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

Abstract

Background To assess the effects of proteoglycan-depleted regions of annular disruptions on nerve ingrowth in the injury site in vivo. Methods New 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. Results The 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. Conclusion ChABC-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.

Minimally Invasive Intradiscal Delivery of BM-MSCs via Fibrous Microscaffold Carriers

“…Both CH and CS have a water-binding ability. At the same time, CS can alleviate one of the pathophysiologies of discogenic LBP suggested to involve sensitization from the ingrowth of sensory nerve fibers into the IVD . Microscaffolds enabled easy and homogeneous attachment of bone marrow-derived mesenchymal stromal cells (BM-MSC) and could be applied as injectable 3D microcellular niches for site-directed cell delivery.…”