Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 20742, USA.
J Biomed Mater Res A. 2010 Aug;94(2):408-18. doi: 10.1002/jbm.a.32683.
Cyclic acetal hydrogels are a novel group of biomaterials which may facilitate osteogenic differentiation of encapsulated bone marrow stromal cells (BMSCs) because of their neutral degradation products. Here, we have incorporated hydroxyapatite nanoparticles within cyclic acetal hydrogels to create cyclic acetal nanocomposites for craniofacial tissue engineering applications. We hypothesized that inclusion of nanosized hydroxyapatite particles within cyclic acetal hydrogels would upregulate osteogenic signal expression of encapsulated BMSCs, due to enhanced cell adhesion, and therefore promote osteodifferentiation. Experimental nanocomposite groups consisted of lower (5 ng/mL) and higher (50 ng/mL) concentrations of nanoparticles. The nanocomposites were characterized by scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. Swelling parameters of hydrogels in the presence of nanoparticles was studied. Osteoblastic differentiation was characterized by alkaline phosphatase (ALP) and osteocalcin (OC) expression, whereas endogenous osteogenic signal expression was characterized by morphogenetic protein-2 (BMP-2) expression. Finally, immunohistochemistry was performed to detect the presence of OC at the protein level. Results indicated that hydroxyapatite nanoparticles were uniformly distributed throughout the hydrogels and did not affect material properties of the gels. Viability of cells was not affected by nanoparticle concentration, and BMP-2 and OC mRNA expression was enhanced in the presence of nanoparticles. However, a difference in BMP-2, ALP, and OC mRNA expression was not noted between the lower and higher concentrations of nanoparticles. This work demonstrates that inclusion of hydroxyapatite nanoparticles within a cyclic acetal nanocomposite hydrogel may enhance BMSC differentiation by promoting endogenous osteogenic signal expression.
环状缩醛水凝胶是一类新型的生物材料，由于其中性降解产物，可能有助于包封的骨髓基质细胞（BMSCs）的成骨分化。在这里，我们将纳米羟基磷灰石颗粒掺入环状缩醛水凝胶中，以创建用于颅面组织工程应用的环状缩醛纳米复合材料。我们假设，由于增强了细胞黏附作用，将纳米级羟基磷灰石颗粒掺入环状缩醛水凝胶中会上调包封的 BMSCs 的成骨信号表达，从而促进成骨分化。实验性纳米复合材料组由较低（5ng/mL）和较高（50ng/mL）浓度的纳米颗粒组成。通过扫描电子显微镜、透射电子显微镜和能量色散光谱对纳米复合材料进行了表征。研究了纳米颗粒存在下水凝胶的溶胀参数。通过碱性磷酸酶（ALP）和骨钙素（OC）的表达来表征成骨细胞分化，而内源性成骨信号的表达则通过形态发生蛋白-2（BMP-2）的表达来表征。最后，进行了免疫组织化学检测以检测 OC 在蛋白质水平上的存在。结果表明，纳米羟基磷灰石均匀分布在水凝胶中，且不影响凝胶的材料性能。纳米颗粒浓度对细胞活力没有影响，并且在存在纳米颗粒的情况下，BMP-2 和 OC mRNA 的表达增强。然而，在较低和较高浓度的纳米颗粒之间，BMP-2、ALP 和 OC mRNA 的表达没有差异。这项工作表明，在环状缩醛纳米复合水凝胶中加入纳米羟基磷灰石颗粒可以通过促进内源性成骨信号表达来增强 BMSC 的分化。
