A pilot study to evaluate the effectiveness of small intestinal submucosa used to repair spinal ligaments in the goat.
BACKGROUND
Destabilization of the lumbar spine results from sacrifice of the anterior longitudinal ligament and disc when removed for graft or cage placement. In a similar fashion, transection of the interspinous ligament during surgical approaches to the posterior spine may result in segmental instability. Such instability can cause abnormal motion or implant migration resulting in a higher incidence of pseudarthrosis. Small intestinal submucosa (SIS) is a naturally occurring extracellular collagen-based matrix, which is derived from porcine small intestine. SIS contains cytokines and growth factors and has been shown to act as a resorbable scaffold in vivo that promotes host 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 in animals have included dural substitution, rotator cuff repair, 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.


OBJECTIVE
The purpose of this pilot study was to evaluate the efficacy of SIS as a barrier to prevent interbody device migration, and to act as a scaffold for regeneration of the anterior longitudinal ligament (ALL) and posterior interspinous ligament (PISL) in a goat model.


METHODS
The thoracolumbar spine of the goat was exposed surgically. After resection and removal of the ALL or PISL at alternating levels, either SIS was placed or no treatment was administered. New ligament formation and SIS resorption were monitored over a 12-week period.


METHODS
Plain film radiographs and histomorphometry were used to assess the progress of healing over a 12-week time period.


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 anterolateral and posterior approaches were performed simultaneously at each level. Anteriorly, alternating levels received either 1) anterior discectomy, sacrifice of ALL and placement of SIS (SIS group); 2) anterior discectomy, sacrifice of ALL and no SIS (surgical control group) or 3) no surgical intervention (nonoperative group). A solid interbody spacer was placed into the disc space after discectomy to deter spontaneous anterior interbody fusion. Posteriorly, alternating levels were treated with either 1) sacrifice of the PISL with placement of SIS (SIS group); 2) sacrifice of PISL and no SIS (surgical control group) or 3) no surgical intervention (nonoperative group). The SIS was secured to the adjacent superior and inferior spinous processes to create a tension-band effect. Animals were radiographed immediately postoperatively to confirm placement of interbody spacers and anchors and to serve as a baseline for monitoring 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 PISL.


RESULTS
All animals tolerated the surgical procedure well, and there were no intraoperative or anesthesia-related complications. Twelve-week radiographs showed some evidence of ventral migration of the interbody spacers in several animals. Fifty percent (two of four) of spacers in surgical control group levels had migrated more than 10 mm (resulting in complete migration out of the disc space), whereas no spacers migrated completely out of levels with SIS placed. Gross analysis at necropsy indicated iatrogenic scar formation at operated levels, the degree of which was not different from surgical control group to SIS levels. Histologic evaluation of areas where the ALL had been removed indicated formation of organized fibrilar collagenous tissue that spanned the disc space at some levels where the SIS was placed. In some cases, the newly formed tissue was approximately the thickness of the ALL at the nonoperative group levels. The newly formed collagenous tissue was accompanied by sparse focal areas of inflammation, with small fragments of residual SIS at some levels. At surgical control group levels, there was a varying degree of connective tissue that ranged from moderately organized to randomly oriented with no significant signs of inflammation. Similarly, histologic analysis of some levels where SIS was placed posteriorly showed formation of organized collagenous tissues where the PISL had been removed.


CONCLUSIONS
In this model, the SIS patch was sufficient to prevent acute ventral migration of interbody spacers from the disc space. The extent of long-term healing and new tissue formation in the SIS group indicates that it may be efficacious as a reparative intervention for transected ligaments in the spine. Most SIS specimens showed formation of organized collagenous tissue, indicating a long-term potential for ligament formation. However, in this model, 12 weeks of postoperative healing is insufficient to assess the full potential of SIS as a spinal ligament repair. Further research that follows the healing process to a longer time point postoperatively may be necessary to fully understand the potential of SIS as a resorbable scaffold for tissue replacement.
Ledet
Eric H
EH
Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA. ledete@mail.amc.edu
Carl
Allen L
AL
DiRisio
Darryl J
DJ
Tymeson
Michael P
MP
Andersen
Lucille B
LB
Sheehan
Christine E
CE
Kallakury
Bhaskar
B
Slivka
Michael
M
Serhan
Hassan
H
D020341:Absorbable Implants; D000818:Animals; D017586:Diskectomy; D005548:Foreign-Body Migration / Q000517:prevention & control*; D006041:Goats; D007403:Intervertebral Disc / Q000601:surgery; D007413:Intestinal Mucosa / Q000637:transplantation*; D007421:Intestine, Small / Q000637:transplantation; D007593:Joint Instability / Q000601:surgery*; D017846:Longitudinal Ligaments / Q000473:pathology / Q000502:physiology* / Q000601:surgery; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D008297:Male; D010865:Pilot Projects; D011859:Radiography; D012038:Regeneration / Q000502:physiology*