title: Photochemically crosslinked collagen annulus plug: a potential solution solving the leakage problem of cell-based therapies for disc degeneration.
abstract: Intra-disc injection of mesenchymal stem cells (MSCs) to treat disc degeneration may lead to unfavorable complications, particularly osteophyte formation. Development of an effective method to block the injection portal, prevent the leakage of injected cells and materials and, hence, prevent osteophyte formation is of the utmost importance before MSC-based therapies can be applied in a clinical setting. Here we seek to alleviate the cell leakage problem and the associated complication osteophyte formation by developing an injectable annulus plug to block the injection portal during intra-disc delivery. Specifically, we fabricated a needle-shaped collagen plug by photochemical crosslinking and successfully delivered it intra-discally, in association with MSCs in collagen microsphere carriers, using a custom-made delivery device. The mechanical performance of the plug and its effectiveness in reducing cell leakage were evaluated ex vivo under compression and in torsion push-out tests. The results demonstrate that the plug survived physiologically relevant loadings and significantly reduced leakage and enhanced retention of the injected materials. Finally, a pilot in vivo study in rabbits was conducted to evaluate the performance of the plug. Microcomputed tomography imaging and histology revealed that the plug significantly reduced osteophyte formation. This work suggests the potential of the annulus plug as an adjunct or annulus closure device for intra-disc delivery of cells and materials.
authors.affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region.
authors.forename: T K
authors.initials: TK
authors.lastname: Chik
authors.forename: X Y
authors.initials: XY
authors.lastname: Ma
authors.forename: T H
authors.initials: TH
authors.lastname: Choy
authors.forename: Y Y
authors.initials: YY
authors.lastname: Li
authors.forename: H J
authors.initials: HJ
authors.lastname: Diao
authors.forename: W K
authors.initials: WK
authors.lastname: Teng
authors.forename: S J
authors.initials: SJ
authors.lastname: Han
authors.forename: K M C
authors.initials: KM
authors.lastname: Cheung
authors.forename: B P
authors.initials: BP
authors.lastname: Chan
mesh_terms: D000818:Animals; D003094:Collagen / Q000008:administration & dosage* / Q000528:radiation effects; D003432:Cross-Linking Reagents / Q000528:radiation effects; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000209:etiology* / Q000517:prevention & control*; D005240:Feasibility Studies; D055959:Intervertebral Disc Degeneration / Q000150:complications / Q000601:surgery*; D008027:Light; D008422:Materials Testing; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D010777:Photochemistry / Q000379:methods; D011817:Rabbits
chemical_list: D003432:Cross-Linking Reagents; D003094:Collagen
keywords: Annulus plug; Cell leakage; Intra-disc injection; Osteophyte formation; Photochemical crosslinking