Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, USA.
J Biomed Mater Res A. 2010 Jul;94(1):112-21. doi: 10.1002/jbm.a.32695.
Ligament graft failure frequently results from poor integration of the replacement tissue with associated bone. Thus, the ability to regenerate the bone-ligament osteochondral interface would be advantageous in ligament reconstruction. At the osteochondral interface, the tissue transitions from a bone-like matrix to fibrocartilage. Therefore, a scaffold which promotes a spatially regulated transition in cell behavior from osteoblast-like to chondrocyte-like would be desirable. Previous research indicates that addition of inorganic components to organic scaffolds can enhance the deposition of bone-like matrix by associated osteoblasts. We therefore reasoned that a gradient in the inorganic content of a hybrid inorganic-organic scaffold may induce an osteochondral-like transition in cell phenotype and matrix production. To test this hypothesis, hydrogels were prepared from poly(ethylene glycol) (PEG) and star poly(dimethylsiloxane) (PDMS(star)). As anticipated, both the matrix deposition and phenotype of encapsulated osteoblasts varied with scaffold inorganic content, although the directionality of this modulation was contrary to expectation. Specifically, osteoblasts appeared to transdifferentiate into chondrocyte-like cells with increasing scaffold inorganic content, as indicated by increased chondroitin sulfate and collagen type II production and by upregulation of sox9, a transcription factor associated with chondrocytic differentiation. Furthermore, the deposition of bone-like matrix (collagen type I, calcium phosphate, and osteocalcin) decreased with increasing PDMS(star) content. The resistance of the PDMS(star)-PEG scaffolds to protein adsorption and/or the changes in gel modulus/mesh structure accompanying PDMS(star) incorporation may underlie the unexpected increase in chondrocytic phenotype with increasing inorganic content. Combined, the present results indicate that PDMS(star)-PEG hybrid gels may prove promising for osteochondral regeneration. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
韧带移植物的失效通常是由于替代组织与相关骨的整合不良所致。因此，能够再生骨-韧带-软骨界面将有利于韧带重建。在骨-软骨界面，组织从骨样基质转变为纤维软骨。因此，需要一种支架来促进细胞行为从成骨样向软骨样的空间调节转变。先前的研究表明，向有机支架中添加无机成分可以增强相关成骨细胞对骨样基质的沉积。因此，我们推断混合无机-有机支架中无机成分的梯度可能会诱导细胞表型和基质产生的类软骨-骨转变。为了验证这一假设，我们用聚乙二醇（PEG）和星形聚二甲基硅氧烷（PDMS(star)）制备了水凝胶。正如预期的那样，封装的成骨细胞的基质沉积和表型都随支架无机含量的变化而变化，尽管这种调节的方向性与预期相反。具体而言，随着支架无机含量的增加，成骨细胞似乎向软骨样细胞发生转分化，这表现在硫酸软骨素和 II 型胶原的产生增加，以及与软骨细胞分化相关的转录因子 sox9 的上调。此外，随着 PDMS(star)含量的增加，骨样基质（I 型胶原、磷酸钙和骨钙素）的沉积减少。PDMS(star)掺入引起的 PDMS(star)-PEG 支架对蛋白质吸附的抵抗力和/或凝胶模量/网格结构的变化可能是无机含量增加导致软骨样表型增加的原因。综上所述，本研究结果表明，PDMS(star)-PEG 杂化凝胶可能在骨软骨再生方面具有广阔的应用前景。（c）2010 Wiley 期刊，Inc. J Biomed Mater Res，2010.
