title: Positively Charged Oligo[Poly(Ethylene Glycol) Fumarate] Scaffold Implantation Results in a Permissive Lesion Environment after Spinal Cord Injury in Rat.
abstract: Positively charged oligo[poly(ethylene glycol) fumarate] (OPF+) scaffolds loaded with Schwann cells bridge spinal cord injury (SCI) lesions and support axonal regeneration in rat. The regeneration achieved is not sufficient for inducing functional recovery. Attempts to increase regeneration would benefit from understanding the effects of the scaffold and transplanted cells on lesion environment. We conducted morphometric and stereological analysis of lesions in rats implanted with OPF+ scaffolds with or without loaded Schwann cells 1, 2, 3, 4, and 8 weeks after thoracic spinal cord transection. No differences were found in collagen scarring, cyst formation, astrocyte reactivity, myelin debris, or chondroitin sulfate proteoglycan (CSPG) accumulation. However, when scaffold-implanted animals were compared with animals with transection injuries only, these barriers to regeneration were significantly reduced, accompanied by increased activated macrophages/microglia. This distinctive and regeneration permissive tissue reaction to scaffold implantation was independent of Schwann cell transplantation. Although the tissue reaction was beneficial in the short term, we observed a chronic fibrotic host response, resulting in scaffolds surrounded by collagen at 8 weeks. This study demonstrates that an appropriate biomaterial scaffold improves the environment for regeneration. Future targeting of the host fibrotic response may allow increased axonal regeneration and functional recovery.
authors.affiliation: 1 Mayo Clinic College of Medicine , Mayo Clinic, Rochester, Minnesota.|2 Mayo Graduate School , Mayo Clinic, Rochester, Minnesota.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Hakim
authors.affiliation: 2 Mayo Graduate School , Mayo Clinic, Rochester, Minnesota.
authors.forename: Melika
authors.initials: M
authors.lastname: Esmaeili Rad
authors.affiliation: 2 Mayo Graduate School , Mayo Clinic, Rochester, Minnesota.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grahn
authors.affiliation: 3 Department of Neurology, Mayo Clinic , Rochester, Minnesota.
authors.forename: Bingkun K
authors.initials: BK
authors.lastname: Chen
authors.affiliation: 3 Department of Neurology, Mayo Clinic , Rochester, Minnesota.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Knight
authors.affiliation: 3 Department of Neurology, Mayo Clinic , Rochester, Minnesota.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Schmeichel
authors.affiliation: 2 Mayo Graduate School , Mayo Clinic, Rochester, Minnesota.
authors.forename: Nasro A
authors.initials: NA
authors.lastname: Isaq
authors.affiliation: 1 Mayo Clinic College of Medicine , Mayo Clinic, Rochester, Minnesota.|4 Department of Orthopedic Surgery, Mayo Clinic , Rochester, Minnesota.
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.affiliation: 1 Mayo Clinic College of Medicine , Mayo Clinic, Rochester, Minnesota.|4 Department of Orthopedic Surgery, Mayo Clinic , Rochester, Minnesota.|5 Center for Regenerative Medicine , Mayo Clinic, Rochester, Minnesota.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.affiliation: 1 Mayo Clinic College of Medicine , Mayo Clinic, Rochester, Minnesota.|3 Department of Neurology, Mayo Clinic , Rochester, Minnesota.|5 Center for Regenerative Medicine , Mayo Clinic, Rochester, Minnesota.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Windebank
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D005260:Female; D005650:Fumarates / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology*; D019919:Prosthesis Implantation; D011509:Proteoglycans / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000628:therapy*; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D005650:Fumarates; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; D011509:Proteoglycans; C508734:poly(ethylene glycol fumarate); D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols