BMSCs构建的软骨在皮下环境中表型易于丧失阻碍了其临床应用，究其原因主要与构建过程中BMSCs软骨的肥大化及皮下移植后的血管化有关。我们前期研究证实FAK在BMSCs软骨肥大化及血管化中发挥了重要作用。基于此，本项目提出以下科学假说：将一种新型的FAK抑制剂Defactinib载入电纺明胶-聚己内酯(Gt-PCL)纳米纤维中，从而形成一个抑制肥大化和血管化的构建微环境，最终维持皮下BMSCs软骨的表型稳定。为此，本项目将开展以下研究内容：1.Defactinib-Gt-PCL载药材料的制备与鉴定；2.载药材料对BMSCs软骨体外肥大化的影响；3.载药材料对BMSCs软骨皮下血管化的影响；4.载药材料在维持BMSCs软骨表型稳定中的作用机制研究。该项目的成功将为基于BMSCs的软骨组织工程提供了新的理论基础和构建策略。

The currently BMSCs-engineered cartilage is unsatisfactory for clinical application due to unstable phenotype in the subcutaneous environment, this phenomenon mainly results from hypertrophic differentiation of chondrocytes induced from BMSCs cultured in vitro and vascularization subcutaneously. Our previous studies indicate that FAK play an important role in hypertrophy and vascularization of BMSCs-engineered cartilage. Based on this, a scientific hypothesis is presented out: an electrsopun gelatin-PCL (Gt-PCL) nanofibrous scaffold loaded with a novel FAK inhibitor-defactinib to construct a niche to inhibit hypertrophy and vascularization of BMSCs-engineered cartilage, finally preventing phenotype lose. For this purpose, we will first prepare and characterize a stable defactinib-loaded nanofibrous scaffold that has controlled release of drug via electrospinning. Then the anti-hypertrophy and anti-vascularization capability of the scaffold will be investigated.At last，we will discuss the molecular mechanism how the drug-loaded scaffold functions in hypertrophy and vascularization of BMSCs-engineered cartilage under subcutaneous condition. This study is expected to provide a novel theoretical basis and construction strategy for cartilage tissue engineering.