SBIR Phase I: An Injectable Treatment for the Repair of Damaged Tendons and Ligaments

SBIR 第一阶段：修复受损肌腱和韧带的注射治疗

• 批准号: 2026007
• 负责人: Adam Hacking
• 金额: $ 25.59万
• 依托单位: RegenX LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2026007&HistoricalAwards=false
• 关键词: SBIR; Phase; Injectable; Treatment; Repair

The broader impact of this Small Business Innovation Research (SBIR) Phase I project will be improvement of quality of life and reduction of healthcare costs associated with tendon and ligament injuries which are notoriously difficult and slow to heal, depriving millions of Americans years of productivity. Tendon and ligament injuries are especially debilitating for the aged, the active or those with physically demanding professions. Injured ligaments (e.g. anterior cruciate ligament) or tendons (e.g. Achilles) require months of rehabilitation and can take up to a year to heal. In the elderly, rotator cuff injuries are pernicious, prevalent and refractory to treatment. Every year in the US, $130 billion is spent on musculoskeletal injury-related medical visits, 60% of which are tendon and ligament injuries. Tendon and ligament injuries result in 288 million lost work days costing the US economy $50 billion annually. In spite of decades of effort, there has been very little improvement in either the rate or the quality of healing for these injuries. The injectable repair system proposed could reduce healing time and improve repair quality. The proposed plan to drastically reduce the cost of the raw materials through human cell engineering will make the treatment solution universally affordable.The proposed project will determine the feasibility of an entirely new approach to tendon and ligament repair based upon the in vivo delivery and assembly of collagen monomers into the path of force. The approach is derivative of two recent innovations that will be combined in four objectives to produce an injectable collagen-based solution designed to accelerate the repair of damaged connective tissues (i.e. ligaments and tendons) the healing of which presents a significant medical challenge. The first innovation is the use of CRISPR/CAS9 technology which will be used to accelerate the production of collagen by human fibroblasts. Objective 1 will to optimize the CRISPR process and scale it up through isolation and expansion of cells receptive to enhanced collagen production. Objective 2 will leverage the second major innovation, liquid crystal collagen processing technology, to develop a shelf stable injectable solution of highly-dense particulates that is expected to donate large amounts of collagen to injured connective tissue. Objective 3 will demonstrate that the injectable repair solution will deliver collagen to repair damage in vitro and Objective 4 will apply the approach in vivo, to demonstrate that exogenous collagen delivery can speed the repair of damaged, living tendon.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项小型企业创新研究（SBIR）第一阶段项目的更广泛影响将是改善生活质量，降低与肌腱和韧带损伤相关的医疗费用，这些损伤是出了名的困难和缓慢愈合，剥夺了数百万美国人多年的生产力。肌腱和韧带损伤对老年人、活跃人士或从事体力要求高的职业的人来说尤其严重。受伤的韧带（如前十字韧带）或肌腱（如跟腱）需要数月的康复，可能需要长达一年的时间才能愈合。在老年人中，肩袖损伤是有害的，普遍的和难治的。在美国，每年花费1300亿美元用于肌肉骨骼损伤相关的医疗就诊，其中60%是肌腱和韧带损伤。肌腱和韧带损伤导致2.88亿个工作日的损失，每年给美国经济造成500亿美元的损失。尽管经过几十年的努力，这些损伤的愈合速度或质量都没有多大改善。提出的可注射修复系统可以缩短愈合时间，提高修复质量。通过人体细胞工程大幅降低原材料成本的计划将使治疗方案普遍负担得起。该计划将确定一种全新的肌腱和韧带修复方法的可行性，该方法基于体内胶原蛋白单体的输送和组装到力的路径中。该方法是最近两项创新的衍生物，将在四个目标中结合，以产生一种基于胶原蛋白的可注射溶液，旨在加速受损结缔组织（即韧带和肌腱）的修复，其愈合提出了重大的医学挑战。第一项创新是使用CRISPR/CAS9技术，该技术将用于加速人类成纤维细胞生产胶原蛋白。目标1将优化CRISPR过程，并通过分离和扩增接受增强胶原蛋白生产的细胞来扩大规模。目标2将利用第二项重大创新，即液晶胶原蛋白加工技术，开发一种储存稳定的高密度颗粒注射液，有望为受损结缔组织提供大量胶原蛋白。目标3将证明可注射修复溶液将提供胶原蛋白以修复体外损伤，目标4将在体内应用该方法，以证明外源性胶原蛋白递送可以加速受损的活肌腱的修复。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。