Allison D D, Braun K R, Wight T N, Grande-Allen K J
Rice University, Department of Bioengineering, 6100 Main St., MS 142, Houston, TX 77005, USA.
Acta Biomater. 2009 May;5(4):1019-26. doi: 10.1016/j.actbio.2008.11.013. Epub 2008 Dec 6.
The addition of exogenous hyaluronan to biomaterial scaffolds has been an important area of investigation for many decades. The ability to manipulate endogenous production of hyaluronan via the hyaluronan syntheses has offered another mechanism to study the effect of hyaluronan. While the literature suggests that exogenously added hyaluronan and endogenously produced hyaluronan will have varying impacts on extracellular matrix organization and function, no studies have directly shown this phenomenon. In this investigation, we demonstrate that the addition of exogenous high molecular weight (approximately 1 MDa) hyaluronan and hyaluronan oligosaccharides have a distinct impact on both contraction and strength of smooth muscle cell-seeded collagen gels when compared to the effects of hyaluronan that is endogenously produced by the hyaluronan synthases. More specifically, the addition of exogenous high molecular weight hyaluronan resulted in more compact collagen gels with a higher ultimate tensile strength, whereas the endogenous overproduction of hyaluronan resulted in the opposite effect. We suggest that the addition of exogenous HA to collagen gels represents a model for the therapeutic administration of HA, whereas the addition of excess HA to a tissue via the endogenous overexpression of has represents a model for the pathological accumulation of HA.
几十年来，向生物材料支架中添加外源性透明质酸一直是一个重要的研究领域。通过透明质酸合成来调控内源性透明质酸的产生，为研究透明质酸的作用提供了另一种机制。虽然文献表明，外源性添加的透明质酸和内源性产生的透明质酸对细胞外基质的组织和功能会有不同的影响，但尚无研究直接证明这一现象。在本研究中，我们证明，与透明质酸合酶内源性产生的透明质酸相比，添加外源性高分子量（约1 MDa）透明质酸和透明质酸寡糖对接种平滑肌细胞的胶原凝胶的收缩和强度有明显影响。更具体地说，添加外源性高分子量透明质酸会使胶原凝胶更致密，具有更高的极限拉伸强度，而内源性过量产生透明质酸则会产生相反的效果。我们认为，向胶原凝胶中添加外源性透明质酸代表了透明质酸治疗给药的模型，而通过内源性过表达透明质酸合酶向组织中添加过量透明质酸则代表了透明质酸病理积累的模型。
