title: Peptide-Tethered Hydrogel Scaffold Promotes Recovery from Spinal Cord Transection via Synergism with Mesenchymal Stem Cells.
abstract: Spinal cord injury (SCI) is one of the most devastating injuries. Treatment strategies for SCI are required to overcome comprehensive issues. Implantation of biomaterial scaffolds and stem cells has been demonstrated to be a promising strategy. However, a comprehensive recovery effect is difficult to achieve. In the comprehensive treatment process, the specific roles of the implanted scaffolds and of stem cells in combined strategy are usually neglected. In this study, a peptide-modified scaffold is developed based on hyaluronic acid and an adhesive peptide PPFLMLLKGSTR. Synchrotron radiation micro computed tomography measurement provides insights to the three-dimensional inner topographical property and perspective porous structure of the scaffold. The modified scaffold significantly improves cellular survival and adhesive growth of mesenchymal stem cells during 3D culture in vitro. After implantation in transected spinal cord, the modified scaffold and mesenchymal stems are found to function in synergy to restore injured spinal cord tissue, with respective strengths. Hindlimb motor function scores exhibit the most significant impact of the composite implant at 2 weeks post injury, which is the time secondary injury factors begin to take hold. Investigation on the secondary injury factors including inflammatory response and astrocyte overactivity at 10 days post injury reveals the possible underlying reason. Implants of the scaffold, cells, and especially the combination of both elicit inhibitory effects on these adverse factors. The study develops a promising implant for spinal cord tissue engineering and reveals the roles of the scaffold and stem cells. More importantly, the results provide the first understanding of the bioactive peptide PPFLMLLKGSTR concerning its functions on mesenchymal stem cells and spinal cord tissue restoration.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.forename: Xin-Chi
authors.initials: XC
authors.lastname: Jiang
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201210, China.
authors.forename: Xian-Zhen
authors.initials: XZ
authors.lastname: Yin
authors.forename: Fu
authors.initials: F
authors.lastname: Chen
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Ren
authors.affiliation: Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201210, China.
authors.forename: Ji-Wen
authors.initials: JW
authors.lastname: Zhang
authors.forename: Ting-Jun
authors.initials: TJ
authors.lastname: Hou
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Ou-Yang
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University , Kyoto 606-8507, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University , Hangzhou 310027, China.
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Shen
authors.forename: Jian-Qing
authors.identifier: http://orcid.org/0000-0003-1052-7060
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D020100:Hydrogels; D059630:Mesenchymal Stem Cells; D010455:Peptides; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography
chemical_list: D020100:Hydrogels; D010455:Peptides
keywords: adhesive peptide; hyaluronic acid; hydrogel scaffold; mesenchymal stem cells; spinal cord injury; tissue engineering