Biomedical Engineering Reference
In-Depth Information
9.5
Surface Biology of Specific Cell-Scaffold Interactions
The facts describing the surface chemistry of an active and an inactive scaffold pro-
vide a fuller picture of what the active scaffold looks like and how it interacts with
the contractile cells. The interaction leads to blocking of a central function of these
cells and amounts, therefore, to a profound change in cell phenotype.
Strikingly, maximum blocking of contraction and highest quality of regeneration
coincided with a single scaffold with narrowly defined structure, DRT. A very large
number of other collagen-based scaffolds, closely related in structure to DRT but
not identical to it, did not show either contraction-inhibiting activity or regenerative
activity. The facts confirm the presence of a surface with high degree of specific-
ity for cell-matrix interactions. Critical structural properties characterize DRT as
a unique scaffold that applies an effective contraction blockade while inducing re-
generation of high quality both in skin wounds and peripheral nerve wounds. These
features are the pore size, which controls cell entry into the scaffold and provides
specific surface for cell attachment; the half-life, which provides a time window
during which cells and scaffold can make contact; the ligand density which enables
the adhesive interaction between cell-binding integrins and scaffold surface that
affects so profoundly the assembled morphology and contractile function of these
cells. There are echoes here of heterogeneous catalysis of chemical reactions, where
chemical reactants diffuse to the catalytic surface and adsorb on it, forming rapidly
reacting species that change the pathway or rate of the reaction.
Biological processes are usually studied in dilute cell culture media and catalytic
activity derives from soluble macromolecules (enzymes, cytokines) which mediate
enzyme-substrate interactions that speed biological reactions. The evidence pre-
sented in this chapter shows that the substance which modifies the phenotype of
contractile cells is an insoluble surface. These considerations introduce the concept
of surface biology, a biology that derives its functions from specific interactions of
cells with an insoluble solid surface (Fig.
9.7
).
Fig. 9.7
Quantitative analysis of ligands of α1β1 and α2β1 integrins in three collagen scaffolds
used in peripheral nerve regeneration. The three scaffolds were crosslinked at different levels and
exhibited sharp differences in regenerative activity. Scaffold A, uncrosslinked baseline control; D,
crosslinked lightly, active; E, crosslinked heavily, inactive. Concentration of ligands on the col-
lagen surface for α1β1 and α2β1 integrins is shown on the vertical axis (Tzeranis 2013)
