Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

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 m...

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Published in:Journal of biomedical materials research. Part B, Applied biomaterials Applied biomaterials, 2017-05, Vol.105 (4), p.707-714
Main Authors: Willems, Nicole, Mihov, George, Grinwis, Guy C M, van Dijk, Maarten, Schumann, Detlef, Bos, Clemens, Strijkers, Gustav J, Dhert, Wouter J A, Meij, Björn P, Creemers, Laura B, Tryfonidou, Marianna A
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - drug effects
bcl-2-Associated X Protein - biosynthesis
Biocompatibility
Biomaterials
Biomedical materials
Calcium channels (voltage-gated)
Controlled release
Cytotoxicity
Degeneration
Disease Models, Animal
Dogs
Drug Evaluation, Preclinical
Gene Expression Regulation - drug effects
Histopathology
Hypodermic needles
Immunohistochemistry
Implantation
Injection
Intervertebral Disc Degeneration - metabolism
Intervertebral Disc Degeneration - pathology
Intervertebral Disc Degeneration - therapy
Intervertebral discs
Materials research
Materials science
Materials Testing
Mice
Microscopy
Microspheres
Needles
Original Research Report
Original Research Reports
Peas
Polyesters
Polyesters - adverse effects
Polyesters - pharmacology
Polymers
Rabbits
Senescence
Surgical implants
Sustained release
Toxicity
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Summary: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.
ISSN:1552-4973
1552-4981
DOI:10.1002/jbm.b.33579