Scaffold Design for Bone Tissue Engineering: From Micrometric to Nanometric Level - Biologically Responsive Biomaterials for Tissue Engineering - page 6

Through the time-controlled resizing of pores which occurs during degradation,
materials with a predictable degradation rate may guarantee greater penetration of
extracellular substance, improve the nutrient/metabolites exchange, and offer a
better connection between neighboring cells, encouraging and promoting the
growth of new tissue. The influence of several factors on degradation kinetics may
be considered, including molecular factors (e.g., chain orientation, molecular
weight, and polydispersity), supramolecular factors (crystallinity, spatial distribu-
tion of chemically reactive filler), and environmental factors (e.g., mechanical
stimuli), to potentially generate a wide range of resorbable properties for custom-
made systems. Despite its relevance on affecting specific biological mechanisms at
different time scale, the evolution of structural properties in connection with the
selective degradation of specific components of the scaffold matrix has not been
adequately explored.
The integration of highly degradable materials, obtained by chemical modification
of purified hyaluronan (HA), namely, HYAFF11 ® , formed by the partial or total
esterification of the carboxyl groups of glucuronic acid with different types of alco-
hols gives the opportunity of directly affecting the cell activities, either favoring or,
conversely, inhibiting the adhesion of certain cell types [ 32 ] . In particular, partially
esteri fi ed HYAFF11 ® with reduced hydrophilic, negatively charged, carboxyl groups
along the polymer backbone—esterification degree equal to 75 %—shows a pecu-
liar hydrophilic/hydrophobic character which confers an adequate biological recog-
nition, without drastically penalizing the structural integrity of the composite
scaffold at the preliminary stage of the culture [ 21 ] .
In this case, the scaffold functionality is efficiently reached through the right
balance between porosity requirements, reinforcement systems, and degradation
properties. In particular, the accurate modulation of porosity features and degrada-
tion properties on different dimensional scales allows reaching tailored systems
able to regulate specific cell mechanisms and to guide the ultimate tissue forma-
tion. Also in this case, PLA fibers or bioactive ceramic particles, in turn, further
improve the mechanical response of the scaffolds partially limited by the high pore
volume fraction, needful for the accommodation of bone cells and their mainte-
nance, matching the mechanical behavior of trabecular bone. Finally, the presence
of highly hydrophilic Hyaff11 ® positively contributes to growth factor entrapment/
release as well as to cell recognition, as confirmed by preliminary evaluation of the
attachment and MSC cell proliferation, adumbrating the potential in vivo success
of tubular scaffolds.

1.4 Surface and Bulk Bioactivation

Novel strategies for regenerating diseased or damaged bone tissue are necessary
because of the limitations of established therapies for the treatment of congenital
defects and other bone trauma. The development of new materials able to structur-
ally, mechanically, and bio-functionally interface with natural tissues is relevant to