HYBRID BIOMATERIALS FOR ENGINEERING VASCULAR TISSUES - Biologically-Responsive Hybrid Biomaterials - page 370

angiopoietin (Ang) stabilize the newly formed capillaries by recruiting pericytes
and SMCs.
The incorporation of growth factors into the scaffold material can allow
continuous stimulation of vascular tissue growth. The delivery can be classified
by the release process, which is either driven by passive diffusion or coupled to
the degradation rate of the material [60].
Various release systems of porous degradable solid scaffolds have been
formed from polyesters of lactic acid (PLA), glycolic acid (PGA) and poly
lactide-co glycolide (PLG). In one study, VEGF or FGF-1 was combined with
polymer particles prior to scaffold processing, and a sustained release of growth
factor through the degradation process was demonstrated within a short time
period [61]. To achieve a more optimized, slow release period, a further
technique was developed. This approach allowed the encapsulation of growth
factors in microspheres before scaffold processing. The combination of both
techniques achieves a more mature angiogenesis process by delivery of two or
more growth factors within one scaffold. The combination of VEGF and PDGF
shows a rapid formation of vascular networks. While VEGF was released during
the initial degradation phase and stimulated the growth of a primitive vascular
network, PDFG was subsequently released from encapsulated microspheres and
stimulated network development and support by recruiting SMCs [62].
An alternative method for angiogenic factor delivery employs the co-culture
of endothelial cells with a further cell type, such as fibroblasts or SMCs seeded
within a fibrin gel [63]. Fibroblasts act as the growth factor delivery vehicle and
participate in the stimulation and stabilization of new capillaries by the
production of TGF- Ȳ or angiopoietin.
To increase the biofunctionality of the synthetic polymers and therefore to
mimic the surrounded ECM, various strategies have been developed by attaching
specific peptides to the polymer surface. In normal tissue, the ECM is a network
of scaffolding components including different collagen types, fibronectin,
laminin, hyaluronic acid and fibrin [64]. Various ECM peptides sequences which
determine the influence of cell behavior have been grafted on synthetic materials
to enhance the biological properties. RGD peptide, a synthetic peptide from
fibronectin, has been reported to increase endothelial cell and EPC adhesion after
incorporation to polycarbonate or polyurethane [29].
Therefore, the components of ECM are obtained as naturally extracted or
chemically synthesized proteins for the purpose of augmenting the biological
properties of tissue engineering scaffolds. Cultured endothelial cells have been
shown to form capillary-like structures with lumens on collagens, fibrin,
fibronectin and laminin [65].