Efficacy of HYADD®4-G single intra-discal injections in a rabbit model of intervertebral disc degeneration

Biomed Mater Eng. 2019;30(4):403-417. doi: 10.3233/BME-191062.

Abstract

Background: Various biomaterials/technologies have been tested for treatment of intervertebral disc (IVD) degeneration (IDD). Only few non-surgical options exist.

Objective: Assessment of efficacy and safety of the hyaluronic acid derivative hydrogel HYADD®4-G in IDD using a well-established rabbit annular puncture model.

Methods: Rabbits were punctured at two IVDs to induce IDD. Thirty days after, IVDs were injected with HYADD®4-G or saline. IVD hydration, height, appearance and tissue organization were assessed by radiographs, MRI and histopathology. Safety of HYADD®4-G injection was evaluated in non-punctured IVDs.

Results: HYADD®4-G injection restored disc height to over 75% of the pre-punctured disc, saline injections led to 50% of initial disc height. Compared to saline, HYADD®4-G treatment resulted in improved water retention as revealed by MRI quantification. 83.3% of HYADD®4-G injected discs had normal appearance and reached grade I of the Pfirrmann scale. Regarding tissue organization and cellularity, HYADD®4-G treatment resulted in significantly lower IDD scores than saline (p < 0.01). HYADD®4-G injected into healthy IVDs did not induce inflammation or foreign body reactions.

Conclusions: Intra-discal HYADD®4-G injection is safe and has therapeutic benefits: IDD could be limited through restoration of disc height and hydration and maintenance of normal IVD tissue organization.

Keywords: HYADD®4-G; Intervertebral disc degeneration; annulus fibrosus (AF); annulus puncture rabbit model; disc therapy; nucleus pulposus (NP).

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / therapeutic use*
  • Hydrogels / administration & dosage
  • Hydrogels / therapeutic use*
  • Injections, Spinal
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / pathology*
  • Intervertebral Disc Degeneration / pathology
  • Intervertebral Disc Degeneration / therapy*
  • Rabbits
  • Viscosupplements / administration & dosage
  • Viscosupplements / therapeutic use*

Substances

  • HYADD 4
  • Hydrogels
  • Viscosupplements
  • Hyaluronic Acid