Department of Biomedical Engineering, Washington University in St. Louis, USA.
Department of Biomedical Engineering, Washington University in St. Louis, USA; Department of Orthopedic Surgery, Atrium Health Musculoskeletal Institute, USA.
Biomaterials. 2020 Aug;250:120057. doi: 10.1016/j.biomaterials.2020.120057. Epub 2020 Apr 22.
Cells of the nucleus pulposus have been observed to undergo a shift from their notochordal-like juvenile phenotype to a more fibroblast-like state with age and maturation. It has been demonstrated that culture of degenerative adult human nucleus pulposus cells upon soft (<1 kPa) full length laminin-containing hydrogel substrates promotes increased levels of a panel of markers associated with the juvenile nucleus pulposus cell phenotype. In the current work, we observed an ability to use soft polymeric substrates functionalized with short laminin-mimetic peptide sequences to recapitulate the behaviors elicited by soft, full-length laminin containing materials. Furthermore, our work suggests an ability to mimic features of soft systems through control of peptide density upon stiffer substrates. Specifically, results suggest that stiffer polymer-peptide hydrogel substrates can be used to promote the expression of a more juvenile-like phenotype for cells of the nucleus pulposus by reducing adhesive ligand presentation. Here we show how polymer stiffness combined with adhesive ligand presentation can be controlled to be supportive of nucleus pulposus cell phenotype and biosynthesis.
随着年龄的增长和成熟，椎间盘细胞已被观察到从类脊索的幼年表型向更成纤维细胞样状态转变。已经证明，在软（<1kPa）全长层粘连蛋白含量的水凝胶基质上培养退行性成人椎间盘细胞，可促进与幼年椎间盘细胞表型相关的一系列标志物水平的增加。在目前的工作中，我们观察到使用短层粘连蛋白模拟肽序列功能化的软聚合物基底来重现由软全长层粘连蛋白组成的材料引起的行为的能力。此外，我们的工作表明，通过在更硬的基底上控制肽密度，可以模拟软系统的特征。具体而言，结果表明，通过减少粘附配体的呈现，更硬的聚合物-肽水凝胶基底可用于促进椎间盘细胞表达更类似幼年的表型。在这里，我们展示了如何控制聚合物的硬度与粘附配体的呈现，以支持椎间盘细胞的表型和生物合成。
