Nanofibrous Hollow Microspheres for Bone Regeneration

描述(申请人提供)：在临床上，经常有不规则形状的缺陷和伤口需要填充和修复。在这种情况下，使用可注射支架的前景非常有吸引力，因为它们可以很容易地以微创的方式原位填充不规则形状的缺陷。额外的好处是恢复迅速，并提高了患者的舒适性和满意度。然而，目前的可注射生物材料在临床应用中存在着各种限制。我们最近建立了一种设计、合成和制造纳米纤维中空微球(NF-HMS)的策略，作为组织再生的新型可注射细胞载体。核因子-HMS完全由胶原样纳米纤维组成，具有开放的中空结构，旨在促进细胞的迁移、增殖 和组织再生。结果表明，核因子-HMS是一种良好的组织再生可注射性生物材料。在目前的应用中，我们建议将生物活性物质(生长因子)引入到核因子-HMS中，并开发一种分级的自组装可注射支架系统用于骨再生。在这个系统中，生物活性物质将被包裹在可生物降解的纳米球中，这些纳米球被固定在核因子-HMS中。在植入缺损区之前，细胞会在核因子-HMS的表面和内部黏附、增殖和迁移。纳米球中的生物活性物质将以一种精确控制的方式释放(由纳米球和核因子-HMS共同控制)，以诱导细胞分化和新组织的形成。我们的中心假设是，这种独特的可注射系统将为组织再生提供一个优越的环境。本研究的具体目标如下：1)发展可注射的BMP2可控递送的层次型核因子-HMS支架系统。2)检测该支架系统作为骨组织再生的可注射性载体。我们的长期目标是探索和扩展层次化的核因子-HMS支架系统，以应用于广泛的生物医学领域。我们预计，拟议的研究结果将极大地扩展我们的模式，设计合适的支架系统，导致新的先进的再生疗法。

DESCRIPTION (provided by applicant): In clinics, there are often defects and wounds of irregular shapes that need to be filled and repaired. In such cases, the prospects of using injectable scaffolds are very attractive because they can easily fill irregular- shaped defects in situ in a minimally invasive manner. Added benefits are a rapid recovery and improved comfort and satisfaction for the patients. However, current injectable biomaterials have various limitations to clinical applications. We have recently established a strategy to design, synthesize, and fabricate nanofibrous hollow microspheres (NF-HMS) as novel injectable cell carriers for tissue regeneration. NF-HMS are composed entirely of collagen-like nanofibers and have an open and hollow structure purposefully designed to facilitate cell migration, proliferation and tissue regeneration. Our results have indicated that NF-HMS are an excellent injectable biomaterials for tissue regeneration. In the current application, we propose to incorporate bioactive agents (growth factors) into NF-HMS and develop a hierarchical self-assembled injectable scaffolding system for bone regeneration. In this system, bioactive agents will be encapsulated into the biodegradable nanospheres, which are immobilized in the NF-HMS. Cells will adhere, proliferate and migrate on the surface and the inside of the NF-HMS before being injected into defects. Bioactive agents in the nanospheres will be released in a precisely controlled way (by both nanospheres and NF-HMS) to induce cell differentiation and new tissue formation. Our central hypothesis is that this unique injectable system will provide a superior environment for tissue regeneration. For this study, the following specific aims are proposed: 1) To develop injectable hierarchical NF-HMS scaffolding systems with controlled delivery of BMP2. 2) To test this scaffolding system as a promising injectable carrier for bone tissue regeneration. Our long-term goal is to explore and expand the hierarchical NF-HMS scaffolding system to a broad spectrum of biomedical applications. We expect that the outcomes of the proposed research will greatly expand our modality to design a suitable scaffolding system, leading to new advanced regenerative therapies.