이정환 (단국대학교 조직재생공학연구원/치과대학/나노바이오의과학과) | 한빛사논문 > 한빛사

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단국대학교 조직재생공학연구원/치과대학/나노바이오의과학과

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Adv. Healthc. Mater., First published: 29 November 2022 | https://doi.org/10.1002/adhm.202201720 Delivery of Induced Neural Stem Cells Through Mechano-Tuned Silk–Collagen Hydrogels for the Recovery of Contused Spinal Cord in Rats

Ganchimeg Davaa^1,2,#, Jin-Young Hong^1,2,#, Jung-Hwan Lee^{1,2,3,4,11,12,#}, Min Soo Kim^1,2, Jennifer O. Buitrago^1,2,5, Yu Meng Li^1,2, Hae-Hyoung Lee^1,2,3,4, Dong Wook Han⁶, Kam W. Leong^2,7,8, Jung Keun Hyun^1,2,9,10,*, Hae-Won Kim^{1,2,3,4,11,12,*}

¹Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Republic of Korea
²Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Republic of Korea
³Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 31116, Republic of Korea
⁴Cell& Matter Institute, Dankook University, Cheonan 31116, Republic of Korea
⁵Departament de Ciències Bàsiques, Departament de Ciències Bàsiques. Universitat Internacional de Catalunya, Barcelona, Spain
⁶Konkuk University Open-Innovation Center, Institute of Biomedical Science & Technology, Konkuk University, Seoul 143701, Republic of Korea
⁷Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
⁸Department of Systems Biology, Columbia University Medical Center, New York, NY, 10032, USA
⁹Department of Rehabilitation Medicine, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea
¹⁰Wiregene Co., Ltd., Cheonan 31116, Republic of Korea
¹¹UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan31116, Republic of Korea
¹²Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan 31116, Republic of Korea

^#G. Davaa, J. Hong, and J. Lee contributed equally to this work.
^*Corresponding authors: Jung Keun Hyun, Hae-Won Kim

Abstract

Neural stem cells (NSC) have tremendous potential for therapeutic regeneration of diseased or traumatized neural tissues, including injured spinal cord. However, transplanted NSC suffer from low cell survival and uncontrolled differentiation, limiting in vivo efficacy. Here we tackle this issue by delivery through silk-collagen protein hydrogels that are stiffness-matched, stress-relaxing and shear-thinning. The mechanically-tuned hydrogels protected NSC reprogrammed from fibroblasts initially from injection shear-stress, and enhanced long-term survival over 12 weeks. Hydrogel-NSC treatment alleviated neural inflammation, with reduced inflammatory cells and lesions than NSC-only. The NSC migrated from the hydrogel into surrounding tissues, secreted up-regulated neurotrophic factors, and differentiated into neural cell subtypes, forming synapses. More serotonergic axons were observed in the lesion cavity, and locomotor functions were improved in hydrogel-NSC than in NSC-only. This study highlights the ability of mechanically-tuned protein hydrogels to protect NSC from the injection stress and severe inflammatory environment, allowing them to differentiate and function to recover injured spinal cord. This article is protected by copyright. All rights reserved.

논문정보

형식Research article
게재일2022년 11월 (BRIC 등록일 2022-12-05)
연구진국내(교신)+국외 연구진
분야 의약학 > 재생의학

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