Date of Award
Master of Science (MS)
Jeremy J Mercuri
The intervertebral disc (IVD) is a fibrocartilaginous tissue connecting adjacent vertebrae in the spinal column. Within the IVD is gelatinous core called the nucleus pulposus (NP) which is radially confined by the annulus fibrosus (AF). The AF is composed of concentric layers of fibrous lamellae rich in collagen type I and functions to support radial forces redistributed from the NP core. Pathologic conditions of the IVD are often associated with low back pain (LBP) which has a lifetime prevalence of up to 80% and creates an annual economic burden of over $100 billion. Discogenic pathologies associated with LBP include IVD degeneration (IVDD – a multifactorial breakdown of the IVD) and/or herniation (IVDH – when IVD tissue is forced beyond or out of the normal confines of the IVD). This results in approximately 2.7 million back surgeries in the United States annually. These surgeries are generally palliative, leaving patients susceptible to continued chronic LBP or chance of re-herniation.
Current methods aimed at repairing the IVD fail to address the focal defect created in the AF following discectomy. Furthermore, developing technologies that do effectively close AF defects (Intrinsic Barricaid™ and Annulex X-Close™) are made of synthetic materials that do not support IVD tissue regeneration. Therefore, there has been an increased focus on using tissue engineering and regenerative therapies to develop an effective AF repair system to both restore IVD integrity and mechanics to slow or halt underlying degenerative processes.
Our group has previously developed an outer AF repair patch (AFRP) using sheets of decellularized pericardium. Pericardium contains collagen type I and a fiber orientation similar to native AF tissue. Stacking layers of fiber aligned pericardium effectively mimics the angle-ply lamellae of the AF. Despite many promising outcomes of the AFRP, it was identified that a biomimetic scaffold was needed that could fill a full-thickness AF defect, as opposed to only covering the defect in the outer AF. Thus, the goals of this research were to i) fabricate a full thickness, multi laminate annulus fibrosus repair plug (FT-AFRP) scaffold, ii) determine the scaffold’s ability to mimic the mechanical properties of native, full-thickness AF tissue and restore spinal kinematics in a repair model, iii) determine the scaffold’s influence on AF cell viability, alignment, and morphology.
The research herein resulted in the development of a repeatable method to fabricate FT-AFRPs which effectively mimicked the angle-ply, fiber aligned architecture of native AF using decellularized pericardium and an alginate hydrogel casing. FT-AFRPs moderately matched compressive mechanical properties of native AF tissue and partially restored spinal kinematic parameters in an IVD explant repair model. FT-AFRPs also demonstrated cytocompatibility and the ability to support AF cell alignment and morphology. Collectively, these results support the potential of the FT-AFRP to be used in conjunction with outer AF closure techniques to more effectively repair the AF following IVD surgery.
Garon, Alex, "The Fabrication and Analysis of an Angle-Ply, Multi-Laminate Annulus Fibrosus Plug for Intervertebral Disc Repair" (2020). All Theses. 3276.