Protein-based Biointerfaces to Control Stem Cell Differentiation - Biointerfaces: Where Material Meets Biology - page 11

Presenting angiogenic growth factors and signaling markers such as VEGF
can trigger the microvessel formation process. D'Andrea et al. reported the
development of a synthetic short peptide of 15 amino acids called QK pep-
tide which contained a VEGF binding domain to activate VEGF receptors in
endothelial cells. This peptide was used to induce endothelial proliferation
and VEGF signaling mechanisms on a Matrigel substrate. 61 Synthetic small
peptides have been further modified to incorporate acrylate motifs to fa-
cilitate the functionalization of VEFG-like peptides in PEG hydrogels. 72
Additionally, Chiu et al. guided endothelial cell proliferation in a micro-
fabricated chitosan-collagen hydrogel rich in Tb4, an angiogenic and cardio-
protective peptide that enhances cardiomyocyte survival. 73,74 This approach
enabled capillary-mediated anchorage and anastomosis of arteries and
veins. 73 In a recent study, Kim et al. integrated a microfluidic chip perfused
with a fibrin gel to perform a comprehensive angiogenesis study by endo-
thelial cell-mediated formation of perfusable microcapillaries. 75 Also,
microvessels generated in a microfluidic chip presented morphological and
biochemical cues replicating those in native blood vessels and capillaries
niches. 75 The combination of these technologies offers the potential to
create bone replacement scaffolds in the future in a cost-effective and re-
producible manner. Biological techniques for pre-vascularization of bone
substitutes hold a great promise for fabrication of functional large bones
in vitro. However, there are some challenges that have limited the progress of
these methods. Challenges associated with the fabrication of vascular net-
works are the inability to form three-dimensional (3D) biomimetic vascular
networks in long bones, and the corresponding slow processing time of
these networks.

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1.2 Methods of Protein Immobilization
Over the years, many functionalization strategies have been developed and
optimized in order to add new functionalities to bio-inert materials and
broaden their applicability while overcoming any important material de-
ficiency and preserving their qualities. Approaches for protein immobiliza-
tion can generally be divided in two groups: (1) surface functionalization,
when only the surface is involved in the modification process, commonly
through a post-processing step; and (2) bulk functionalization, when the
material is homogenously modified, usually before or during the processing.
Here, we will focus on these two approaches for introducing biomolecules
(proteins and peptides) to inert materials, having the creation of innovative
bio-active materials as final goal. Protocols for the visualization and im-
mobilization of proteins are given in Section 1.3.

1.2.1 Surface Functionalization
Surface functionalization strategies aim to introduce new biologically rele-
vant properties to inert materials without undermining its bulk material