Department of Materials, Imperial College London, London, United Kingdom.
Tissue Eng Part A. 2011 Nov;17(21-22):2713-22. doi: 10.1089/ten.TEA.2011.0059. Epub 2011 Aug 29.
The development of bone replacement materials is an important healthcare objective due to the drawbacks of treating defects with bone autografts. In this work we propose a bone tissue engineering approach in which arginine-glycine-aspartic acid (RGD)-modified alginate hydrogels are crosslinked with bioactive strontium and zinc ions as well as calcium. Strontium was chosen for its ability to stimulate bone formation, and zinc is essential for alkaline phosphatase (ALP) activity. Calcium and strontium gels had similar stiffnesses but different stabilities over time. Strontium gels made with alginate with a high percentage of guluronic acid residues (high G) were slow to degrade, whereas those made with alginate rich in mannuronic acid (high M) degraded more quickly, and supported proliferation of Saos-2 osteoblast-like cells. After an initial burst, strontium release from alginate gels was steady and sustained, and the magnitude of release from high M gels was biologically relevant. Saos-2 cultured within alginate gels upregulated the osteoblast phenotypic marker genes RUNX2, collagen I (COL1A1) and bone sialoprotein (BSP), and ALP protein activity was highest in alginate gels cast with strontium ions. This strategy has the potential to be combined with other alginate-based systems for bone tissue engineering, or adapted to other tissue engineering applications.
由于骨移植治疗缺陷存在的缺点，开发骨替代材料是一个重要的医疗保健目标。在这项工作中，我们提出了一种骨组织工程方法，其中精氨酸-甘氨酸-天冬氨酸（RGD）修饰的藻酸盐水凝胶与生物活性锶和锌离子以及钙交联。选择锶是因为它具有刺激骨形成的能力，而锌对于碱性磷酸酶（ALP）活性是必需的。钙和锶凝胶的硬度相似，但随时间的推移稳定性不同。用高比例古洛糖醛酸残基（高 G）的藻酸盐制成的锶凝胶降解缓慢，而用富含甘露糖醛酸（高 M）的藻酸盐制成的凝胶降解更快，并支持 Saos-2 成骨样细胞的增殖。在初始爆发后，藻酸盐凝胶中锶的释放稳定且持续，并且从高 M 凝胶中的释放量具有生物学相关性。在藻酸盐凝胶中培养的 Saos-2 上调了成骨细胞表型标记基因 RUNX2、胶原蛋白 I（COL1A1）和骨涎蛋白（BSP），并且在锶离子铸造的藻酸盐凝胶中 ALP 蛋白活性最高。该策略有可能与其他基于藻酸盐的骨组织工程系统结合，或适应其他组织工程应用。
