Preclinical Evaluation of a Biofabricated Implant for Rotator Cuff Tendon-Enthesis Regeneration

用于肩袖肌腱附着点再生的生物制造植入物的临床前评估

• 批准号: 9907884
• 负责人: Michael Paul Francis
• 金额: $ 22.39万
• 依托单位: EMBODY, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9907884
• 关键词: Address; Air; Animal Model; Animals; BMP-12; Benign; Biocompatible Materials; Biological; Biology; Biomanufacturing; Biomechanics; Bone Marrow; Cadaver; Cells; Chronic; Clinical; Clinical Trials; Collagen; Cryopreservation; Cyclic GMP; Data; Defect; Dermis; Development; Devices; Engineering; Evaluation; Fibrocartilages; Goals; Health; Histology; Human; Implant; Legal patent; Letters; Light; Mechanics; Medical Device; Mesenchymal Stem Cells; Metabolic; Methodology; Modeling; Musculoskeletal; Natural regeneration; Operative Surgical Procedures; Outcome; Patients; Performance; Phase; Polarization Microscopy; Polymers; Population; Procedures; Production; Rattus; Regenerative Medicine; Reporting; Research; Research Personnel; Rotator Cuff; Route; Rupture; Shoulder; Small Business Innovation Research Grant; Solvents; Source; Stem cells; Surgeon; Technology; Tendon structure; Testing; Therapeutic; Tissue Engineering; Tissues; Translations; Tube; Work; base; biomechanical model; bone; clinical translation; commercialization; design; dosage; healing; implantation; improved; in vivo; in vivo evaluation; innovation; meetings; novel; off-patent; preclinical evaluation; preclinical study; preservation; regenerative; relative effectiveness; repaired; research and development; rotator cuff injury; scale up; standard of care; tissue regeneration

Preclinical Evaluation of a Biofabricated Implant for Rotator Cuff Tendon-Enthesis Regeneration Project Summary/Abstract Rotator cuff injuries are a major clinical problem, leading to 250,000 surgical rotator cuff repair (RCR) procedures performed annually in the U.S. alone. Re-rupture rates following RCR are reported upwards of 95% with the current standard of care. Addressing the clinical need for improving rotator cuff healing, the goals of this research are to optimize the biomanufacturing, preservation and in vivo performance of a Biologically-enhanced Tissue ENgineered Device (Bio-TEND) for tendon and tendon-to-bone (enthesis) regeneration. Supported by multiple patents, Bio-TEND is: 1.) a well- characterized, anisotropic, resorbable collagen microfibrous graft electrospun from a benign solvent; 2.) engineered for high void to promote rapid cellular ingrowth and remodeling; and 3.) biomanufactured with clinical grade stem cells primed for tendon and fibrocartilage formation to promote enthesis regeneration. Our hypothesis is that Bio-TEND grafts will accelerate the production of new, host-generated, dense, regularly oriented tendon-like tissue and enthesis integration in a RCR model. We will accomplish two specific aims necessary for progressing through FDA approval and to commercialization. Aim 1: Establish Optimal Bio-TEND Biomanufacturing and Preservation Strategies. Aim 2: Assess Bio-TEND in a Chronic Rat RCR Model. Successful completion of our SBIR Phase I work will yield biomanufacturing of a therapeutic for RCR, including scale up, preservation and performance studies. This work will lead to pivotal testing in large animals and Mechanism of Action studies in SBIR Phase II, and human clinical trials in Phase III. Results of these SBIR studies will provide the data required for FDA submission and to successfully market the product. This project brings together investigators with the necessary complementary expertise in the translation of medical devices and cellular therapies (Dr. Francis, Embody), and tendon biology, biomechanics and animal models for RCR (Dr. Soslowsky, Penn), working together with world-class surgeons to develop this critical therapeutic.

生物修复肩袖肌腱植入物的临床前评价 再生 项目摘要/摘要 肩袖损伤是一个主要的临床问题，导致25万例肩袖修复手术(RCR) 每年仅在美国进行一次手术。RCR术后再破裂率的报道 在目前的护理标准下，95%以上。满足临床对改善旋转器的需求 袖带愈合，这项研究的目标是优化生物制造，保存和体内 生物增强型肌腱组织工程化装置(Bio-Tend)的性能研究 肌腱到骨(末端)再生。由多项专利支持的Bio-Tend是：1)一口井- 表征，各向异性，可吸收的胶原微纤维从良性溶剂电纺接枝； 2.)设计用于高空隙以促进细胞快速向内生长和重塑；以及3) 临床级干细胞用于肌腱和纤维软骨形成的生物制造 促进凹陷再生。我们的假设是Bio-Tend移植物将加速 生产新的、宿主产生的、致密的、规则定向的肌腱样组织和末端 RCR模型中的集成。我们将实现取得进展所必需的两个具体目标 FDA的批准和商业化。目标1：建立最佳的Bio-Tend生物制造和 保存策略。目的2：在慢性大鼠RCR模型中评估Bio-Tend。成功 完成我们的SBIR第一阶段工作将产生一种RCR治疗药物的生物制造，包括 扩展、保存和性能研究。这项工作将导致在大型动物身上进行关键的测试 和SBIR第二阶段的作用机制研究，以及第三阶段的人体临床试验。 这些SBIR研究将提供FDA提交所需的数据，并成功将 产品。该项目汇集了具有必要的补充专业知识的调查人员 翻译医疗器械和细胞疗法(弗朗西斯博士，具体化)，肌腱生物学， RCR的生物力学和动物模型(宾夕法尼亚州索斯洛夫斯基博士)，与世界级的 外科医生来开发这种关键的治疗方法。