Raman Spectroscopy: A Tool for Tissue Engineering - Emerging Raman Applications and Techniques in Biomedical and Pharmaceutical Fields - page 419

meanwhile, generally require long data collection times to obtain sucient
signal-to-noise ratios, thereby limiting their suitability in the analysis of live
cell culture systems (for further details refer to the following reviews, FT-
Raman [13], RRS [14], SERS [15], CARS [16]).

18.2 Material Characterisation

18.2.1 Materials in Tissue Engineering

Numerous materials have been used in TE and a tremendous variety of tech-
niques have been used to modify the surface properties of these materials
to promote biocompatibility and induce tissue formation. Material surface
properties can be modified by physicochemical modification, topographical
surface structuring and biofunctionalisation, to promote specific protein and
desirable cellular responses. Cell behaviour, for example, has been known to
be influenced by micro- and nanoscale surface topographical features [17] and
the geometric/spatial arrangement of chemical moieties [18]. Raman spectro-
scopic characterisation of biomaterial surfaces is a well-established technique
for a variety of TE materials, including bioactive glasses, ceramic materials,
carbon fibres/carbon nanotubes, polymers, hydrogels and bioresorbable com-
posites [19-21].

18.2.2 Biofunctionalisation of Materials

Biofunctionalisation of materials is a common strategy in TE to promote se-
lective protein and cell adhesion (in vitro or following implantation in vivo).
Specific bioactive molecules such as enzymes, peptides and cell receptor lig-
ands (often ECM elements) are immobilised onto material surfaces and/or in-
tegrated within the materials for their controlled exposure. These biomolecules
can be simply adsorbed on the material's surface or covalently linked via chem-
ical groups previously created on the surface. The biological response to the
material-bound biomolecules depends upon many parameters including their
spatial distribution, density, steric hindrance, co-localisation with synergistic
ligands and structural conformation to maintain the exposure of cell-binding
domains [2]. Raman spectroscopy could offer some much-needed insight in the
characterisation of these parameters.
Raman spectroscopy has been successfully used to detect nanomolar con-
centrations of biologically relevant molecules, to distinguish between struc-
turally similar peptides (e.g. V

1 integrins [22]) and also to detect
peptide S-nitrosylation and phosphorylation [23, 24]. Raman spectroscopy
has been used to determine the functionalisation of carbon nanotubes and
other particles with bioactive peptides (e.g. RGD), whereby their biofunc-
tionalisation has enabled their accumulation at specific sites (e.g. tumours)
within small animal models [25]. Furthermore, the in vivo distribution and

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