C. Le Visage (Nantes, FR)
Regenerative Medicine and Skeleton Inserm U1229 - Université de NantesPresenter Of 1 Presentation
10.4.3 - Design and evaluation of electrospun structured polycaprolactone biomaterials for annulus fibrosus repair
- C. Le Visage (Nantes, FR)
- M. Gluais (Nantes, FR)
- J. Clouet (Nantes, FR)
- M. Fusellier (Nantes, FR)
- C. Decante (Nantes, FR)
- C. Moraru (Nantes, FR)
- M. Dutilleul (Nantes, FR)
- J. Veziers (Nantes, FR)
- J. Lesoeur (Nantes, FR)
- D. Dumas (Vandoeuvre, FR)
- J. Abadie (Nantes, FR)
- A. Hamel (Nantes, FR)
- E. Bord (Nantes, FR)
- S. Chew (Singapore, SG)
- J. Guicheux (Nantes, FR)
Abstract
Purpose
Extensive Annulus fibrosus (AF) radial tears lead to intervertebral disc (IVD) herniation. While unrepaired defects in the AF are associated with high IVD degeneration prevalence, current surgical strategies disregard the structural integrity of the AF. This study aims at i) designing polycaprolactone (PCL) electrospun implants that mimic the AF multi-lamellar fibrous structure and ii) assessing their ability to properly repair an AF defect in a sheep model.
Methods and Materials
Oriented and non-oriented PCL implants were produced by electrospinning. In vitro apposition of ovine annular explants was characterized by cell morphology (nucleus and F-actin staining, EdU proliferation assay) and extracellular matrix (ECM) deposition (collagen, aggrecan). In vivo study was carried out on 6 sheep in which 5 lumbar discs were exposed using a left retroperitoneal approach. Box-shape defects (2x5mm, 2mm depth) were created in the outer AF, with randomized conditions including 10-layer implants, untreated and healthy groups. X-ray and MRI examinations were performed at 1 month, followed by immuno-histological analysis and second harmonic generation microscopy (SHG).
Results
PCL implants with average fiber diameters of 1µm and a tensile modulus (55±1MPa) matching the one of a native human AF lamella (~47MPa) were obtained (Fig. 1). In vitro spontaneous colonization of PCL implants by ovine AF explants was demonstrated at 14 and 28 days. In sheep, successful implantations of PCL implants were achieved. While empty defects exhibited irregular fibrous reparative tissue with numerous vascular ingrowths, cell infiltration between and within the implants, and a continuous type I collagen tissue formation between the implants and the surrounding AF tissue were evidenced (Fig. 2). SHG quantitative analysis confirmed that neo-synthesized collagen fibers were aligned within each layer, replicating the native AF tissue organization.
Conclusion
These results highlight that a cell-free multi-layer PCL electrospun implant is a promising biomaterial for AF repair.