Hyaluronic Acid Microgels Modulate Inflammation and Key Matrix Molecules toward a Regenerative Signature in the Injured Annulus Fibrosus

Low back pain results from disc degeneration, which is a chronic inflammatory disease characterized by an imbalance between anabolic and catabolic factors. Today, regenerative medicine is focused on identifying inflammatory markers to target disc disease. Hyaluronan is used as a scaffold for cell de...

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Bibliographic Details
Published in:Advanced biosystems 2017-10, Vol.1 (10), p.e1700077-n/a
Main Authors: Kazezian, Zepur, Sakai, Daisuke, Pandit, Abhay
Format: Article
Language:English
Subjects:
annulus fibrosus
disc repair
hyaluronic acid
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Summary:Low back pain results from disc degeneration, which is a chronic inflammatory disease characterized by an imbalance between anabolic and catabolic factors. Today, regenerative medicine is focused on identifying inflammatory markers to target disc disease. Hyaluronan is used as a scaffold for cell delivery in disc degeneration; however, to date high molecular weight hyaluronan (HMW HA) is evaluated for its anti‐inflammatory and matrix modulatory properties in an in vivo disc injury model. Ex vivo bovine organ culture studies demonstrate the anti‐inflammatory and matrix modulatory effects of HMW HA on the IFNα2β signaling pathway that provides the motivation for evaluating its efficacy in regenerating the annulus fibrosus in an in vivo disc injury model. It is demonstrated that the HMW HA microgel acts as an anti‐inflammatory molecule in the annulus fibrosus, by downregulating the expression of the pro‐inflammatory interferon gamma (IFNα) and pro‐apoptotic insulin‐like growth factor‐binding protein 3 (IGFBP3) and the apoptosis marker caspase 3. Mass spectrometry studies demonstrate that the HMW HA microgel modulates the matrix modulatory effect by upregulating hyaluronic acid link protein (HAPLN1) and aggrecan, which are further confirmed by immunostaining. The microgel's regenerative capacity is illustrated by the increase in the disc height index. This study validates the anti‐inflammatory and matrix modulatory effects of a high molecular weight hyaluronan (HMWHA) microgel in intervertebral discs. HMWHA down‐regulates the pro‐inflammatory and pro‐apoptotic factors while up‐regulating the extracellular matrix in the annulus fibrosus inducing an increase in the disc height. This microgel thus has a therapeutic application in intervertebral disc repair.
ISSN:2366-7478
2366-7478
DOI:10.1002/adbi.201700077