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Background: A biodegradable polyurethane scaffold was developed to treat patients with the challenging clinical condition of painful partial meniscal defects. Hypothesis: The use of an acellular polyurethane scaffold in patients with symptomatic partial meniscal defects would result in both midterm pain relief and improved function. Study Design: Case series; Level of evidence, 4. Methods: A total of 155 patients with symptomatic partial meniscal defects (101 medial and 54 lateral) were implanted with a polyurethane scaffold in a prospective, single-arm, multicentric study with a minimum 5-year follow-up. Clinical outcomes were measured with the visual analog scale for pain, International Knee Documentation Committee subjective knee evaluation form, Lysholm knee scale, and Knee injury and Osteoarthritis Outcome Score at baseline and at 2- and 5-year follow-ups. Magnetic resonance imaging (MRI) was used to evaluate the knee joint, meniscal implant, and meniscal extrusion. Kaplan-Meier survival analysis was also performed. Removal of the scaffold, conversion to a meniscal transplant, and unicompartmental/total knee arthroplasty were used as endpoints. Results: Eighteen patients were lost to follow-up (11.6%). The patients who were included in this study showed significant clinical improvement after surgery as indicated by the different outcome measures (P =.01). However, the clinical improvement tended to stabilize between 2 and 5 years of follow-up. MRI scans of the scaffolds in 56 patients showed a smaller-sized implant in the majority of the cases when compared with the native meniscus with an irregular surface at the 5-year follow-up. During the follow-up period, 87.6% of the implants survived in this study. At 5 years of follow-up, 87.9% of the medial scaffolds were still functioning versus 86.9% of the lateral scaffolds. In total, 23 treatments had failed: 10 removed scaffolds because of breakage, 7 conversions to meniscal allograft transplantation, 4 conversions to unicompartmental knee arthroplasty, and 2 conversions to total knee arthroplasty. Conclusion: The polyurethane meniscal implant was able to improve knee joint function and reduce pain in patients with segmental meniscal deficiency over 5 years after implantation. The MRI appearance of this scaffold was different from the original meniscal tissue at the midterm follow-up. The treatment survival rates of 87.9% of the medial scaffolds and 86.9% of the lateral scaffolds in the present study compared favorably with those published concerning meniscal allograft transplantation after total meniscectomy. [ABSTRACT FROM AUTHOR]