Biomedical Engineering Reference
In-Depth Information
scaffolds using most of the biomaterials presented in Section 14.2; porous
hydroxyapatite, porous calcium phosphate and silk fibroin nets (Unger
et al
.,
2007). the vascularisation potential of these biomaterials for bone repair was
tested in the presence of angiogenic stimuli by cell culture systems including
human dermal microvascular endothelial cells (HDMEC). HDMEC did not
migrate to form microcapillary-like structures as they did on cell culture plastic.
in co-cultures of HDMEC and primary human osteoblast cells or the human
osteoblast-like cell line MG-63 on these biomaterials, cells assembled into an
organised tissue-like structure, the endothelial cells forming microcapillary-
like structures containing a lumen and giving strong PECaM-1 expression.
These microcapillary-like structures infiltrated osteoblast cell layers and
did not form when exogenous angiogenic stimuli were added to these co-
cultures. The life span of HDMEC was also significantly enhanced by the
co-culture. These data raise important questions concerning the exact nature
of pro-angiogenic drug- or gene-delivery systems to be incorporated into
scaffolds which has to take into account the production of growth factors
by invading mesenchymal cells.
Despite the wide choice of biomaterials and techniques to engineer 3D
scaffolds, two main limitations have not yet been overcome:
∑
in most of the cases, uniform cell seeding throughout the scaffold is
difficult to achieve and, in the majority of the cases, cells sitting at the
periphery of the scaffold proliferate more quickly, generating a layer of
tissue that impedes the diffusion of nutrients and gases as well as the
elimination of cell activity by-products. As a consequence, the viability
of the cells which are located in the core of the material is impaired.
Dynamic methods such as that indicated above may improve cell
distribution throughout the material mesh, but not necessarily improve
the viability of the cells at the scaffold core.
∑
the need for a macroporous structure that can facilitate tissue in-growth
may not offer the ideal microenvironment for the cells. indeed, cells
adhering to the surface of a macropore recognise that surface as two-
dimensional (2D) rather than 3D. This situation does not reflect the true
ECM environment which surrounds cells in a natural tissue. For this
reason, it is envisaged that although macroporous scaffolds are required
to favour tissue deposition at macroscopic scale, the early phases of
the tissue repair process need to be induced by the optimisation of cell
encapsulation milieus. the development of bioresponsive hydrogels like
those described in the section entitled 'Biomineralisation molecules'
are a significant step forward in this direction and their combination
with macroporous scaffolds may result in optimal conditions for tissue
formation.
For those applications where bone repair is pursued by
in vitro
tissue
