title: Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration.
abstract: Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine model predisposed to IVD degeneration at long-term (6 months) follow-up. PEA extracts did not induce cytotoxicity in mouse fibroblast cells (microscopy and XTT assay), while a slight foreign body reaction was demonstrated by histopathology after intramuscular implantation in rabbits. Intradiscal injection of a volume of 40 µL through 26 and 27G needles induced no degenerative changes in acanine model susceptible to IVD disease. Although sham-injected IVDs showed increased CAV1 expression compared with noninjected IVDs, which may indicate increased cell senescence, these findings were not supported by immunohistochemistry, biomolecular analysis of genes related to apoptosis, biochemical and histopathological results. PEAM-injected IVDs showed significantly higher BAX/BCL2 ratio vs sham-injected IVDs suggestive of an anti-apoptotic effect of the PEAMs. These findings were not supported by other analyses (clinical signs, disc height index, T2 values, biomolecular and biochemical analyses, and IVD histopathology). PEAs showed a good cytocompatibility and biocompatibility. PEAMs are considered safe sustained release systems for intradiscal delivery of biological treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 707-714, 2017.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584, CM, Utrecht, The Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Willems
authors.affiliation: R&D Orthopedics, DSM Biomedical materials B.V., 6167, RA, Geleen, The Netherlands.
authors.forename: George
authors.initials: G
authors.lastname: Mihov
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, 3508 TD Utrecht, The Netherlands.
authors.forename: Guy C M
authors.initials: GC
authors.lastname: Grinwis
authors.affiliation: R&D Orthopedics, DSM Biomedical materials B.V., 6167, RA, Geleen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van Dijk
authors.affiliation: R&D Orthopedics, DSM Biomedical materials B.V., 6167, RA, Geleen, The Netherlands.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schumann
authors.affiliation: Imaging Division, University Medical Center, 3584, CX, Utrecht, The Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: Bos
authors.affiliation: Biomedical Engineering and Physics, Academic Medical Center (AMC), 1100, DE, Amsterdam, The Netherlands.
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584, CM, Utrecht, The Netherlands.|Department of Orthopaedics, University Medical Center, 3584, CX, Utrecht, The Netherlands.
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584, CM, Utrecht, The Netherlands.
authors.forename: Björn P
authors.initials: BP
authors.lastname: Meij
authors.affiliation: Department of Orthopaedics, University Medical Center, 3584, CX, Utrecht, The Netherlands.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, 3584, CM, Utrecht, The Netherlands.
authors.forename: Marianna A
authors.initials: MA
authors.lastname: Tryfonidou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008422:Materials Testing; D051379:Mice; D008863:Microspheres; D011091:Polyesters / Q000009:adverse effects / Q000494:pharmacology*; D011817:Rabbits; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D011091:Polyesters; D051028:bcl-2-Associated X Protein
keywords: biomaterial; dog; intradiscal delivery; microspheres; nucleus pulposus