Biomedical Engineering Reference
In-Depth Information
a 3D structure will cause cells to form a random 2D monolayer [ 16, 18 ] . In vivo,
cells are subjected to growth in three dimensions and complex cell-cell interactions.
This observation encouraged a paradigm shift from conventional 2D cell culture
models towards 3D micro-environments [ 98 ]. To obtain a more realistic understand-
ing of cell-cell and cell-biomaterial interactions, Kirkpatrick et al. [ 99 ] proposed
the use of co-culture models in vitro. Independent of the applied strategy, the ulti-
mate goal of TE remains the same. Nevertheless, regarding the aspect of 3-dimen-
sional cell migration, proliferation and differentiation behaviour and requisites, one
can distinguish two major premises. Currently both of them are being heavily
explored. The first one is based on the presumption that cells require an assisting 3D
biomaterial scaffold that closely mimics the corresponding extracellular matrix
(ECM) [ 98, 100 ]. In this approach, the biomaterial construct acts as a necessary cell
guide and supporting template. The second one finds its roots in the hypothesis that
cells have a considerable potency to self-organize through cell-cell interactions and
is referred to as “scaffold-free TE” [ 101 ]. While the former theory maximizes the
role of a supporting structure as a cell guide and minimizes the potency to self-
assembly, the latter reverses the importance of both contributions.
9.2.2
Scaffolds
Ideally, scaffolds can be seen as ECM biomimetic structures with three main objec-
tives [ 16, 17 ]: (1) defining a space that moulds the regenerating tissue, (2) tempo-
rary substitution of tissue functions and (3) guide for tissue ingrowth. It is clear that
scaffold design should meet the needs of some basic requirements to be able to meet
those objectives, including [ 2, 14, 16- 18 ] the following: high porosity (preferably
100 % interconnectivity for optimal nutrient/waste flow and tissue ingrowth); rele-
vant geometry and pore dimensions (five to ten times the cell diameter); biodegrad-
able with adjusted degradation time; maintaining the mechanical integrity during a
prefixed time frame; it should have suitable cell-biomaterial interactions and it
should be easy to manufacture. Adjusting the mechanical and degradation proper-
ties to the desired tissue is essential. Either enzymatic or non-enzymatic hydrolytic
processes control the degradation profile. Specifically, TE requires biomaterials that
provoke cell interactions (~bioactivity) [ 102 ] and as little as possible adverse body
reactions (~biocompatibility) [ 103 ]. Control over the material bioactivity can be
achieved by incorporating growth factors [ 104 ] , enzymatic recognition sites [ 105 ] ,
adhesion factors [ 93, 106 ] or material modi fi cations [ 105 ] . Material modi fi cation is
a general term indicating either bulk modification [ 102, 107 ] or surface modi fi cation
[ 102, 108, 109 ]. Modifying the bulk properties is closely related to material bio-
compatibility, the physical and chemical properties covering the lifespan of the
implant [ 110 ], while varying the surface chemistry reflects on the initial cell/tissue-
material interactions [ 110, 111 ] .
Figure 9.1 illustrates schematically the complex multidisciplinary interac-
tions inherent towards scaffold fabrication. In the subscience of scaffolding,
Search WWH ::




Custom Search