Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 66

3.4.2 Optimization of the biological component of
the prosthesis/tissue complex

These strategies utilize knowledge of cardiovascular cell biology in conjunc-
tion with material science and bioengineering to optimize tissue regenera-
tion and healing. They include the use of growth factors and other pharma-
cologic interventions to promote endothelialization, the seeding of devices
with either differentiated cells or stem cells, the use of hydrogels and poly-
mers as drug and cell delivery vehicles, and biomaterial surface modifi cation
strategies which promote cardiovascular healing.

Endothelialization

For reasons discussed earlier, the induction of endothelialization on bio-
material blood-contacting surfaces is thought to be a critical step in estab-
lishing the long-term biocompatibility of cardiovascular devices. Numerous
strategies have been employed to this end. These include the promotion of
spontaneous endothelial ingrowth by inducing EC mitogenesis and migra-
tion from edges of the device, utilizing porous biomaterials and locally
delivered pro-angiogenic growth factors to enable transmural angiogenesis
(Gosselin et al. , 1996; Tassiopoulos and Greisler, 2000; Cho et al. , 2005;
Brewster et al. , 2008) (Fig. 3.1), seeding biomaterial surfaces with autolo-
gous ECs or immune evading stem cells (Suggs and Mikos, 1999; Greisler
et al. , 1992a; Gray et al. , 1994; Gulbins et al. , 2005) and improving the adhe-
siveness of biomaterial surfaces for greater retention of transplanted ECs.
Coating of endovascular stents and vascular grafts with fi bronectin and
poly-L-lysine, or linking integrin ligand peptide sequences such as RGDV
and YIGSR, can signifi cantly increase EC adhesiveness under both static
and dynamic fl ow conditions (Jun and West, 2004; Cho et al. , 2005; Wang et
al. , 2006). ePTFE covalently linked to fi bronectin either via GA or sulfos-
uccinimidyl-4-(p-maleimidophenyl) butyrate (SMPB) has been shown to
be signifi cantly more effective in promoting cellular adhesion compared
to uncoated ePTFE. Increases in cell adhesion seen in fi bronectin-GA
linked grafts compared to fi bronectin-SPMB linked grafts were attribut-
able to increased availability of RGD binding sites in the fi bronectin-GA
group (Vallieres et al. , 2007). The alteration of electrochemical surface
properties by the implantation of negative silver ions has also been dem-
onstrated to improve the growth of ECs on artifi cial surfaces (Sato et al. ,
1999). Recent studies have investigated the targeted delivery of systemi-
cally delivered ECs transfected with superparamagnetic nanoparticles to
home ECs to metallic stents placed in the carotid artery in order to
promote the in vivo induction of device endothelialization (Polyak et al. ,
2008).

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