Paderi John E, Panitch Alyssa
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA.
Biomacromolecules. 2008 Sep;9(9):2562-6. doi: 10.1021/bm8006852. Epub 2008 Aug 5.
The ubiquity of collagen in mammalian tissues, with its host of structural and chemical functions, has motivated its research in many fields, including tissue engineering. The organization of collagen is known to affect cell behavior and the resulting structural integrity of tissues or tissue engineered scaffolds. Of particular interest are proteoglycan (PG) interactions with collagen and their influence on collagen assembly. These natural molecules provide unique chemical and mechanical cues and are known to modulate collagen fibrillogenesis. Research has been limited to PGs extracted and purified from animal sources and has the drawbacks of limited design control and costly purification. Consequently, we have designed a synthetic peptidoglycan based on decorin, a collagen-binding PG. The synthetic peptidoglycan containing a collagen-binding peptide with a single dermatan sulfate side chain specifically binds to collagen, delays fibrillogenesis, and increases collagen gel stiffness as decorin does. This design can be tailored with respect to the peptide sequence and attached glycosaminoglycan chain, offering unique control with relative ease of manufacturing.
胶原蛋白在哺乳动物组织中无处不在，具有众多结构和化学功能，这激发了其在包括组织工程在内的许多领域的研究。已知胶原蛋白的组织方式会影响细胞行为以及由此产生的组织或组织工程支架的结构完整性。特别令人感兴趣的是蛋白聚糖（PG）与胶原蛋白的相互作用及其对胶原蛋白组装的影响。这些天然分子提供独特的化学和机械信号，并且已知可调节胶原蛋白的原纤维形成。此前的研究仅限于从动物来源提取和纯化的蛋白聚糖，存在设计控制有限和纯化成本高的缺点。因此，我们基于核心蛋白聚糖（一种与胶原蛋白结合的蛋白聚糖）设计了一种合成肽聚糖。这种含有带有单个硫酸皮肤素侧链的胶原蛋白结合肽的合成肽聚糖，与核心蛋白聚糖一样，能特异性结合胶原蛋白，延迟原纤维形成，并增加胶原蛋白凝胶的硬度。这种设计可以根据肽序列和连接的糖胺聚糖链进行定制，相对易于制造，且能提供独特的控制。
