Symptomatic lumbar disc herniations occur in 0.5 to 2 % of the adult population annually, with a higher incidence in individual exposed to strenuous activities in their work environments, including active duty military personnel. A lumbar microdiscectomy is very effective at addressing the extruded disc fragment and alleviating radicular leg pain. However, there is currently no established method to repair the annular defect. The injured annulus fibrosus has altered mechanical properties, and it is well recognized that larger annular defects are associated with an increased risk of recurrent disc herniation at that interspace. With this loss of AF function, the motion segment is also at risk for further degeneration, and loss of disc space height and further degeneration is a common sequelae of lumbar disc herniations. There are currently no effective clinical interventions targeted at repairing the annulus fibrous in a manner that recapitulates the native disc. The objective of this project is to develop a novel tension activated annular repair scaffold (TARS) to treat defects in the annulus fibrosus (AF) associated with herniations, with the goal of closing the annular defect and stimulating native tissue repair to restore disc mechanical function.
Three Specific Aims are pursued:
Two Specific Aims are pursued:
Specific Aim 1 : Develop tension-actuated AF repair scaffolds. A novel mechanically activated microcapsule (MAMC) will be included in electrospun scaffolds to create the TARS. Scaffold properties and MAMC attributes will be varied to optimize material fabrication and to tune release in response to tensile loading. We will create two classes of MAMCs: 1) containing chemotactic cell recruitment agents designed to activate under low levels of physiologic loading and 2) matrix-promoting agents housed within MAMCs designed to burst sequentially with long term loading. Both populations will include an anti-inflammatory agent to improve regeneration. Bioactivity of the MAMCs will also be confirmed via in vitro bioreactor assays.
Specific Aim 2 : Evaluate the TARS in models of intervertebral disc repair under physiologic loading. Box defects in the AF will be created in cadaveric goat spinal motion segments, and the TARS sutured in place. Ex vivo, multi- axial (compression, flexion, extension and torsion) dynamic loading will be applied to demonstrate that physiologic spinal loading causes sequential release from the two MAMC populations. Outcomes will include confocal microscopy analysis of MAMC release and analysis of motion segment mechanical properties. Next, we will carry out a pilot study in our goat cervical spine model in which the in vivo repair capacity of the TARS will be evaluated. Outcomes at 3 months will include histological analysis of the scaffold and cell infiltration and MRI and mechanical properties of the repaired motion segment.It is anticipated that the proposed study will yield a novel repair for defects of the AF and an increased understanding of the mechanobiology of the IVD. This novel treatment may decrease the risk of recurrent herniations and offer a new clinical paradigm.
The objective of this SPiRE proposal is to develop a novel repair strategy for annular defects to restore the mechanical function of the annulus fibrosus at the time of surgery for disc herniation. For this, we will develop and apply a new tension-activated electrospun scaffold that incorporates mechanically activated microcapsules to release factors at the time of implantation during early repair to promote tissue integration and matrix formation. If successful, this work will advance the treatment options for disc herniation and set the stage for translation to human clinical trials.
