Histotripsy for collagenous tissues: a novel therapeutic approach to tendon injury

胶原组织的组织解剖学：一种治疗肌腱损伤的新方法

• 批准号: 10113612
• 负责人: Julianna Simon
• 金额: $ 21.52万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-09 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10113612
• 关键词: Accounting; Address; Adoption; Adult; Aftercare; Animal Model; Animals; Biological Markers; Blood capillaries; Blood specimen; Clinical; Clinical Treatment; Collagen; Contralateral; Development; Elastic Tissue; Elements; Exposure to; Failure; Focused Ultrasound Therapy; Frequencies; Future; Gel; Goals; Heart; Heating; Histologic; Human; Immune response; Inflammation; Injury; Intervention; Joint structure of shoulder region; Length; Limb structure; Liver; Mechanics; Medical; Methods; Modality; Modeling; Muscle; Musculoskeletal Pain; Needles; Operative Surgical Procedures; Organ; Outcome; Patients; Physiologic pulse; Prevalence; Property; Protocols documentation; Puncture procedure; Rattus; Relaxation; Resistance; Role; Rotator Cuff; Sampling; Shock; Shoulder Pain; Source; Stress; Techniques; Tendon Injuries; Tendon structure; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Treatment Cost; Treatment Protocols; Ultrasonography; Upper Extremity; Work; clinical development; clinical translation; cohort; common treatment; experience; healing; human model; improved; in vivo; injured; innovation; joint mobilization; mechanical load; mechanical properties; millisecond; musculoskeletal injury; novel; novel therapeutic intervention; pressure; repaired; response; rotator cuff tear; success; supraspinatus muscle; technique development; tissue injury; tool; treatment site

PROJECT SUMMARY/ABSTRACT High intensity focused ultrasound (HIFU) modalities, such as histotripsy, have been used successfully to emulsify soft organs, like the heart and liver, but highly collagenous tissues, like tendons, have proven resistant to mechanical emulsification with histotripsy. Recently, histotripsy was shown to initiate an immune response and release biomarkers. If histotripsy can successfully emulsify collagenous tissues, it has the potential to initiate a healing response by inducing inflammation and subsequently release healing factors. With the high clinical prevalence of tendon injuries, establishing whether histotripsy can create microdamage in collagenous tendons to promote healing has the potential for long-term impact. Rotator cuff tear is a highly prevalent cause of shoulder pain, which is why patients seek medical treatment. Surgical repair is a common treatment for rotator cuff tear, but fails up to 90% of the time, likely from the high mechanical loading the rotator cuff experiences in its dual roles with joint mobility and stability. Others have used dry needling (DN), which involves repeated puncturing of the tendon with a fine-gauge needle to induce microdamage and release healing factors, but adoption of this approach is not wide-spread. Development of techniques that can noninvasively promote healing while maintaining mechanical integrity of the muscle-tendon units are desperately needed. Demonstration of histotripsy therapy for collagenous tissue emulsification would provide a clinically transferrable tool to immediately supplement current treatment options of a contemporary clinical problem. Here, we propose to establish non-invasive histotripsy protocols that produce better indicators of tendon healing compared to DN, while simultaneously maintaining tendon's mechanical properties. These goals will be accomplished by: 1) testing novel histotripsy protocols to induce microdamage in collagen gels and ex vivo rat tendons; 2) evaluating the mechanical properties of tendon following histotripsy and DN, and develop a finite element model to evaluate parameters and perform predictive analyses; and 3) determining whether histotripsy enhances collagenous tissue healing in vivo in a pilot survival study in rats. This innovative work seeks to demonstrate that histotripsy can successfully emulsify collagenous tissues, and enhance the release of healing factors. Once feasibility has been demonstrated, the methods and models developed in this project will be scaled to examine histotripsy in larger animal models and humans. Long term, outcomes will lead to histotripsy emulsification of other collagenous tissues as well as clinical translation of tendon healing protocols, which has the potential to revolutionize treatment for rotator cuff tear and other collagenous tissue injuries.

项目摘要/摘要 高强度聚焦超声（HIFU）模式（例如组织疗法）已成功地用于 像心脏和肝脏一样乳化器官，但像肌腱一样高度胶原组织已证明具有抗性 用组织疗法进行机械乳化。最近，显示组织疗法会引发免疫反应 并释放生物标志物。如果组织疗法可以成功地乳化胶原组织，则具有潜力 通过诱发炎症并随后释放愈合因子来启动愈合反应。高 肌腱损伤的临床患病率，确定组织疗法是否可以在胶原层中产生微型塑料 促进愈合的肌腱有可能产生长期影响。 肩袖撕裂是肩痛的高度普遍原因，这就是患者寻求医疗治疗的原因。 手术修复是肩袖撕裂的常见治疗 机械加载肩袖在其双重作用中具有关节迁移率和稳定性。其他人有 使用的干点（DN），涉及重复用细规针刺穿肌腱以诱导 微型塑料和释放愈合因子，但是采用这种方法并不是广泛的。发展 可以非侵袭性促进愈合的技术，同时保持肌肉刺激的机械完整性 迫切需要单位。证明用于胶原组织乳化的组织疗法疗法将 提供临床上转移的工具，以立即补充当代的当前治疗选择 临床问题。 在这里，我们建议建立非侵入性组织疗法方案，以产生更好的肌腱指标 与DN相比，愈合，同时保持肌腱的机械性能。这些目标将是 完成：1）测试新型的组织练习方案以诱导胶原蛋白凝胶和离体大鼠中的微塑料 肌腱； 2）评估组织疗法和DN后肌腱的机械性能，并发展有限 评估参数并执行预测分析的元素模型； 3）确定是否组织疗法 在大鼠的试验性存活研究中，增强体内胶原组织愈合。这项创新的工作试图 证明组织疗法可以成功地乳状组织，并增强愈合的释放 因素。一旦证明了可行性，该项目中开发的方法和模型将是 缩放以检查大型动物模型和人类中的组织疗法。长期，结果将导致组织摄取 其他胶原组织的乳化以及肌腱愈合方案的临床翻译，这具有 彻底改变治疗肩袖撕裂和其他胶原组织损伤的潜力。