Effects of the Fiber and Tube Size
The protein adsorption on the reinforced scaffolds should be influenced by the size of the incorporated fibers and tubes as well. It has been proved that the amount of the adsorbed proteins on nanofibers, including total serum protein, fibronectin and vitronectin is much larger than that on microfibers because of the high surface area to volume ratio . In addition to the protein amount, the conformation of the adsorbed proteins is also affected by fiber diameter. Vertegel et al.  found that the structure and enzymatic activity of the adsorbed lysozyme was strongly influenced by the size of silica nanoparticles. Particularly, greater loss of a helicity and thus greater loss of enzyme activity were observed for the lysozyme adsorbed onto larger nanoparticles. This might be attributed to the divergent curvature for nanoparticles with different diameter. It has been proved that the protein-material interaction depends on the curvature of the material surface . Specifically, a small globular protein, namely albumin, demonstrated a native-like conformation on surfaces with high curvature yet became denatured upon binding to surfaces with low curvature; on the other hand, a rod-like shape protein, namely fibrinogen, was denatured on nanospheres with higher curvature (Fig. 5.5) .
Fig. 5.5 Schematic demonstrating control of protein conformation and orientation by surface curvature. Global albumin took native conformation on surfaces with lower curvature yet became denatured on surfaces with larger curvature. In contrast, rod-like fibrogen took native conformation on surfaces with larger curvature yet became denatured on surfaces with lower curvature 
Similarly, nanofibers of different diameter are different in surface curvature. More complex surface curvatures are encountered by nanotubes. In addition to the divergent curvature caused by diameters, their inner surface and outer surface may have totally divergent curvature even for the same tubes. Therefore, it is reasonably claimed that the incorporated fibers and tubes in the fiber/tube reinforced scaffolds should regulate the protein adsorption via their fiber or tube size. Li et al.  employed CNT compacts to study the protein adsorption in 10% fetal bovine serum and found that CNT could adsorb more proteins including bone-inducing proteins. Enhanced protein adsorption was also observed by other groups . The suggested mechanism is that the dimensionality of CNT is comparable with that of natural ECM proteins in addition to the increased specific area [36, 37]. Despite the increased protein amount, the conformational changes in both secondary and tertiary structures of the adsorbed proteins might be rendered on carbon nanotubes surface [38, 39], which may be advantageous or disadvantageous to cell responses. To more clearly uncover the controlling mechanism for protein adsorption by nanotube size, Shen et al.  investigated the interaction between human serum albumin and carbon nanotubes by using dynamics simulations. They found that the interaction between albumin and carbon nanotubes becomes strengthened with the increase of tube diameter. Furthermore, the atoms near the tube wall rearrange to fit the curving surfaces of carbon nanotubes; thereby, the final conformation and orientation of albumin are altered on the tubes and exhibit curvature-dependence (Fig. 5.6) . There is an interesting observation about the effect of fiber diameter
Fig. 5.6 The final conformations (left) of the adsorbed human serum albumin on carbon nanotubes of different diameters and the corresponding residues (right), including basic residues (blue), acidic residues (red), non-polar residues (gray) and polar residues (green) 
Fig. 5.7 Schematic of the protein adsorption mechanism 
on protein adsorption. It is found that the protein amount adsorbed on random nanofibrous scaffolds increased with the decrease of fiber diameter , whereas on homogenously aligned nanofibrous scaffolds, similar protein amount was observed regardless of the fiber diameter . This suggests that protein adsorption is regulated by fiber alignment as well.