SBIR Phase I: Arthroscopy Delivered Scaffolds to Repair and Regenerate Meniscus for Aging Patients

这项小企业创新研究（SBIR）一期项目的更广泛影响/商业潜力是预防或降低半月板部分切除术后半月板切除术后骨关节炎（OA）的高风险，这是半月板撕裂的一种常用治疗方法。半月板撕裂是一种常见的病变损伤，在年龄在45岁及以上的人群中普遍存在~36%，但有效的治疗方法很少。半月板切除术是为了暂时缓解剧烈疼痛和其他与半月板撕裂相关的症状。在美国，每年有超过100万患者接受半月板切除术以缓解半月板撕裂相关的疼痛症状。半月板切除术的缺点是在生命后期骨关节炎（OA）的发病率显著增加（高达7倍），因为半月板的丢失会导致负荷传递改变，减震，关节稳定性下降和关节软骨接触应力增加。半月板切除术后骨关节炎（OA）在文献中有很好的记录。OA的治疗更具挑战性，花费更高，给患者带来更严重的身体痛苦。迫切需要有效治疗半月板撕裂，同时减少或预防半月板切除术后的风险。如果成功，该项目可能会通过开发一种精确修复和再生撕裂半月板并恢复生物力学功能的设备，潜在地解决未满足的临床需求。没有现有的知识告诉我们老化的关节环境如何影响半月板的修复和再生，申请人也没有。先前的研究可以告诉他们的新设备在老化关节中的表现；目前还不清楚科学证据和必要的技术解决方案。目前的I期研究将：1)确定在老化膝盖中刺激修复干细胞的递送策略；2)使用体外评估模型确定在额外炎症应激下的递送策略。该研究是未来将该技术转化为临床应用的概念验证的关键一步。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to prevent or reduce the high risk of post-meniscectomy osteoarthritis (OA) following partial meniscectomy which is a popular treatment for meniscus tears. Meniscus tears represent common lesions injuries prevailing in ~36% of people with ages at and greater than 45 years old, but with few effective treatments. Meniscectomy is performed to temporarily relieve the severe pain and other symptoms associated with meniscus tears. Over one million patients undergo meniscectomy to palliate painful symptoms associating torn meniscus each year in the U.S. The drawback of meniscectomy is significant increases of incidence of osteoarthritis (OA) later in life (by as high as 7 folds), because loss of meniscus causes altered load transmission, decreased shock absorption, and decreased joint stability and increased joint cartilage contact stress. Post-meniscectomy osteoarthritis (OA) is well documented in literatures. OA is more challenging to treat and incur more costly expenditures and causes more severe physical sufferings for patients. There is urgent need for effective treatment for meniscus tears while reducing or preventing the poste-meniscectomy risks. The proposed project could, if successful, potentially address the unmet clinical need by developing a device precisely repairing and regenerating the torn meniscus and restoring the biomechanical functionality. No existing knowledge teaches how an aging joint environment may affect the meniscal repair and regeneration, and neither the applicants? previous study can tell how their new device may perform in the aging joints; both scientific evidence and necessary technical solutions are unclear yet. The present Phase I study will: 1) determine the delivery strategy to stimulate reparative stem cells in aging knees, and 2) determine the delivery strategy under additional inflammatory stress, using in vitro evaluation models. The study serves as a critical step of proof-of-concept for future translation of the technology into a clinical application.