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

I-Corps项目更广泛的影响/商业潜力是开发促进软骨愈合的可生物降解压电组织支架。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，包括止痛药和消炎药，只能缓解症状，而不能治愈这种疾病。目前的黄金疗法是自体软骨移植或同种异体软骨移植。然而，这些移植物面临供体部位发病率、免疫排斥、感染和组织供应有限等问题。因此，客户对能够促进软骨愈合，提高OA治疗疗效的技术有强烈的需求。此外，目前的OA治疗费用昂贵，估计每位患者每年的费用为1.6万美元。因此，骨关节炎的日益流行为新的治疗方法提供了大量的市场机会。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，这种支架由静电纺聚l -乳酸（PLLA）制成，用于软骨修复。目前，传统的压电材料，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。这些特性使得它们不适合某些应用，如再生医学，由于安全问题和侵入性去除手术的要求。与这些材料不同，pla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，在实际应用中，将PLLA加工成易于使用且具有高效和稳定压电性的形式是具有挑战性的。所提出的技术是基于一种材料工艺来制造可生物降解的、柔性的PLLA纳米膜，这种膜具有可控和出色的压电响应。这种压电纳米膜可能是一种可生物吸收的、无电池的组织移植物的安全平台，这种移植物能够产生电荷，促进软骨的愈合，提高骨关节炎的治疗效果。结果表明，在康复活动或运动期间施加关节载荷的情况下，在动物模型中对临界尺寸骨软骨缺损进行的压电式PLLA支架测试可以作为无电池电刺激器促进软骨愈合。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识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.