Swartzlander Mark D, Barnes Christopher A, Blakney Anna K, Kaar Joel L, Kyriakides Themis R, Bryant Stephanie J
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA; Biofrontiers Institute, University of Colorado, Boulder, CO 80309, USA.
Institute of Biochemistry, ETH Zürich, Switzerland.
Biomaterials. 2015 Feb;41:26-36. doi: 10.1016/j.biomaterials.2014.11.026. Epub 2014 Dec 2.
Poly(ethylene glycol) (PEG) hydrogels with their highly tunable properties are promising implantable materials, but as with all non-biological materials, they elicit a foreign body response (FBR). Recent studies, however, have shown that incorporating the oligopeptide RGD into PEG hydrogels reduces the FBR. To better understand the mechanisms involved and the role of RGD in mediating the FBR, PEG, PEG-RGD and PEG-RDG hydrogels were investigated. After a 28-day subcutaneous implantation in mice, a thinner and less dense fibrous capsule formed around PEG-RGD hydrogels, while PEG and PEG-RDG hydrogels exhibited stronger, but similar FBRs. Protein adsorption to the hydrogels, which is considered the first step in the FBR, was also characterized. In vitro experiments confirmed that serum proteins adsorbed to PEG-based hydrogels and were necessary to promote macrophage adhesion to PEG and PEG-RDG, but not PEG-RGD hydrogels. Proteins adsorbed to the hydrogels in vivo were identified using liquid chromatography-tandem mass spectrometry. The majority (245) of the total proteins (≥300) that were identified was present on all hydrogels with many proteins being associated with wounding and acute inflammation. These findings suggest that the FBR to PEG hydrogels may be mediated by the presence of inflammatory-related proteins adsorbed to the surface, but that macrophages appear to sense the underlying chemistry, which for RGD improves the FBR.
聚乙二醇（PEG）水凝胶具有高度可调节的特性，是很有前景的可植入材料，但与所有非生物材料一样，它们会引发异物反应（FBR）。然而，最近的研究表明，将寡肽RGD掺入PEG水凝胶中可降低FBR。为了更好地理解其中涉及的机制以及RGD在介导FBR中的作用，对PEG、PEG-RGD和PEG-RDG水凝胶进行了研究。在小鼠皮下植入28天后，PEG-RGD水凝胶周围形成的纤维囊更薄且密度更低，而PEG和PEG-RDG水凝胶表现出更强但相似的FBR。还对水凝胶上的蛋白质吸附进行了表征，这被认为是FBR的第一步。体外实验证实，血清蛋白吸附到基于PEG的水凝胶上，并且是促进巨噬细胞粘附到PEG和PEG-RDG（而非PEG-RGD水凝胶）所必需的。使用液相色谱-串联质谱法鉴定了体内吸附到水凝胶上的蛋白质。在所有水凝胶上均鉴定出了大多数（245种）总蛋白质（≥300种），其中许多蛋白质与伤口愈合和急性炎症相关。这些发现表明，对PEG水凝胶的FBR可能由吸附在表面的炎症相关蛋白质介导，但巨噬细胞似乎能感知潜在的化学性质，对于RGD而言，这改善了FBR。
