Nb2C MXene/BG复合支架负载hBMSCs来源的肥大软骨细胞修复巨大骨缺损的实验研究

巨大骨缺损是临床医师面临的重要挑战。经典的组织工程技术给骨缺损治疗带来了曙光，但仍然存在治疗效率不高、血管形成和骨再生失衡等难题。我们前期研究证实，通过构建经Nb2C MXene二维材料处理的三维BG复合支架，可诱导血管再生和骨形成偶联，促进骨缺损修复。基于发育工程学理念，本研究进一步提出假说：负载肥大软骨细胞的Nb2C MXene/BG复合支架可加速骨-血管生成偶联过程，并高效修复巨大骨缺损。为验证该假说，我们通过体外共培养模型，验证Nb2C MXene/BG对肥大软骨细胞转分化、骨形成和模拟血管生成的影响；Sox9的可调控性表达在材料诱导骨再生过程中可能发挥了重要作用，并与促血管生成因子的表达密切相关。我们进一步构建模型动物的异位成骨模型及多种巨大骨缺损动物模型，采用免疫学、组织学、影像学、生物力学及功能学等方法，评价Nb2C MXene/BG负载肥大软骨细胞在骨缺损修复中的价值。

Massive bone defect is one of greatest challenges in clinical practice. Although conventional tissue engineering has shed light on the reconstruction of bone defects, both unsatisfactory therapeutic efficiency and uncoupled vascular regeneration and bone formation are critical obstacles in the translational investigations. In our privious studies, we constructed two-dimensional (2D) Nb2C MXene-integrated 3D-printing bioglass (BG) scaffold (Nb2C MXene/BG), which demonstrated a high promotion of coupled vascularization and bone formation, thus to efficiently repair the bone defects. With a further combination with the concept of developmental engineering, we hypothesized that the Nb2C MXene/BG composite scaffold-loading hypertrophic chondrocytes could achieve a synchronized regeneration of osseous and vascular structure, to promisingly restore the massive bone defects. To test our scientific hypothesis, we will employ several coculture models in vitro to reveal the effect of Nb2C MXene/BG in the transdifferentiation of hypertrophic chondrocytes, bone formation and angiogenesis. In the process of material-induced osseous regeneration, the tunable expression of Sox9 might play a critical role and intimately communicate with angiogenic factors. Furthermore, we will establish the model of ectopic bone formation within transgenic animals as well as multiple rat models with massive bone defects, using a cascade of immunological, histopathological, radiographical, biomechanical and functional methods, to evaluate the significance of Nb2C MXene/BG and hypertrophic chondrocytes complex in the repair of bone defects.