Effects of annulus defects and implantation of polylactic-co-glycolic acid PLGA-fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular injury disc degenerationReport as inadecuate

Effects of annulus defects and implantation of polylactic-co-glycolic acid PLGA-fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular injury disc degeneration - Download this document for free, or read online. Document in PDF available to download.

Journal of Orthopaedic Surgery and Research

, 12:73

First Online: 12 May 2017Received: 13 November 2016Accepted: 26 April 2017DOI: 10.1186-s13018-017-0572-5

Cite this article as: Xin, L., Xu, W., Yu, L. et al. J Orthop Surg Res 2017 12: 73. doi:10.1186-s13018-017-0572-5


BackgroundGrowth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration IVD induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with polylactic-co-glycolic acid-fibrin gel PLGA plugs.

MethodsNew Zealand white rabbits n = 24 received annular injuries at three lumbar levels L3-4, L4-5, and L5-6. The discs were randomly assigned to four groups: a annular defect 1.8-mm diameter; 4-mm depth by mini-trephine, b annular defect implanted with a PLGA scaffold containing a fibrin gel, c annular puncture by a 16G needle 5-mm depth, and d uninjured L2-3 disc control. Disc degeneration was evaluated by radiography, MRI, histology, real-time PCR, and analysis of proteoglycan PG content. Nerve ingrowth into the discs was assessed by immunostaining with the nerve marker protein gene product 9.5.

ResultsInjured discs showed a progressive disc space narrowing with significant disc degeneration and proteoglycan loss, as confirmed by imaging results, molecular and compositional analysis, and histological examinations. In 16G punctured discs, nerve ingrowth was observed on the surface of scar tissue. In annular defects, nerve fibers were found to be distributed along small fissures within the fibrocartilaginous-like tissue that filled the AF. In discs filled with PLGA- fibrin gel, more nerve fibers were observed growing deeper into the inner AF along the open annular track.  In addition, innervations scores showed significantly higher than those of punctured discs and empty defects. A limited vascular proliferation was found in the injured sites and regenerated tissues.

ConclusionsNerve ingrowth was significantly higher in PLGA-fibrin-filled discs than in empty defects. Possible explanations include i annular fissures along the defect and early loss of proteoglycan may facilitate the ingrowth process and ii biodegradable PLGA-fibrin gel may promote adverse growth of nerves and blood vessels into deeper parts of injured disc. The rabbit annular defect model of disc degeneration appears suitable to investigate the effects of nerve ingrowth in relation to pain generation.

KeywordsPLGA scaffold Fibrin gel Proteoglycan Nerve ingrowth Blood vessels Annular injury model AbbreviationsAFAnnulus fibrosus

ANOVAAnalysis of Variance

DHIDisc height index

DMMB1,9-Dimethylmethylene blue

EDTAEthylenediamine tetraacetic acid


GAPDHGlyceraldehyde-3-phosphate dehydrogenase


HRPHorseradish peroxidase

IVDIntravertebral disc degeneration

LSDLeast Significant Difference

MRIMagnetic resonance imaging

NPNucleus pulposus

PACSPicture archiving and communication system

PCRPolymerase chain reaction

PLGAPolylactic-co-glycolic acid

Author: Long Xin - Weixing Xu - Leijun Yu - Shunwu Fan - Wei Wang - Fang Yu - Zhenbin Wang

Source: https://link.springer.com/

Related documents