Abstract
To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations.
Highlights
The key features of biomaterials scaffolds which are attractive for tissue regenerations are unclear numerous researchers have been investigating the biological reactions to various materials in vitro and in vivo
In poly(MPC-co-n-butyl methacrylate (BMA)) (PMB)-coated film, unique absorption peaks at 1240, 1080, and 970 cm21 were observed. These peaks corresponded to the phosphate group (P-O) in the MPC unit in PMB [33]
It is confirmed that PE scaffold surface can be coated with collagen and PMB successfully
Summary
The key features of biomaterials scaffolds which are attractive for tissue regenerations are unclear numerous researchers have been investigating the biological reactions to various materials in vitro and in vivo. Cell responses are affected by structure, physical properties, and the chemical properties of the scaffold [1,2]. The size and shape of nano and microparticles modulate phagocytosis of macrophages, and mechanical strain as a physical property affects macrophage hydrolytic activation [3,4]. It is known that not all chemically biocompatible materials are adequate for tissue regeneration. Hyaluronan is sometimes clinically used as post-operative tissue adhesion prevention matrices due to noncytotoxic and biodegradable [5,6]. Its hydrophilic surface property may disturb the cell adhesion and tissue regeneration when used as a scaffold
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