title: Collagen/heparin sulfate scaffolds fabricated by a 3D bioprinter improved mechanical properties and neurological function after spinal cord injury in rats.
abstract: Effective treatments promoting axonal regeneration and functional recovery for spinal cord injury (SCI) are still in the early stages of development. Most approaches have been focused on providing supportive substrates for guiding neurons and overcoming the physical and chemical barriers to healing that arise after SCI. Although collagen has become a promising natural substrate with good compatibility, its low mechanical properties restrict its potential applications. The mechanical properties mainly rely on the composition and pore structure of scaffolds. For the composition of a scaffold, we used heparin sulfate to react with collagen by crosslinking. For the structure, we adopted a three-dimensional (3D) printing technology to fabricate a scaffold with a uniform pore distributions. We observed that the internal structure of the scaffold printed with a 3D bioprinter was regular and porous. We also found that both the compression modulus and strengths of the scaffold were significantly enhanced by the collagen/heparin sulfate composition compared to a collagen scaffold. Meanwhile, the collagen/heparin sulfate scaffold presented good biocompatibility when it was co-cultured with neural stem cells in vitro. We also demonstrated that heparin sulfate modification significantly improved bFGF immobilization and absorption to the collagen by examining the release kinetics of bFGF from scaffolds. Two months after implantating the scaffold into transection lesions in T10 of the spinal cord in rats, the collagen/heparin sulfate group demonstrated significant recovery of locomotor function and according to electrophysiological examinations. Parallel to functional recovery, collagen/heparin sulfate treatment further ameliorated the pathological process and markedly increased the number of neurofilament (NF) positive cells compared to collagen treatment alone. These data suggested that a collagen/heparin sulfate scaffold fabricated by a 3D bioprinter could enhance the mechanical properties of collagen and provide continuous guidance channels for axons, which would improve the neurological function after SCI. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1324-1332, 2017.
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Zhao
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Ren-Kun
authors.initials: RK
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.|Department of Radiology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: Zhao
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Fu
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Sun
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Institute of Traumatic Brain Injury and Neurology, Pingjin Hospital, Logistics University of Chinese People's Armed Police Forces, Tianjin, 300162, China.|Key Laboratory of Neurotrauma Repair of Tianjin, Tianjin, 300162, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
mesh_terms: D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000628:therapy*; D058630:Spinal Cord Regeneration / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D006493:Heparin; D003094:Collagen
keywords: 3D bioprinter; collagen; heparin sulfate; mechanical properties; spinal cord injury