damage in the brain, and is one of the major causes of disability and death in the world. Herein, we developed a composite injectable hydrogel (HA/Gel) composed of hyaluronic acid (HA) and gelatin (Gel), loaded with vascular endothelial growth factor (VEGF) and salvianolic acid B (SAB) for treatment of TBI. The HA/Gel hydrogels were formed by the coupling of phenol-rich tyramine-modified HA (HA-TA) and tyramine-modified Gel (Gel-TA) catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). SEM results showed that HA/Gel hydrogel had a porous structure. Rheological test results showed that the hydrogel possessed appropriate rheological properties, and UV spectrophotometry results showed that the hydrogel exhibited excellent SAB release performance. The results of LIVE/DEAD staining, CCK-8 and Phalloidin/DAPI fluorescence staining showed that the HA/Gel hydrogel possessed good cell biocompatibility. Moreover, the hydrogels loaded with SAB and VEGF (HA/Gel/SAB/VEGF) could effectively promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). In addition, the results of H&E staining, CD31 and α-SMA immunofluorescence staining showed that the HA/Gel/SAB/VEGF hydrogel possessed good in vivo biocompatibility and pro-angiogenic ability. Furthermore, immunohistochemical results showed that the injection of HA/Gel/SAB/VEGF hydrogel to the injury site could effectively reduce the volume of defective tissues in traumatic brain injured mice. Our results suggest that the injection of HA/Gel hydrogel loaded with SAB and VEGF might provide a new approach for therapeutic brain tissue repair after traumatic brain injury.

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Engineering of an electrically charged hydrogel implanted into a traumatic brain injury model for stepwise neuronal tissue reconstruction

Cited by 9 publications

References 56 publications

Neuritogenic glycosaminoglycan hydrogels promote functional recovery after severe traumatic brain injury

Neuritogenic glycosaminoglycan hydrogels promote functional recovery after severe traumatic brain injury

Injectable Hydrogels for Nervous Tissue Repair—A Brief Review

Injectable Hydrogels Based on Hyaluronic Acid and Gelatin Combined with Salvianolic Acid B and Vascular Endothelial Growth Factor for Treatment of Traumatic Brain Injury in Mice

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