Proteoglycan-depleted regions of annular injury promote nerve ingrowth in a rabbit disc degeneration model.

Long Xin,Jian Wang,Fang Yu,Shunwu Fan,Xinwei Xu,Weixin Xu,Yang Yang

doi:10.1515/med-2021-0363

Abstract

BackgroundTo assess the effects of proteoglycan-depleted regions of annular disruptions on nerve ingrowth in the injury site in vivo.MethodsNew Zealand white rabbits (n = 18) received annular injuries at L3/4, L4/5, and L5/6. The experimental discs were randomly assigned to four groups: (a) an annular defect was created; (b) an annular defect implanted with a poly lactic-co-glycolic acid (PLGA)/fibrin/PBS plug; (c) an annular defect implanted with a PLGA/fibrin/chondroitinase ABC (chABC) plug; and (d) an uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, and analysis of the proteoglycan (PG) content. Immunohistochemical detection of nerve fibers and chondroitin sulfate (CS) was performed.ResultsThe injured discs produced progressive and reliable disc degeneration. In the defective discs, the lamellated appearance of AF (Annulus fibrosus) was replaced by extensive fibrocartilaginous-like tissue formation outside the injured sites. In contrast, newly formed tissue was distributed along small fissures, and small blood vessels appeared in the outer part of the disrupted area in the PLGA/fibrin/PBS discs. More sprouting nerve fibers grew further into the depleted annulus regions in the PLGA/fibrin/chABC discs than in the control discs and those receiving PLGA/fibrin/PBS. In addition, the innervation scores of the PLGA/fibrin/chABC discs were significantly increased compared with those of the PLGA/fibrin/PBS discs and defected discs.ConclusionChABC-based PLGA/fibrin gel showed promising results by achieving biointegration with native annulus tissue and providing a local source for the sustained release of active chABC. Disc-derived PG-mediated inhibition of nerve and blood vessel ingrowth was abrogated by chABC enzymatic deglycosylation in an annular-injured rabbit disc degeneration model.

Highlights

IntroductionThe pathophysiology of this condition remains uncertain, degeneration of the intervertebral disc (IVD) is believed to be a major cause of low back pain [1,2,3]
Low back pain is an extremely common socioeconomic problem in orthopedics
Fabricated poly lactic-co-glycolic acid (PLGA) sponges filled with fibrin gel and the chondroitinase ABC (chABC) coating of the PLGA/fibrin construct were assessed by SEM and are shown in Figure 1a and b, respectively

Summary

Introduction

The pathophysiology of this condition remains uncertain, degeneration of the intervertebral disc (IVD) is believed to be a major cause of low back pain [1,2,3]. This degenerative change results in increased matrix degradation, proinflammatory cytokine expression, and inferior mechanical properties [4,5,6]. It has been shown that aggrecan, a proteoglycan (PG) found in the disc, may act as a barrier to inhibit nerve fiber growth in vivo and in vitro [13,14,15,16]. We established a minimally invasive annulotomy-induced rabbit model and demonstrated the growth of orientated growth-permissive nerves into

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