Biomedical Engineering Reference
In-Depth Information
of artificial vessels. Fibroblast growth factors, FGF-1 (or aFGF) and FGF-2
(or bFGF), are mainly applied to induce host EC proliferation, migration and
differentiation, and eventually finalize EC reoccupation for in situ vascular
formation on man-made devices. The coordination of FGF promoters and
EC-produced proteolytics plays an essential role for angiogenesis by mod-
ulating vascular ECM and enabling EC development. As artificial scaffolds,
combinations of collagen/fibrin and collagen/PET have been designed and
developed. Equivalent to biological scaffolds like elastins of native vessels,
the artificial implants also take care of physical support and structure main-
tenance. Provisionally successful trials have been performed in vivo with
animal models [109-112].
1.5
Surface Immobilization of Proteinic Affinity Ligands
1.5.1
Surface Bioconjugation
In order to achieve biological hybridization on polymeric implants, bioactive
factors must be introduced onto biomaterial surfaces. Since the largest family
of bioactive factors is proteinic affinity ligands, protein-targeted bioconjugate
techniques have been well developed. Protein immobilization can be per-
formed by physical or chemical means, as well as some newly invented elec-
trochemical (like ionization) and physicochemical (like self-assembly mono-
layer) methods. Physical approaches are relatively simple in process with
the mechanism focusing on arranged adsorption. Variable strategies have
been utilized including electrostatic assembly, Van der Waals interaction,
H-bonding incorporation, and hydrophilic/hydrophobic affinities. However,
the drawbacks are lack of persistence and also vulnerability by variation of
conditions. In contrast, chemical conjugation resolves immobilizing stability
by covalent bonding.
The covalent surface immobilization of proteins is usually performed with
two steps: substrate (surface) activation and protein-substrate conjugation.
The targets of activation on the substrate surface are reactive groups like
hydroxyl [- OH], amine [- NH], carbonyl [C
=
O] or carboxyl [COOH]. If
these groups are intrinsically absent in the substrate material, a surface
pre-treatment must be carried out to generate them by oxidization, radi-
ation, hydrolysis, thiolysis, amination or aminolysis, etc. Sometimes, addi-
tional grafting of more specifically functional units, such as (meth)acryloyl
[CH
2
=
C - CO](forfreeradicaladdition)orvinylsulfone[CH
2
=
CH - SO
2
]
(for hydrosulphonyl addition), is also required. On most occasions, the ac-
tivated substrate covalently connects with the proteins via their pendant
amines (mostly provided by lysine, arginine, histidine moieties or side-chain
N-termini) or carboxyl (mostly provided by aspartic acid moieties or side-
