Accelerating AF repair with a multi-factor mechanoactive patch

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Intervertebral disc herniations, caused by extrusion of nucleus pulposus tissue through a defect in the annulus fibrosus (AF), affect 2 to 3% of the world population and can be a significant contributor to back pain and disability. The gold standard clinical treatment for patients with persistent pain from disc herniation that is unresolved after conservative treatment is microdiscectomy surgery, during which the herniated tissue is removed to relieve pressure on the nerve roots. However, the AF is not surgically repaired during this procedure. Given the limited endogenous healing capacity of the AF, 10 to 30% of patients will experience a symptomatic recurrent herniation. Due to the clinical burden of disc herniations and the absence of alternatives to discectomy, there is a substantial need to develop and translate novel AF repair devices which can facilitate annular healing, restore disc mechanics, and prevent re-herniation. Endogenous repair following injury is hindered by AF cell apoptosis, increased local inflammation and ultimately the formation of disorganized scar tissue. Repair strategies that address this complex biological milieu, while restoring AF mechanical function and preventing re- herniation have yet to be established and proven efficacious in large animal studies. Here, we will optimize and translate a novel tension-activated annular repair scaffold (TARS) to address both the structural and biological requirements for annular repair. The TARS implants are composed of two layers of aligned nanofibrous polymer scaffolds, containing depots of microcapsules between the scaffold layers which release their contents under mechanical loading (MAMCs). When the TARS is loaded in tension, the MAMCs are compressed, leading to release of bioactive molecules. In Aim 1, we will define the release profiles of the TARS in vitro under dynamic uniaxial tensile loading in a physiologic environment, and in situ when affixed to the AF in cadaveric goat cervical spine motion segments. From this Aim, we will validate a TARS design that can deliver bioactive molecules to the repair site over acute and chronic timescales. In Aim 2, we will target the biological sequalae of annular injury and evaluate the ability of an anti-inflammatory and pro-anabolic TARS to promote local AF repair and global spine functional restoration in vivo in a goat cervical disc injury model. AF injury and repair will be thoroughly evaluated across length scales, with a focus on the restoration of healthy AF structure, biology and mechanical function. This novel and translationally relevant AF repair technology could change clinical practice for the treatment of disc herniations, reduce the incidence of reherniation, and improve the long-term spine health of patients.