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

该PFI：AIR技术翻译项目专注于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）损伤或退变。 这些材料很重要，因为它们解决了临床问题（IVD变性），这是下背痛最常见的诊断，下背痛是一种影响15-30%美国人口的衰弱性疾病，相关的年成本为1000亿美元。该项目将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。纤维素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化，并允许掺入细胞和生长因子用于联合治疗。 与该市场领域正在开发的领先竞争材料相比，这些特征提供了广泛的安全性、成本效益、微创输送、增强的稳定性和治疗多功能性等优势。 该项目解决了几个技术差距，因为它从研究发现转化为IVD修复新材料的商业应用。 目前的手术治疗选择（即，椎间盘切除术）对于长期疾病管理是不够的，并且现有的商业植入物（即，全椎间盘置换）不能充分恢复椎间盘结构和功能。用可注射材料替换IVD的凝胶状髓核组织可能有助于恢复IVD的机械功能。有几种产品正在开发中，用于髓核置换，但没有一种产品被批准在美国使用。该项目的重点是使用可注射的纤维素基水凝胶，在椎间盘间隙原位形成，以取代切除的髓核组织。拟定的验证实验将表征优化的纤维素凝胶配方，该配方先前显示在轴向压缩下稳定并恢复椎间盘性能。 这些研究将确定小动物模型中的异物反应，以及使用大型动物脊柱运动节段损伤模型在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生物相容性差或表现出迁移和再疝。此外，很少有先前的研究能够在这种“最差情况”弯曲条件下评价候选材料。 因此，他们取得了有限的成功。此外，参与该项目的人员包括本科生和研究生，他们将通过转化医学课程接受创新和技术商业化方面的培训，并通过与潜在战略合作伙伴的定期互动，参加创新和商业化会议和研讨会，和小企业赠款提案准备。该项目聘请了西奈山伊坎医学院的整形外科专家和经验丰富的生物医学设备行业的专业人士分别指导生物力学评估研究和商业化方面，努力将所提出的技术从研究发现转化为商业现实。

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.