Nanoarchitectonics of tannic acid based injectable hydrogel regulate the microglial phenotype to enhance neuroplasticity for poststroke rehabilitation

Zongjian Liu; Shulei Zhang; Yuanyuan Ran; Huimin Geng; Fuhai Gao; Guiqin Tian; Zengguo Feng; Jianing Xi; Lin Ye; Wei Su

doi:10.1186/s40824-023-00444-0

Nanoarchitectonics of tannic acid based injectable hydrogel regulate the microglial phenotype to enhance neuroplasticity for poststroke rehabilitation

Biomater Res. 2023 Oct 31;27(1):108. doi: 10.1186/s40824-023-00444-0.

Authors

Zongjian Liu^#¹, Shulei Zhang^#², Yuanyuan Ran^#¹, Huimin Geng³, Fuhai Gao¹, Guiqin Tian¹, Zengguo Feng², Jianing Xi¹, Lin Ye⁴, Wei Su⁵

Affiliations

¹ Beijing Rehabilitation Hospital, Capital Medical University, Beijing, 100144, China.
² School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China.
³ Department of Neurosurgery, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012, China. hmgeng@sdu.edu.cn.
⁴ School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, 100081, China. yelin@bit.edu.cn.
⁵ Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China. swa01179@btch.edu.cn.

^# Contributed equally.

Abstract

Background: Stroke is the second leading cause of mortality and disability worldwide. Poststroke rehabilitation is still unsatisfactory in clinics, which brings great pain and economic burdens to stroke patients. In this study, an injectable hydrogel in which tannic acid (TA) acts as not only a building block but also a therapeutic drug, was developed for poststroke rehabilitation.

Methods: TA is used as a building block to form an injectable hydrogel (TA gel) with carboxymethyl chitosan (CMCS) by multivalent hydrogen bonds. The morphology, rheological properties, and TA release behavior of the hydrogel were characterized. The abilities of the TA gel to modulate microglial (BV2 cells) polarization and subsequently enhance the neuroplasticity of neuro cells (N2a cells) were assessed in vitro. The TA gel was injected into the cavity of stroke mice to evaluate motor function recovery, microglial polarization, and neuroplasticity in vivo. The molecular pathway through which TA modulates microglial polarization was also explored both in vitro and in vivo.

Results: The TA gel exhibited sustainable release behavior of TA. The TA gel can suppress the expression of CD16 and IL-1β, and upregulate the expression of CD206 and TGF-β in oxygen and glucose-deprived (OGD) BV2 cells, indicating the regulation of OGD BV2 cells to an anti-inflammatory phenotype in vitro. This finding further shows that the decrease in synaptophysin and PSD95 in OGD N2a cells is effectively recovered by anti-inflammatory BV2 cells. Furthermore, the TA gel decreased CD16/iNOS expression and increased CD206 expression in the peri-infarct area of stroke mice, implying anti-inflammatory polarization of microglia in vivo. The colocalization of PSD95 and Vglut1 stains, as well as Golgi staining, showed the enhancement of neuroplasticity by the TA gel. Spontaneously, the TA gel successfully recovered the motor function of stroke mice. The western blot results in vitro and in vivo suggested that the TA gel regulated microglial polarization via the NF-κB pathway.

Conclusion: The TA gel serves as an effective brain injectable implant to treat stroke and shows promising potential to promote poststroke rehabilitation in the clinic.

Keywords: Anti-inflammatory phenotype; Injectable hydrogel; Microglia; Stroke; Tannic acid.

Abstract

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