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Nat. Commun., 8, Article number: 533 (2017) | doi:10.1038/s41467-017-00583-8
An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling
Le Thi Anh Hong1,2, Young-Min Kim3, Hee Hwan Park1,2, Dong Hoon Hwang1, Yuexian Cui1,2, Eun Mi Lee1, Stephanie Yahn4, Jae K. Lee4, Soo-Chang Song3,5,* & Byung Gon Kim1,2,6,*
1Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea. 2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea.3 Center for Biomaterials, Korea Institute of Science and Technology (KIST), 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.4 Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, 1095 NW 14th Terrace (R-48), Miami, FL 33136, USA. 5Department of Biomolecular Science, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Republic of Korea.6Department of Neurology, Ajou University School of Medicine, 164, Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea. Le Thi Anh Hong, Young-Min Kim and Hee Hwan Park contributed equally to this work.
1Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea. 2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea.3 Center for Biomaterials, Korea Institute of Science and Technology (KIST), 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.4 Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, 1095 NW 14th Terrace (R-48), Miami, FL 33136, USA. 5Department of Biomolecular Science, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Republic of Korea.6Department of Neurology, Ajou University School of Medicine, 164, Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea. Le Thi Anh Hong, Young-Min Kim and Hee Hwan Park contributed equally to this work.
*Correspondence to Soo-Chang Song or Byung Gon Kim
Abstract
The cystic cavity that develops following injuries to brain or spinal cord is a major obstacle for tissue repair in central nervous system (CNS). Here we report that injection of imidazole-poly(organophosphazenes) (I-5), a hydrogel with thermosensitive sol?gel transition behavior, almost completely eliminates cystic cavities in a clinically relevant rat spinal cord injury model. Cystic cavities are bridged by fibronectin-rich extracellular matrix. The fibrotic extracellular matrix remodeling is mediated by matrix metalloproteinase-9 expressed in macrophages within the fibrotic extracellular matrix. A poly(organophosphazenes) hydrogel lacking the imidazole moiety, which physically interacts with macrophages via histamine receptors, exhibits substantially diminished bridging effects. I-5 injection improves coordinated locomotion, and this functional recovery is accompanied by preservation of myelinated white matter and motor neurons and an increase in axonal reinnervation of the lumbar motor neurons. Our study demonstrates that dynamic interactions between inflammatory cells and injectable biomaterials can induce beneficial extracellular matrix remodeling to stimulate tissue repair following CNS injuries.
논문정보
- Research article
- 2017년 09월 (BRIC 등록일 2017-09-20)
- 국내(교신)+국외 연구진
- 의약학 > 신경의학
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