Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Hohe Strasse 6, 01069 Dresden, Germany.
Biomaterials. 2011 Oct;32(30):7444-53. doi: 10.1016/j.biomaterials.2011.06.031. Epub 2011 Jul 23.
Collagen-based biomaterials are currently used as cell culture scaffolds in tissue engineering approaches. These materials are being developed with increased functional complexity, such as the incorporation of glycosaminoglycans. Our study shows the impact of heparin intercalation at specific binding sites in telopeptide-free collagen fibrils in terms of their structure, mechanics, and cell response. We demonstrate that heparin binds specifically and in a competitive manner along the tropocollagen helix at places that are occupied in vivo by telopeptides in fibrillar collagen type I. On the basis of this finding, we elucidate the reason for the in vivo dogma that heparin does not intercalate in fibrillar collagens. We further reveal the direct relationship among structure, mechanics, and function in terms of the effect of incorporation of intercalated heparin on the fibrillar structure, fibrillar bending modulus and flexural rigidity and the dynamic response of adherent cells to collagen scaffolds. This tight relationship is considered particularly important when designing xenogeneic scaffolds based on natural collagen type I to trigger cell proliferation and differentiation.
基于胶原蛋白的生物材料目前被用作组织工程方法中的细胞培养支架。这些材料的功能复杂性不断提高，例如加入糖胺聚糖。我们的研究表明，在无末端肽的胶原蛋白原纤维中，肝素在特定结合部位的插入对其结构、力学和细胞反应有影响。我们证明肝素在原胶原螺旋上以特定的、竞争的方式结合，这些部位在纤维状 I 型胶原蛋白中被末端肽占据。基于这一发现，我们阐明了肝素不在纤维状胶原蛋白中插入的体内教条的原因。我们进一步揭示了结构、力学和功能之间的直接关系，即插入的肝素对纤维状结构、纤维弯曲模量和挠曲刚度以及粘附细胞对胶原蛋白支架的动态反应的影响。当设计基于天然 I 型胶原蛋白的异种支架以触发细胞增殖和分化时，这种紧密的关系被认为尤为重要。
