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.

生物制造肩袖肌腱止点植入物的临床前评价 再生 项目总结/摘要 肩袖损伤是一个主要的临床问题，导致250，000例肩袖修复手术（RCR） 仅在美国每年进行的手术。报告了RCR后的再破裂率 在目前的护理标准下，超过95%。满足改善旋转器的临床需求 肩袖愈合，本研究的目标是优化生物制造，保存和体内 用于肌腱的生物增强型组织工程器械（Bio-TEND）的性能， 肌腱-骨（附着点）再生。在多项专利的支持下，Bio-TEND是：1.）一口井 由良性溶剂电纺的特征化的、各向异性的、可再吸收的胶原微纤维移植物; 2.）的情况。工程化用于高空隙以促进快速细胞向内生长和重塑;以及3.） 用临床级干细胞生物制造，为肌腱和纤维软骨形成做好准备， 促进附着点再生。我们的假设是Bio-TEND移植物会加速 产生新的、宿主产生的、致密的、规则定向的肌腱样组织和附着点 在RCR模型中集成。我们将实现两个必要的具体目标， FDA的批准和商业化。目标1：建立最佳的生物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 我们SBIR第一阶段工作的完成将产生RCR治疗剂的生物制造，包括 扩大规模、保存和性能研究。这项工作将导致大型动物的关键测试 和SBIR II期的作用机制研究，以及III期的人体临床试验。结果 这些SBIR研究将为FDA提交和成功上市提供所需的数据， 产品该项目汇集了具有必要的补充专门知识的调查人员， 医疗器械和细胞疗法的翻译（弗朗西斯博士，Embody）和肌腱生物学， RCR的生物力学和动物模型（宾夕法尼亚州的Soslowsky博士），与世界一流的 外科医生来开发这种关键的治疗方法。