A degradable nanofibrous scaffold of poly(ε-Caprolactone-co-Lactide) for annulus fibrosus repair
The intervertebral disc (IVD) is a key contributor to the spines biomechanical functions. It consists of a gelatinous core (nucleus pulposus, NP) surrounded by a fibrous ring (annulus fibrosus, AF). Accumulation of microcracks and tears in the AF can lead to NP herniation outside the disc space, compressing the nerve roots and causing pain. Herniation is a leading cause of low back pain and represents a major socioeconomic burden, with no effective regenerative treatment currently available. Previously, we demonstrated the potential of a poly({varepsilon}-caprolactone) (PCL)-based implant for the closure of an annulus fibrosus (AF) defect. However, the slow in vivo degradation of PCL may hinder timely AF regeneration. Here, we hypothesized that accelerating PCL degradation kinetics by incorporating a lactide component, known for its rapid degradation, could enhance AF repair. To that aim, PCLA polymers of {varepsilon}-caprolactone and lactide were synthesised as a copolymer (C-CL90%LA10%) or a blend (B-PCL80%PLA20%). These polymers were electrospun into aligned nanofibrous sheets, which were then assembled into a biomimetic multi-lamellar 3D implant. Cytocompatibility was assessed in vitro using ovine AF cells and ex vivo using a bovine tail disc model. In vitro, PCLA sheets promoted ovine AF cell alignment, proliferation, and expression of type I and II collagen. Ex vivo, the multi-lamellar implant remained in place within a full-thickness (4 mm) annular defect in bovine tail discs for 4 weeks, with initial cell infiltration. Degradation and regenerative potential were then evaluated in an ovine lumbar full-thickness annular defect model at 1 month (n=4) and 6 months (n=10) after implantation. Histological and immunohistochemical analyses revealed substantial cellular infiltration and neo-tissue ingrowth within implant layers, despite implant displacement in some cases. At 1 month, all implants retained their multi-lamellar structure with no visible degradation. By 6 months, the copolymer implants exhibited marked degradation, whereas PCL and blend implants remained structurally intact. Furthermore, ex vivo biomechanical testing revealed comparable flexibility to intact but much lower than non-implanted controls in axial rotation. This study confirms the accelerated degradation kinetics of PCLA copolymers within the disc microenvironment and demonstrates that the multi-lamellar PCLA implant can guide AF tissue repair. Further optimization is needed to enhance implant retention and ensure long-term functional integration.