I-Corps: Stem cell-derived scaffolds for spinal fusion and maxillofacial bone repair

这个i-Corps项目的广泛影响/商业潜力涉及肌肉骨骼疾病和损伤的治疗，这是患者寻求医疗的最常见原因之一。这些手术源于创伤、先天缺陷、肿瘤切除和关节置换的治疗。骨折占这些疾病的大部分，有620万个骨折。然而，据估计，这些骨缺陷中高达10%与愈合不当有关。如果没有骨移植材料的帮助，这些缺陷会导致结构完整性降低，并可能导致截肢。治疗的黄金标准依赖于使用患者的骨骼作为移植。该项目正在开发的技术--来源于成骨干细胞的细胞外基质--提供了一种与患者的骨移植具有同等愈合性能的骨移植材料，而不存在与获取骨移植相关的潜在的慢性疼痛和感染风险。从科学的角度来看，这个项目代表着所有细胞衍生基质技术的颠覆性变化，因此有可能驱动基于组织工程的创新解决方案来再生其他组织。这个i-Corps项目旨在从培养的间充质干细胞(HMSCs)中产生一种成骨性骨移植材料。这项技术诱使hMSCs分化为一种中间的成骨表型，可用于产生细胞外基质，模仿成人胚胎骨骼发育和骨修复期间沉积的原始基质。从细胞中提纯后，该材料表现出显著的生物相容性，显著增加了植入的hMSCs的保留率，结合能力远远超过常用的骨替代材料。重要的是，这些特性加速了动物模型中的骨修复和脊柱融合。已经开发出从诱导性多能干细胞来源的hMSCs中生产和收获这种基质的方法，理论上可以无限扩增，因此现在有可能产生大量具有可靠特性的成骨基质。此外，这些细胞实际上能够产生比骨髓来源的hMSCs高得多的基质。这是一种平台技术，可以将这种基质与外科胶原海绵或其他合适的支架结合起来，作为目前使用的同种异体支架的替代品。

The broader impact/commercial potential of this I-Corps project addresses the treatment of musculoskeletal disease and injury, which are among the most common reasons patients seek medical treatment. These procedures arise from treatment of traumatic injury, congenital defects, tumor resection, and joint replacements. Bone fractures comprise a majority of these disorders with 6.2 million fractures. However, it is estimated that up to 10 percent of these bone defects are associated with improper healing. Without the aid of a bone graft material, these defects result in low structural integrity and potentially result in amputation. The gold standard of treatment relies on using bone from the patient as a graft. The technology under developed by this project, extracellular matrix derived from osteogenic stem cells, offers a bone graft material with equivalent healing properties to a patient's bone graft without the potential chronic pain and risk of infection associated with the harvesting a bone graft. From a scientific perspective, this project represents a disruptive change to all cell-derived matrix technologies, and as a result has the potential to drive innovative tissue engineering-based solutions to regenerate other tissues.This I-Corps project aims to generate an osteogenic bone graft material derived from cultured mesenchymal stem cells (hMSCs). The technology coaxes hMSCs to differentiate into an intermediate osteogenic phenotype that can be used generate extracellular matrix that mimics the primitive stroma deposited during embryological bone development and during bone repair in adults. When purified from the cells, this material exhibits remarkable biocompatibility and significantly increases retention of engrafted hMSCs, with far greater binding capacity than commonly employed bone substitutes. Importantly, these properties accelerate bone repair and spinal fusion in animal models. Methods have been developed to produce and harvest this matrix from hMSCs derived from induced pluripotent stem cells that can be theoretically expanded indefinitely, hence it is possible to now produce large amounts of osteogenic matrix with reliable properties. Further, these cells are actually able to produce matrix in much higher quantities than that produced by bone marrow-derived hMSCs. This is a platform technology to harvest and combine this matrix with surgical collagen sponge or other suitable scaffolds as a replacement for currently used allogenic scaffolds.