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

这个i-Corps项目的更广泛的影响/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，包括止痛药和消炎药，只能缓解症状，而不能治愈疾病。到目前为止，黄金疗法是使用自体软骨替代性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、感染和有限的组织供应等问题。因此，客户对能够促进软骨愈合、增强骨性关节炎治疗疗效的技术有着强烈的需求。此外，目前的骨性关节炎治疗费用昂贵，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项目是基于一种可生物降解的压电组织支架的开发，该支架由电纺聚L乳酸(PLLA)制成，用于软骨修复。目前，传统的压电材料如锆钛酸铅(PZT)、聚偏氟乙烯(PVDF)和钛酸钡都是有毒和/或不可降解的。由于安全问题和侵入性切除手术的要求，这些特性使其不利于某些应用，例如再生医学。与这些材料不同，PLLA是一种很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，要将PLLA加工成一种简单易用、具有高效和稳定的压电性的形式用于实际应用是具有挑战性的。这项拟议的技术是基于一种材料工艺，以创造可生物降解的、灵活的PLLA纳米膜，具有可控的和出色的压电响应。这种压电纳米膜可能是一种安全的平台，用于生物可吸收的、无电池的组织移植，能够产生电荷促进软骨愈合，并提高骨关节炎治疗的效果。结果表明，在康复活动或锻炼过程中施加关节载荷的动物模型中，在临界大小的骨软骨缺损中测试的压电PLLA支架可以作为一种无电池的电刺激器来促进软骨愈合。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.