Defects in the annulus fibrosus (AF) of intervertebral discs allow nucleus pulposus tissue to herniate causing painful disability. Microdiscectomy procedures remove herniated tissue fragments but unrepaired defects remain allowing reherniation or progressive degeneration. Cell therapies show promise to enhance repair but methods are undeveloped and carriers are required to prevent cell leakage. To address this challenge, this study developed and evaluated genipin-crosslinked fibrin (FibGen) as an adhesive cell carrier optimized for AF repair that can deliver cells, match AF material properties and have low risk of extrusion during loading. Part 1 determined feasibility of bovine AF cells encapsulated in high concentration FibGen (F140G6: 140mg/ml fibrinogen; 6mg/ml genipin) for 7 weeks could maintain high viability, but had little proliferation or matrix deposition. Part 2 screened tissue mechanics and in situ failure testing of nine FibGen formulations (fibrin: 35-140mg/ml; genipin: 1-6 mg/ml). F140G6 formulation matched AF shear and compressive properties and significantly improved failure strength in situ. Formulations with reduced genipin also exhibited satisfactory material properties and failure behaviors warranting further biological screening. Part 3 screened AF cells encapsulated in four FibGen formulations for one-week and found reduced genipin concentrations increased cell viability and glycosaminoglycan production. F70G1 (70mg/ml fibrinogen; 1mg/ml genipin) demonstrated balanced biological and biomechanical performance warranting further testing. We conclude that FibGen has potential to serve as an adhesive cell carrier to repair AF defects with formulations that can be tuned to enhance biomechanical and biological performance; future studies are required to develop strategies to enhance matrix production.

Study Design: Meta-analysis. Objectives: To assess return to play (RTP) rates in adolescent athletes with lumbar spondylolysis without spondylolisthesis treated conservatively or operatively. Methods: A review of Medline, EMBASE, and Cochrane Reviews was performed. The pooled results were performed by calculating the effect size based on the logit event rate. Studies were weighted by the inverse of the variance. Confidence intervals were reported at 95%. Heterogeneity was assessed using the Q statistic and I² value. Results: The initial literature search resulted in 724 articles, of which 29 were deemed relevant on abstract review. Overall, 11 studies provided data for 376 patients with a pars interarticularis defect. Return to athletic competition, based on logit event rate, was found to be statistically favored after both nonoperative and operative treatment (92.2% vs 90.3%). There was no heterogeneity noted among the studies reporting nonoperative treatment ( Q value of 4.99 and I² value of 0). There was mild heterogeneity within the operative studies ( Q value of 3.54 and I² value of 15.18). Conclusions: Adolescent athletes RTP 92.2% of the time with nonoperative management, compared with 90.3% when treated operatively, though both treatment groups strongly favor RTP. As this is the first study to pool results of all relevant literature, it provides strong evidence to guide decision making and help manage expectations in this unique patient population.