Injectable and Strong Nano-Apatite/Stem Cell Scaffolds for Bone Regeneration

描述（由申请人提供）：美国每年有700万人患有骨折，肌肉骨骼疾病每年花费2150亿美元。随着人口老龄化，这些数字正在急剧增加。磷酸钙骨水泥（CPC）可以在原位成型和固化形成羟基磷灰石，具有骨导电性，并且可以被新骨吸收和替换。然而，CPC的低强度限制了其在非应力位置的使用。母赠款研究成分和微观结构的剪裁，以提高注射性，强度和再吸收；优化壳聚糖含量；开发高应变、抗冲刷的非刚性CPC；将生长因子释放模型建立为孔隙体积分数和时间的函数；进行CPC吸收及微结构设计影响的动物实验，以及骨再生及单、多生长因子及MSCs输送作用的动物实验。然而，父母资助不包括使用电纺丝纳米纤维，也不包括人类脐带间充质干细胞（hUCMSCs）。这一竞争性修订补充的目标是：(1)开发新型的可注射纳米纤维cpc支架，具有更高的承重能力和增强的干细胞附着和骨修复功能；(2)建立纳米纤维与支架性能、纳米纤维与干细胞附着、增殖、分化和体内骨再生之间的关系；(3)确定通过纳米纤维- cpc支架递送的hUCMSCs在骨再生方面是否比成人骨髓来源的hMSCs更优越。目标1将开发电纺丝纳米纤维cpc作为可注射、承重和生物活性的支架。目的2研究纳米纤维- cpc支架对hMSC和hUMCSC增殖分化的影响。目的3将研究纳米纤维- cpc递送hMSC和hUCMSC对动物骨再生的影响。该项目预计将首次证明，通过新型纳米纤维cpc支架递送的hUCMSCs在成骨和骨再生方面比骨髓来源的hMSCs更优越。这些发现可能会对基于干细胞的组织工程和未来的临床治疗产生重大影响。具有干细胞和生长因子输送的新型可注射、强强度和大孔纳米纤维cpc支架有望广泛应用于牙科、颅面和骨科，极大地增强骨再生，改善数百万人的健康和生活质量。

DESCRIPTION (provided by applicant): Seven million people suffer bone fractures annually in the U.S. Musculoskeletal conditions cost $215 billion/year. These numbers are increasing dramatically as the population ages. Calcium phosphate cement (CPC) can be molded and set in-situ to form hydroxyapatite, is osteoconductive, and can be resorbed and replaced by new bone. However, the low strength of CPC limits its use to non-stress locations. The parent grant investigates compositional and microstructural tailoring to improve injectability, strength and resorption; optimizes chitosan content; develops non-rigid CPC with high-strain and anti-washout; models growth factor release as a function of pore volume fraction and time; and performs animal study on CPC resorption and the effects of microstructural design, and animal study on bone regeneration and the effects of single and multiple growth factors and MSCs delivered. However, the parent grant does not include the use of electrospun nanofibers, nor human umbilical cord mesenchymal stem cells (hUCMSCs). The objectives of this competitive revision supplement are to: (1) Develop novel, injectable nanofiber-CPC scaffolds with increased load-bearing capability and enhanced stem cell attachment and function for bone repair; (2) establish relationships between nanofibers and scaffold properties, and between nanofibers and stem cell attachment, proliferation, differentiation, and in vivo bone regeneration; (3) determine whether hUCMSCs are more superior than adult bone marrow-derived hMSCs in bone regeneration, when delivered via nanofiber-CPC scaffold. Aim 1 will develop electrospun nanofiber-CPC as injectable, load-bearing, and bioactive scaffold. Aim 2 will study the effect of nanofiber-CPC scaffold on hMSC and hUMCSC proliferation and differentiation. Aim 3 will investigate the effects of hMSC and hUCMSC delivery via nanofiber-CPC on bone regeneration in animal model. This project is expected to demonstrate, for the first time, that hUCMSCs delivered via novel nanofiber-CPC scaffold are more superior in osteogenesis and bone regeneration, than bone marrow-derived hMSCs. These findings will potentially have a highly significant impact on stem cell-based tissue engineering and future clinical treatments. The new injectable, strong and macroporous nanofiber-CPC scaffolds with stem cell and growth factor delivery are expected to have a wide range of dental, craniofacial and orthopedic applications, with greatly enhanced bone regeneration to improve the health and quality of life for millions of people. PUBLIC HEALTH RELEVANCE: This project will develop the first injectable, moderate load-bearing, macroporous, bone-mimicking nanofiber-apatite scaffolds with stem cell and multiple growth factor delivery, and will study bone regeneration in animal model. Potential applications include dental, craniofacial and orthopedic repairs. They include maxillofacial reconstruction using the moldable scaffold to achieve shaping and esthetics, and minimally-invasive surgeries such as filling and strengthening osteoporotic bone lesions at risk for fracture, with greatly enhanced bone healing and regeneration to improve the health and quality of life for millions of people.