伴大段骨缺损的复杂性骨折是骨科顽症之一，随着组织工程技术的日新月异，可降解高分子材料在修复骨缺损中已取得较好疗效。但高度仿生性、完全骨整合能力及在体降解等问题困扰当前骨生物材料的发展。本课题组最近研制出一种基于柠檬酸的新型可降解高分子材料，首次将天然骨中5%柠檬酯成分纳入材料设计，且能复合65%羟基磷灰石，最大程度模拟天然骨的构成。我们预实验发现：该材料模量和强度可与人体皮质骨相媲美且降解可调，植入兔体内6周后不产生慢性炎症反应，具有很强的骨诱导和骨整合能力；且能显著提高成骨分化早期碱性磷酸酶（ALP）和Osterix mRNA表达水平，并极大促进骨髓基质细胞(BMSCs)成骨分化过程中钙结节形成。本项目拟使用该材料联合BMSCs细胞移植，在大动物（山羊）水平，进一步研究其修复大段骨缺损的近期和远期疗效及其作用机制，并在体外探讨柠檬酸促进成骨分化的分子机制。为该材料今后进入临床提供实验依据.

Complicated fractures combined with large bone defects have always been one of the most challengeable diseases in orthopedics. However, with the increasingly development of tissue engineering technology, biodegradable polymer materials have achieved good effects in the treatment of these diseases, highly biomimetic, complete osseointegration, and side-effect-free biodegradation in vivo are the main problem faced with present biomaterials. Recently, we developed a biodegradable, mechanically strong, citrate-based polymer blend/HA (CBPBHA) composite with a compressive strength of 116.23 ± 5.37 MPa similar to that of human cortical bone without altering their osteoinductivity and osteoconductivity. In our preliminary experiment, the composites perform well integrated with the host bone with almost no fibrous tissue encapsulation after 6 weeks of implantation into the lateral femoral condyles of rabbit knees. What's more, we also found the composites can greatly up-regulate the expression of ALP and Osterix mRNA, which are the key factors in osteogenesis, during the osteogenic differentiation of C2C12. Besides, what makes we more interesting is that, the citric acid can obviously enhance the bone mineralization in the osteogenic differentiation of bone marrow stromal cells. The discovery of CBPBHA composites bridges the gap in previous bone biomaterial designs in that the role of citrate molecules was inadvertently overlooked. The CBPBHA composites represent a new generation of bone biomaterials which offers new opportunities to tackle the challenges in bone tissue engineering and in the treatment of orthopedics persistent diseases. In this research, we intend to further study the short and long-term effects of CBPBHA scaffolds combined with bone marrow stromal cells transplantation in the management of goats' large bone defects, and to further explore the mechanism of its bone mineralization enhancement.