Development of a Novel Engineered Tendon Graft to Assist in Repair of Rotator Cuff Injuries

开发新型工程肌腱移植物以协助修复肩袖损伤

• 批准号: 10697147
• 负责人: Thomas Bollenbach
• 金额: $ 94.33万
• 依托单位: PRO THERAPEUTICS LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697147
• 关键词: Address; Allogenic; Animals; Arthritis; Biological; Biomechanics; Capital; Cells; Characteristics; Cicatrix; Clinic; Clinical; Clinical Trials; Collagen; Communities; DNA; Data; Development; Devices; Engineering; Failure; Fibrocartilages; Funding; Goals; Histologic; Histology; Human; Injury; Investments; Laboratories; Life; Marketing; Mechanics; Methodology; Methods; Michigan; Modulus; Natural regeneration; Operative Surgical Procedures; Orthopedics; Outcome; Patient-Focused Outcomes; Patients; Phase; Phase I Clinical Trials; Physiological; Procedures; Production; Property; Protocols documentation; Qualifying; Recovery; Regenerative Medicine; Regenerative capacity; Research; Research Personnel; Risk; Rotator Cuff; Sheep; Site; Small Business Innovation Research Grant; Source; Sterility; Surgical sutures; Suture Techniques; Techniques; Technology; Tendon Injuries; Tendon structure; Testing; Tissue Engineering; Tissue Grafts; Tissues; Toxicology; Translations; United States; Vision; Woman; Work; aging population; anterior cruciate ligament injury; biological development; biomaterial compatibility; bone; bone marrow mesenchymal stem cell; cell bank; commercialization; cost; design; fabrication; first-in-human; healing; humerus; improved; in vivo; innovation; laboratory equipment; manufacture; mechanical signal; migration; mineralization; novel; protein structure; repair strategy; repaired; restoration; rotator cuff injury; rotator cuff tear; safety testing; scaffold; skeletal tissue; soft tissue; standard of care; success; surgery outcome; tendon graft; tissue regeneration

PROJECT SUMMARY/ABSTRACT Introduction: Skeletal Tissue Engineering Laboratories (STEL) Technologies, LLC is a woman-owned, Michigan- based regenerative medicine company founded in 2013. STEL’s first product, the CGEMTM graft, is a unique biological replacement for the anterior cruciate ligament (ACL) injuries. The researchers have since adapted this graft technology with the goal of treating Rotator Cuff (RC) injuries increasingly prevalent in the aging population. Significance: RC tears are a major orthopedic challenge in the US with over 460,000 surgeries performed annually resulting in a market cost of over $523M[1,46]. The failure rate of current RC repair procedures ranges from 20-95%, with a major contributing factor being the inability to restore native biomechanical properties at the enthesis, resulting in repairs characterized by a weaker, less organized fibrovascular scar tissue that is prone to failure[54]. Various tissue-engineering strategies are being developed to improve surgical outcomes and promote tendon healing, especially at the enthesis. Current approaches focus on the development of biological or synthetic scaffold devices to reinforce the mechanical strength of the tendon-to-bone connection, but they do not promote enthesis regeneration. There is significant demand for alternative technologies for RC repair. Vision for Commercial Product: The ETG-RC is devitalized allogeneic engineered multi-phasic tissue that regenerates the enthesis and provide an underlayment that allows the migration of endogenous cells, enhancing the regenerative capacity of the repair site. ETG-RC will lead to enhanced restoration of normal biomechanics and mobility, resulting in lower cost and decreased risk of re-injury and arthritis. An “off-the-shelf” tissue graft for RC repair will enhance the standard of care double row suture technique and deliver superior patient outcomes. Goals of Proposed Research: The goals of this SBIR Project are to establish the feasibility of fabricating a fully biologic “off-the-shelf” tissue-engineered rotator cuff tendon graft that can restore biomechanical properties of the tendon-humerus enthesis; and to de-risk the commercial viability of ETG-RC in order to advance the translatability of this technology for use in human patients. Specific Aims: The proposed project addresses the several pressing issues that must be resolved prior to bringing this technology to the FDA for clinical trials: development of a fabrication and decellularization protocol (Aim 1) and establishment of storage methods to determine shelf life (Aim 2). It then seeks to establish a master cell bank for fabrication of grafts for the Phase 1-3 clinical trials (Aim 3). CGMP quality ETG-RC grafts fabricated from the established master cell bank will be tested for safety and efficacy by NAMSA (Aim 4). Positive data from these studies will support filing of an IND-packet with FDA, enabling a Phase I clinical trial. Success of the SBIR project will result in the development of an “off-the-shelf” tendon graft ready for first-in-human Phase I clinical trials. This represents a significant commercialization milestone and a transformative innovation for the treatment of soft tissue orthopedic injuries.

项目概要/摘要 简介：骨骼组织工程实验室 (STEL) Technologies, LLC 是一家女性所有的密歇根州公司 总部位于再生医学公司，成立于 2013 年。STEL 的第一个产品 CGEMTM 移植物是一种独特的 此后，研究人员对前十字韧带（ACL）损伤进行了生物替代。 移植技术的目标是治疗在老龄化人口中日益普遍的肩袖 (RC) 损伤。 意义：在美国，RC 撕裂是一项重大的骨科挑战，已进行了超过 460,000 例手术 每年导致市场成本超过 5.23 亿美元[1,46] 当前 RC 维修程序的故障率不等。 20-95%，主要影响因素是无法恢复原生生物力学特性 附着点，导致修复的特点是较弱、组织较少的纤维血管疤痕组织，容易发生 正在开发各种组织工程策略来改善手术结果并促进 肌腱愈合，尤其是在附着点处，目前的方法侧重于生物或肌腱的发展。 合成支架装置可以增强肌腱与骨骼连接的机械强度，但它们并不 促进附着点再生对 RC 修复的替代技术有很大的需求。 商业产品愿景：ETG-RC 是充满活力的同种异体工程多相组织， 再生附着点并提供允许内源细胞迁移的底层，增强 ETG-RC 的再生能力将增强正常生物力学的恢复。 和灵活性，从而降低成本并降低再次受伤和关节炎的风险。 RC 修复将提高双排缝合技术的护理标准并提供卓越的患者治疗效果。 拟议研究的目标：该 SBIR 项目的目标是确定制造完全的可行性 生物“现成的”组织工程肩袖肌腱移植物，可以恢复肩袖肌腱的生物力学特性 肌腱-肱骨附着点；并降低 ETG-RC 的商业可行性风险，以推进 该技术在人类患者中使用的可转化性。 具体目标：拟议的项目解决了在实施之前必须解决的几个紧迫问题 将该技术带到 FDA 进行临床试验：开发制造和脱细胞方案 （目标 1）并建立确定保质期的储存方法（目标 2）。 用于为 1-3 期临床试验（目标 3）制造移植物的细胞库。 来自已建立的主细胞库的安全性和有效性将由 NAMSA 进行测试（目标 4）。 这些研究成果将支持向 FDA 提交 IND 数据包，从而使 I 期临床试验取得成功。 SBIR 项目将开发出一种“现成的”肌腱移植物，为首次人体第一阶段做好准备 这代表了一个重要的商业化里程碑和变革性创新。 软组织骨科损伤的治疗。