I-Corps: Biodegradable Piezoelectric Cartilage Graft with Physical Exercise for Osteoarthritis Treatment

这个I-Corps项目更广泛的影响/商业潜力是开发一种可生物降解的压电组织支架，用于促进软骨愈合。超过3250万美国成年人患有骨关节炎（OA），这是最常见的慢性关节疾病。然而，目前的药物，包括止痛药和抗炎药，只能缓解症状，但不能治愈疾病。到目前为止，最好的治疗方法是使用软骨自体移植或同种异体移植。然而，这些移植物与供体部位发病、免疫排斥、感染和有限的组织供应的问题作斗争。因此，客户对能够促进软骨愈合和增强OA治疗效果的技术有着强烈的需求。此外，目前的OA治疗费用昂贵，估计每位患者每年的费用为16000美元。因此，骨关节炎患病率的增加为新治疗提供了巨大的市场机会。这个I-Corps项目是基于开发一种可生物降解的压电组织支架，该支架由电纺聚L-乳酸（PLLA）制成，用于软骨修复。目前，传统的压电材料，例如锆钛酸铅（PZT）、聚偏氟乙烯（PVDF）和钛酸钡，要么有毒，要么不可降解。这些性质使得它们不适合某些应用，例如再生医学，这是由于安全性问题和侵入性去除手术的要求。 与这些材料不同，PLLA是一种有吸引力的替代压电生物材料，因为它是安全的和可生物降解的。然而，将PLLA加工成易于使用的形式并具有用于实际应用的高效和稳定的压电性是具有挑战性的。 该技术基于材料工艺，以创建可生物降解的柔性PLLA纳米膜，该纳米膜具有可控和出色的压电响应。这种压电纳米膜可能是生物可吸收的无电池组织移植物的安全平台，该组织移植物能够产生电荷以促进软骨愈合并增强骨关节炎治疗的功效。 结果表明，在康复活动或运动期间施加关节负荷的动物模型中，在临界尺寸的骨软骨缺损中测试的压电PLLA支架可以作为无电池电刺激器促进软骨愈合。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this I-Corps project is the development of a biodegradable piezoelectric tissue scaffold for promoting cartilage healing. More than 32.5 million American adults suffer from osteoarthritis (OA), which is the most common chronic joint condition. Yet current medicines, including analgesics and anti-inflammatory drugs, only alleviate symptoms but do not cure the disease. The golden treatment so far has been to use replacement cartilage autografts or allografts. These grafts, however, struggle with problems of donor site morbidity, immune rejection, infection, and limited tissue supply. Therefore, there is a strong customer need for technology that can promote the healing of cartilage and enhance OA treatment efficacy. Additionally, the current OA treatments are expensive, with an estimated annual cost of $16 000 per patient. As such, the increasing prevalence of osteoarthritis presents a substantial market opportunity for new treatments. This I-Corps project is based on the development of a biodegradable piezoelectric tissue scaffold made from electrospun poly-L-lactic acid (PLLA) for use in cartilage repair. Currently, conventional piezoelectric materials such as lead zirconate titanate (PZT), polyvinylidene fluoride (PVDF), and barium titanate are either toxic and/or non-degradable. These properties render them unfavorable for certain applications, such as for regenerative medicine, due to the safety concern and the requirement for invasive removal surgery. Unlike these materials, PLLA is an attractive alternative piezoelectric biomaterial as it is safe and biodegradable. However, it is challenging to process PLLA into an easy-to-use form with highly effective and stable piezoelectricity for practical applications. The proposed technology is based on a materials process to create biodegradable, flexible PLLA nanomembranes that possess a controllable and outstanding piezoelectric response. This piezoelectric nanomembrane may be a safe platform for a bioresorbable, battery-less tissue graft that is able to generate electrical charge to promote the healing of cartilage and enhance the efficacy of osteoarthritis treatment. Results show that the piezoelectric PLLA scaffold tested in critical-sized osteochondral defects in an animal model under applied joint-load during rehabilitation activities or doing exercise may act as a battery-free electrical stimulator to promote cartilage healing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.