Dr. Hussain is now presenting. He should be acknowledged for receiving the Stuart Dunsker Award. Thank you. Good afternoon, everybody. Thank you for having me. I'm Ibrahim Hussain, PGY5 from New York. These are our disclosures. So 300,000 discectomies are performed annually every year in the United States. As many of you are aware, the annulus fibrosis is usually not repaired at the time of surgery. Recurrent disc herniations can occur in anywhere from 3 to 10 percent of cases, and studies have shown that this correlates with the size of the annular defect. Mechanical solutions, including suturing and butchering devices, have failed to show any benefit in recent clinical trials. To this end, biologic approaches for annular repair have become of increasing interest. Collaborating with a group of bioengineers in Cornell University, over the past six years we've developed a high-density collagen gel that's formulated with riboflavin that once exposed to blue light for 40 seconds cross-links the riboflavin and stiffens the gel. We've been able to show in vitro and more recently in vivo efficacy of this gel in rat tail and recently in a large animal sheep model. More specifically, we've been able to show that this collagen gel plugs the annular defect, reconstitutes the annular structure, and prevents microscopic features of disc degeneration. However, specifically with our sheep model, we were able to only show limited radiographic differences between the treated and untreated discs. Therefore, we wanted to ask if cellular augmentation of the high-density collagen gel could improve its efficacy. Mosaicom stem cells have had a plethora of publications over the past decade, both in vitro, in vivo, and recently human clinical trials for their efficacy in disc regeneration. Specifically, this has been accomplished through their ability to regulate genes germane to extracellular matrix degradative enzymes and also for their ability to differentiate into chondroblasts, which can then stimulate further regeneration. We harvested mosaicom stem cells from sheep femoral bone marrow and were able to show that these cells can actually survive when seeded onto our high-density collagen gel. For our study, I experimented with 15 intervertebral discs from three sheep that were randomized into one of four groups, either intact, injury only, injury plus treatment with an acellular high-density collagen gel, or injury plus treatment with a mosaicom stem cell seeded high-density collagen gel. We followed these animals out to six weeks and then performed various radiographic and histologic studies, and all results were ultimately calculated as ratios to intact discs from the same sheep to eliminate for variation. This is an intraoperative photo showing the approach that I used. It was essentially a lateral retroperitoneal presoas approach to the lateral aspect of the sheep lumbar spine. It's most analogous to an O-LIF approach that would be performed in humans. Intraoperative photo showing the actual defect, followed by the annulotomy plus discectomy, and then followed by the defect being filled with the collagen gel after it's been cross-linked. For our first set of results, we performed T2 MRIs to try to determine the Furman grade, and again, looking at the last column, you could see that compared to the other experimental groups, the disc treated with mosaicom stem cell collagen gel performed better than the other groups, however, did not reach that of the intact discs. We also performed quantitative MRI studies, including T2 relaxation time, which serves as a surrogate for nucleus pulposus hydration or disc health, and again, looking at the last column, we're able to show that the results were improved with the treatment of mosaicom stem cell treated high-density collagen gel. We also performed histologic studies and performed quantitative histologic analysis using the Hahn grading scale, and if you compare the second row with the last row, again, you can see that there's less vacuolization, degeneration of the nucleus pulposus, less end plate changes, and more reconstitution of the actual annular structure. So in conclusion, we were able to show that there were no adverse immunologic reactions to the gel, that we were able to perform a reproducible and safe surgical operation. There was significant improvement in annular restructuring and mitigation of disc degeneration in the high-density collagen gel treated discs over the untreated discs, and more specifically, we were able to show that the mosaicom stem cell treated discs demonstrated a trend towards improved outcomes over the acellular formulation. Looking ahead to the future, I've operated on 40 other discs from eight other sheets that are walking around right now. We're going to follow them out to 16 weeks. We've fluorescently labeled the mosaicom stem cells to determine their ultimate fate. A subset will be sacrificed solely for biomechanical studies. And working with a group of engineers from Cornell, we've also patented a device that could actually allow us to deliver the gel through a tubular retractor, which is the ultimate end goal if we want to test it in humans. I'd like to thank Roger Hartle, Larry Benasser, the rest of my team, and that's all. Thank you. Applause.

annular repair

collagen gel

disc degeneration

stem cells

device development