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아주대학교 의과대학

Biomaterials, Volume 284, May 2022, 121526 | https://doi.org/10.1016/j.biomaterials.2022.121526 Dual-functional hydrogel system for spinal cord regeneration with sustained release of arylsulfatase B alleviates fibrotic microenvironment and promotes axonal regeneration.

Hee Hwan Park ^a,b,1, Young-Min Kim ^d,e,1, Le Thi Anh Hong ^a, Hyung Soon Kim ^a,b, Sung Hoon Kim ^d,e, Xuelian Jin ^a,b,f, Dong Hoon Hwang ^a, Min Jung Kwon ^a, Soo-Chang Song ^d,e,**, Byung Gon Kim ^a,b,c,*

^a Department of Brain Science, Ajou University School of Medicine, Suwon, 443-721, Republic of Korea ^b Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 443-721, Republic of Korea ^c Department of Neurology, Ajou University School of Medicine, Suwon, 443-721, Republic of Korea ^d Center for Biomaterials, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea ^e Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, 02792, Republic of Korea ^f Department of Nephrology, Suqian First Hospital, Suqian, 223800, Jiangsu Province, China

^* Corresponding author.
^** Corresponding author.
¹ These two authors contributed equally to this work.

Abstract

Traumatic damage to the spinal cord does not spontaneously heal, often leading to permanent tissue defects. We have shown that injection of imidazole-poly(organophosphazene) hydrogel (I-5) bridges cystic cavities with the newly assembled fibronectin-rich extracellular matrix (ECM). The hydrogel-created ECM contains chondroitin sulfate proteoglycans (CSPGs), collagenous fibrils together with perivascular fibroblasts, and various fibrotic proteins, all of which could hinder axonal growth in the matrix. In an in vitro fibrotic scar model, fibroblasts exhibited enhanced sensitivity to TGF-β1 when grown on CSPGs. To alleviate the fibrotic microenvironment, the I-5 hydrogel was equipped with an additional function by making a complex with ARSB, a human enzyme degrading CSPGs, via hydrophobic interaction. Delivery of the I-5/ARSB complex significantly diminished the fibrotic ECM components. The complex promoted serotonergic axonal growth into the hydrogel-induced matrix and enhanced serotonergic innervation of the lumbar motor neurons. Regeneration of the propriospinal axons deep into the matrix and to the lumbar spinal cord was robustly increased accompanied by improved locomotor recovery. Therefore, our dual-functional system upgraded the functionality of the hydrogel for spinal cord regeneration by creating ECM to bridge tissue defects and concurrently facilitating axonal connections through the newly assembled ECM.

논문정보

형식Research article
게재일2022년 05월 (BRIC 등록일 2022-05-20)
연구진국내(교신)+국외 연구진
분야 의약학 > 신경의학

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