Minimal invasive annulotomy for induction of disc degeneration and implantation of poly (lactic-co-glycolic acid) (PLGA) plugs for annular repair in a rabbit model

Eur J Med Res. 2016 Feb 29:21:7. doi: 10.1186/s40001-016-0202-4.

Abstract

Background: The rabbit disc model is useful for the study of intervertebral disc (IVD) degeneration and experimental therapeutic interventions. The annulotomy-induced disc models present several drawbacks, particularly an excessive disruption of disc integrity and a rapidly disc degeneration; therefore, this study sought to establish a minimal invasive annulotomy for induction of disc degeneration model, combined to annulus repair using implantation of a PLGA (poly lactic-co-glycolic acid) plug.

Methods: New Zealand white rabbits (n = 24) received annular injuries in three discs (L3/4, L4/5 and L5/6). The experimental discs were randomly assigned to four groups: (a) annular defect with a 1.8 mm diameter mini-trephine; (b) annular puncture by 16G needle; (c) annular defect with a PLGA plug implanted by press-fit fashion; (d) uninjured L2/3 disc served as control. Postsurgical x-ray, MRI examination, and real-time PCR analysis were performed at 1, 3 and 6 months. Gross morphology and histology were evaluated at postoperative 6 months.

Results: Radiographic examinations showed a slow, progressive disc space narrowing and a significant degree of disc degeneration on MRI grade in the injured discs at 6 months in all rabbits. Histological examinations and aggrecan, Col1A1, Col2A1 and matrix metalloprotease (MMP)-3 mRNA expression confirmed the disc degeneration, supporting the imaging results. The PLGA implantation reduced the marked loss of T2-weighted signal intensity seen at MRI in the injured discs and slowly decreased the disc height index (DHI) over the follow-up period. HE/Safranin O staining showed that annular defect was replaced by regenerated connective tissue with significant loss of proteoglycan content.

Conclusions: The minimally invasive approach for the creation of annular defects by an appropriately sized mini-Trephine is a suitable option for the study of disc degeneration in a rabbit model. Implantation of a suitable PLGA plug induced a successful repair of the annulus fibrosus within the degenerated disc, and retarded the degenerative process in the annular injury model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggrecans / genetics
  • Animals
  • Biocompatible Materials / pharmacology
  • Collagen Type I / genetics
  • Collagen Type II / genetics
  • Disease Models, Animal
  • Diskectomy / adverse effects
  • Diskectomy / instrumentation
  • Diskectomy / methods
  • Gene Expression / drug effects
  • Humans
  • Implants, Experimental
  • Intervertebral Disc / drug effects*
  • Intervertebral Disc / injuries
  • Intervertebral Disc / metabolism
  • Intervertebral Disc Degeneration / diagnostic imaging
  • Intervertebral Disc Degeneration / drug therapy*
  • Intervertebral Disc Degeneration / etiology
  • Lactic Acid / pharmacology*
  • Magnetic Resonance Imaging
  • Matrix Metalloproteinase 3 / genetics
  • Minimally Invasive Surgical Procedures / adverse effects
  • Minimally Invasive Surgical Procedures / instrumentation
  • Minimally Invasive Surgical Procedures / methods
  • Polyglycolic Acid / pharmacology*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rabbits
  • Radiography
  • Random Allocation
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Aggrecans
  • Biocompatible Materials
  • Collagen Type I
  • Collagen Type II
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Matrix Metalloproteinase 3