PFI:AIR-TT: Biocompatibility and Biomechanical Validation of Cellulose-Based Hydrogels for Intervertebral Disc Repair

PFI:AIR-TT：用于椎间盘修复的纤维素基水凝胶的生物相容性和生物力学验证

基本信息

批准号：
1701120
负责人：
Steven Nicoll
金额：
$ 20万
依托单位：
CUNY City College
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2019-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1701120&HistoricalAwards=false
关键词：
PFI AIR TT Biocompatibility Biomechanical

项目摘要

This PFI: AIR Technology Translation project focuses on translating a novel injectable biomaterial derived from the plant polysaccharide, cellulose, to treat injuries or degeneration of the intervertebral disc (IVD). These materials are important because they address a clinical problem (IVD degeneration) that is the most common diagnosis for lower back pain, a debilitating condition that affects 15-30% of the United States population, with associated annual costs of $100 billion. The project will result in valuable proof-of-concept data demonstrating safety and efficacy of these cellulosic biomaterials in a small animal in vivo model and a large animal explant model. Successful completion will motivate further validation in a large animal preclinical injury model prior to clinical studies. The cellulosic materials are unique in that they are plant-derived, gel in situ via a dual coupling mechanism and allow for the incorporation of cells and growth factors for combination therapies. These features provide the advantages of an extensive safety profile, cost effectiveness, minimally invasive delivery, enhanced stability and therapeutic versatility when compared to the leading competing materials under development in this market space. This project addresses several technology gaps as it translates from research discovery toward commercial application of a novel material for IVD repair. Current surgical treatment options (i.e., discectomy) are inadequate for long-term disease management, and existing commercial implants (i.e., total disc replacement) do not sufficiently restore disc structure and function. Replacing the gelatinous nucleus pulposus tissue of the IVD with an injectable material may help restore IVD mechanical functionality. Several products are under development for nucleus pulposus replacement, with none approved for use in the United States. This project focuses on the use of injectable cellulose-based hydrogels that form in situ in the intradiscal space to replace resected nucleus pulposus tissue. The proposed validation experiments will characterize an optimized cellulosic gel formulation previously shown to be stable and restore disc properties under axial compression. The studies will determine the foreign body reaction in a small animal model as well as the mechanical properties and failure mechanisms under cyclic loading in bending using a large animal spine motion segment injury model. Many of the competing products under development have been found to have poor biocompatibility or exhibited migration and reherniation. Also, few prior studies have been capable of evaluating candidate materials under such "worst-case-scenario" bending conditions. As such, they have met with limited success. In addition, personnel involved in this project include undergraduate and graduate students who will receive training in innovation and technology commercialization through translational medicine courses, and via regular interactions with potential strategic partners, participation in innovation and commercialization conferences and symposia, and small business grant proposal preparation.The project engages experts in orthopaedic surgery from the Icahn School of Medicine at Mount Sinai and an experienced biomedical device industry professional to guide the biomechanical evaluation studies and commercialization aspects, respectively, in this effort to translate the proposed technology from research discovery toward commercial reality.

该 PFI：AIR 技术翻译项目的重点是翻译一种源自植物多糖、纤维素的新型可注射生物材料，用于治疗椎间盘 (IVD) 损伤或退化。这些材料很重要，因为它们解决了以下临床问题（IVD 退化）：是腰痛最常见的诊断，腰痛是一种使人衰弱的疾病，影响着 15-30% 的美国人口，每年相关费用将达到 1000 亿美元。产生有价值的概念验证数据，证明这些纤维素生物材料在小动物体内模型和大型动物外植体模型中的安全性和有效性。成功完成将激励在临床研究之前在大型动物临床前损伤模型中进行进一步验证。该材料的独特之处在于它们是植物来源的，通过双重偶联机制原位凝胶，并允许掺入细胞和生长因子进行联合治疗。这些特性提供了广泛的安全性、成本效益和最低限度的优势。与该市场领域正在开发的领先竞争材料相比，该项目具有侵入性输送、增强的稳定性和治疗多功能性，因为它将用于 IVD 修复的新型材料的研究发现转化为商业应用。椎间盘切除术（即椎间盘切除术）不足以进行长期疾病管理，并且现有的商业植入物（即全椎间盘置换术）不能充分恢复椎间盘结构和功能。可注射材料可能有助于恢复 IVD 机械性能。目前正在开发几种用于髓核置换的产品，但尚未批准在美国使用。该项目的重点是使用在椎间盘内原位形成的可注射纤维素水凝胶。所提出的验证实验将表征一种优化的纤维素凝胶配方，该配方先前已被证明是稳定的并在轴向压缩下恢复椎间盘特性，以及确定小动物模型中的异物反应。使用大型动物脊柱运动节段损伤模型研究弯曲循环载荷下的机械性能和失效机制，许多正在开发的竞争产品被发现具有较差的生物相容性或表现出迁移和再突出。在这种“最坏情况”弯曲条件下评估候选材料因此，他们取得的成功有限。此外，参与该项目的人员包括将通过转化医学接受创新和技术商业化培训的本科生和研究生。课程，并通过定期互动与潜在的战略合作伙伴合作，参与创新和商业化会议和研讨会，以及小企业拨款提案的准备。聘请西奈山伊坎医学院的骨科手术项目专家和经验丰富的生物医疗器械行业专业人士来指导生物力学评估研究分别在和商业化方面，努力将所提出的技术从研究发现转化为商业现实。