Nanofibrous Hollow Microspheres for Bone Regeneration

描述（申请人提供）：临床上经常有形状不规则的缺损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损。额外的好处是快速恢复和改善患者的舒适度和满意度。然而，目前的可注射生物材料在临床应用中存在各种局限性。我们最近建立了一个策略，设计，合成和制造纳米纤维空心微球（NF-HMS）作为新的可注射细胞载体的组织再生。NF-HMS完全由胶原样纳米纤维组成，具有开放和中空的结构，旨在促进细胞迁移、增殖 和组织再生。结果表明，NF-HMS是一种优良的可注射性组织再生生物材料。在当前的应用中，我们建议将生物活性剂（生长因子）纳入NF-HMS，并开发一种用于骨再生的分级自组装可注射支架系统。在该系统中，生物活性剂将被封装到可生物降解的纳米球中，该纳米球被固定在NF-HMS中。细胞在注入缺损之前会在NF-HMS的表面和内部粘附、增殖和迁移。纳米球中的生物活性剂将以精确控制的方式（通过纳米球和NF-HMS）释放，以诱导细胞分化和新组织形成。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上级环境。对于本研究，提出了以下具体目标：1）开发具有BMP 2的受控递送的可注射分级NF-HMS支架系统。2)以测试这种支架系统作为骨组织再生的有前途的可注射载体。我们的长期目标是探索和扩展层次NF-HMS支架系统，以广泛的生物医学应用。我们预计，拟议研究的结果将大大扩展我们的模式，以设计一个合适的支架系统，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.