The effectiveness of small intestinal submucosa for spinal ligament repair in the goat

Abstract

Allen L. Carl, MD, Eric H. Ledet, MS, Darryl DiRisio, MD, Michael P. Tymeson, MS, Lucille B. Andersen, MD, Bashkar Kallarury, MD, Albany, NY, USA; Michael Slivka, Hassan Serhan, PhD, Raynham, MA, USABackground context: Destabilization of the lumbar spine results from sacrifice of the anterior longitudinal ligament and disc when removed for graft or cage placement. Similarly, transection of the interspinous ligament during surgical approaches to the posterior spine may result in additional instability. Such instability can cause abnormal motion or implant migration resulting in a high incidence of pseudarthrosis. Small intestinal submucosa (SIS) is a naturally occurring extracellular collagen-based matrix, which is derived from the small intestine of pigs. SIS contains cytokines and growth factors and has been shown to act as a resorbable scaffold in vivo that promotes soft tissue regeneration with little scar tissue formation. SIS can be manufactured in laminated sheets of various sizes and thicknesses for different indications. Successful applications of SIS have included dural substitution, rotator cuff repair, tendinosis, vessel repair, abdominal and bladder wall repair and others. However, SIS has not been investigated to determine its ability to facilitate regeneration of spinal ligaments.Purpose: The purpose of this pilot study was to evaluate the efficacy of SIS to restore stability in the spine and act as a scaffold for regeneration of the anterior longitudinal ligament (ALL) and interspinous ligaments (ISL) in a goat model.Methods: Four skeletally mature nubian-alpine crossbred goats were used in this study. Under general anesthesia, each T10 to L5 motion segment was exposed surgically. Both an anteriolateral and posterior approach were made at each level. Anteriorly, every other level received either anterior discectomy, sacrifice of ALL and placement of SIS (”SIS”); anterior discectomy, sacrifice of ALL and no SIS (”control”); or sham operation (”sham”). A solid interbody spacer was placed into the disc space at each SIS and control level to prohibit spontaneous anterior interbody fusion. A sheet of SIS was applied to the ventral surface of each SIS level such that it spanned the disc space making intimate contact with the remaining ALL superiorly and inferiorly. The SIS was secured to the cranial and caudal vertebral bodies with bone staples, suture anchors and suture. Posteriorly, every other level received either sacrifice of the ISL with placement of SIS (”SIS”); sacrifice of ISL and no SIS (”control”); or sham operation (”sham”). At SIS levels, a sheet of SIS was applied dorsal to the spinous processes and wrapped over the left and right lateral aspect. The SIS was secured to the spinous processes with suture anchors. Sutures were passed through the SIS and around the adjacent spinous processes to create a tension-band effect. Animals were radiographed immediately postoperatively to confirm implant placement and to serve as a baseline for interbody spacer positioning. After surgery, all animals were allowed unrestricted motion for 12 weeks. At the end of the 12-week period, animals were radiographed and euthanized. The lumbar spine was harvested en bloc and processed for decalcified histologic evaluation. The dorsal and ventral aspects of each motion segment were analyzed for signs of inflammation and scar tissue formation, residual SIS and regenerated ALL or ISL.Results: All animals tolerated the surgical procedure well, and there were no intraoperative or anesthesia related complications. Immediate postoperative radiographs showed proper placement of all implants. Gross analysis at necropsy indicated iatrogenic scar formation, the degree of which was not different from controls to SIS levels. Histologic evaluation of areas where the ALL had been removed indicated formation of organized fibrillar collagenous tissue that spanned the disc space at some levels where the SIS was placed. The newly formed tissue was approximately 70% the thickness of the ALL at the sham level. Sparse focal areas of inflammation and no residual SIS at some levels accompanied the newly formed collagenous tissue. At control levels, there was limited formation of sparsely organized connective tissues. At sham levels, normal ligamentous structures were present. Similarly, histologic analysis of some levels where SIS was placed posteriorly showed formation of organized collagenous tissues where the ISL had been removed.Discussion: Placement of the SIS resulted in regeneration of the ligamentous-like tissues in the spine to a varying degree with limited signs of inflammation and scar formation. This result indicates the potential for SIS in repair of spinal ligaments for restabilization of the lumbar spine.