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

项目总结/摘要 简介：Skeleton组织工程实验室（STEL）技术有限责任公司是一家女性拥有的密歇根州- 再生医学公司成立于2013年。STEL的第一个产品CGEM ™移植物是一种独特的 前交叉韧带（ACL）损伤的生物替代。研究人员已经对此进行了调整， 移植技术的目的是治疗肩袖（RC）损伤日益普遍的老龄人口。 意义：在美国，RC撕裂是一个主要的骨科挑战，进行了超过460，000例手术 每年的市场成本超过5.23亿美元[1，46]。目前钢筋混凝土修复程序的失败率范围 从20- 95%，一个主要的影响因素是无法恢复天然的生物力学性能， 附着点，导致修复，其特征在于更弱，组织更少的纤维血管瘢痕组织， 失败[54]。正在开发各种组织工程策略以改善手术结果并促进 肌腱愈合，特别是在附着点。目前的方法侧重于开发生物或 合成支架装置，以加强肌腱-骨连接的机械强度，但它们不 促进附着点再生。对钢筋混凝土维修的替代技术有很大的需求。 商业产品愿景：ETG-RC是灭活同种异体工程化多相组织， 再生附着点并提供允许内源性细胞迁移的基底， 修复部位的再生能力。ETG-RC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。一种“现成的”组织移植物， RC修复将提高双排缝合技术的护理标准，并提供上级患者结局。 建议的研究目标：这个SBIR项目的目标是建立一个完整的制造的可行性， 生物“现成的”组织工程肩袖肌腱移植物，可以恢复生物力学性能， 肌腱-肱骨附着点;并降低ETG-RC的商业可行性风险，以促进 该技术用于人类患者的可转化性。 具体目标：拟议的项目解决了几个紧迫的问题，必须解决之前， 将这项技术提交给FDA进行临床试验：开发制造和脱细胞方案 (Aim 1）和建立储存方法，以确定有效期（目的2）。然后，它试图建立一个主 用于制造1-3期临床试验（Aim 3）移植物的细胞库。制造CGMP优质ETG-RC移植物 将由NAMSA对已建立的主细胞库中的细胞进行安全性和有效性试验（目标4）。正数据 这些研究将支持向FDA提交IND数据包，从而能够进行I期临床试验。成功 SBIR项目将导致开发一种“现成的”肌腱移植物，用于第一次人体I期试验 临床试验这是一个重要的商业化里程碑，也是 治疗软组织骨科损伤。

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.