Surface Chemistry of Nanoscale Mineralized Collagen Regulates Periodontal Ligament Stem Cell Fate
Surface Chemistry of Nanoscale Mineralized Collagen Regulates Periodontal Ligament Stem Cell Fate
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DOI：
10.1021/acsami.6b04951
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发表时间：
2016-06-29
影响因子：
9.5
通讯作者：
Zhou, Yan-Heng
中科院分区：
文献类型：
--
作者：
Fu, Yu;Liu, Shuai;Zhou, Yan-Heng
干细胞与其细胞外微环境之间的相互作用对于再生医学中基于干细胞的治疗至关重要。矿化胶原是骨细胞外基质的主要成分，但矿化胶原的界面性质对后续细胞行为的影响尚不清楚。这项研究考察了纳米级矿化胶原的表面化学对人牙周膜干细胞(HPDLSC)命运决定的作用。通过仿生自下而上的方法制备的纤维内矿化胶原(IMC)呈现出骨状的层次结构，纳米羟基磷灰石(HAS)周期性地嵌入纤维中。IMC的红外光谱显示存在磷酸盐、碳酸盐、酰胺I和II带，红外图谱显示IMC中矿化的空间分布均匀且较高。然而，在纤维外矿化胶原(EMC)中，磷酸基团的分布与酰胺I基团的分布有很大的不同，在EMC中，花状HA簇随机沉积在纤维表面。此外，大量的纤维外纤维掩盖了C=-O拉伸和N-H面内弯曲，导致酰胺I和II带大幅减少。细胞实验表明，种植在IMC上的hPDLSCs呈高度分枝的成骨细胞样多边形，伪足延长，应力纤维形成粗大；而种植在EMC上的细胞呈纺锤形，分支点较少，肌动蛋白原纤维较薄。此外，EMC的生物相容性远低于IMC。有趣的是，即使在没有成骨诱导的情况下，主要成骨分化基因的mRNA水平在培养期间在IMC中也是高表达的。这些数据表明，具有与天然矿化胶原相似的纳米形貌和表面化学的IMC可以引导hPDLSCs向成骨细胞分化，为骨组织再生提供了一种有前景的支架。
The interplay between stem cells and their extracellular microenvironment is of critical importance to the stem cell-based therapeutics in regenerative medicine. Mineralized collagen is the main component of bone extracellular matrix, but the effect of interfacial properties of mineralized collagen on subsequent cellular behaviors is unclear. This study examined the role of surface chemistry of nanoscale mineralized collagen on human periodontal ligament stem cell (hPDLSC) fate decisions. The intrafibrillarly mineralized collagen (IMC), fabricated by a biomimetic bottom-up approach, showed a bonelike hierarchy with nanohydroxyapatites (HAs) periodically embedded within fibrils. The infrared spectrum of the IMC showed the presence of phosphate, carbonate, amide I and II bands; and infrared mapping displayed uniform and higher spatial distribution of mineralization in the IMC. However, the distribution of the phosphate group differed far from that of the amide I group in the extrafibrillarly mineralized collagen (EMC), in which flowerlike HA clusters randomly depositing around the surface of the fibrils. Moreover, a large quantity of extrafibrillar HAs covered up the C=-O stretch and N-H in-plane bend, resulting in substantial reduction of amide I and II bands. Cell experiments demonstrated that the hPDLSCs seeded on the IMC exhibited a highly branched, osteoblast-like polygonal shape with extended pseudopodia and thick stress fiber formation; while cells on the EMC displayed a spindle shape with less branch points and thin actin fibril formation. Furthermore, the biocompatibility of EMC was much lower than that of IMC. Interestingly, even without osteogenic induction, mRNA levels of major osteogenic differentiation genes were highly expressed in the IMC during cultivation time. These data suggest that the IMC with a similar nanotopography and surface chemistry to natural mineralized collagen directs hPDLSCs toward osteoblast differentiation, providing a promising scaffold in bone tissue regeneration.