Regulation of Cell/Tissue Responses by Biochemical Cues of Scaffolds

Since the reinforcing nanofibers or nanotubes are different with the bulk scaffolds in chemical compositions, incorporation of nanofibers or nanotubes into the scaffolds may change the chemical cues provided to cells on scaffolds. As described in Sect. 5.3, the chemical composition of a material will affect the type, quantity and activity of the adsorbed proteins, which may subsequently regulate the cell-material interactions. For instance, Allen et al. showed differential gene expression for several cell types on various chemistries [126]. Our previous studies indicated that material chemistry regulates the sensitivity of osteoblasts to various magnitudes of fluid shear stress and the potential mechanism was that the surface chemistry influences the cell adhesion and morphology which further regulate the perceiving and responding of osteoblasts to the fluid shear stress [68, 70]. For 3D scaffolds such as poly(lactic acid) (PLA), its strong hydrophobicity due to the existence of CH3 side chains and ester backbone may inhibit cell adhesion and proliferation. Incorporation of hydrophilic cellulose nanofibers into PLA scaffolds was found to facilitate proteins adsorption in an appropriate geometrical orientation and thus promote cell adhesion [78, 127]. Similarly, incorporation of collagen-derived biopolymer gelatin (Gt) into PCL scaffolds can also increase the hydrophilicity of PCL scaffolds and further promote cell proliferation and infiltration into the scaffolds [128]. For nanofibers lacking in hydrophilic chemistries, surface modification could be used to optimize the nanofibers [129]. For example, Chuan et al. found that surface-aminated electrospun polyethersulfone nanofibers could enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells [130]. In addition to the modulation of surface hydrophilicity, incorporation of biocompatible nanofibers into scaffolds can also provide recognition sites for cells and thus enhance biological affinity of the resulting composite scaffolds. For instance, it has been reported that chitosan can promote adhesion and functional expression of osteoblasts because of its similarity to glycosaminoglycan in structure [107, 131]. Besides, Grafahrend et al. [132] designed a type of functionalized PLGA nanofibers with both GRGDS adhesive peptide and star-shaped poly(ethylene oxide), the latter of which is a polymer capable of suppress non-specific protein adsorption. The resulting nanofibers promoted specific bioactivation and enabled adhesion of cells through exclusive recognition of the immobilized binding motifs. Similarly, potential cytotoxic effects associated with nanofibers such as carbon nanotube may be mitigated by chemically functionalizing the surface [133]. Meanwhile, the functionalized carbon nanotubes generally demonstrate better dispersibility in water compared to their intact ones, which further extends the potential of nanotubes for biomedical applications [94].

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