Biomedical Engineering Reference
In-Depth Information
oligopeptides for the formation of polymer networks. For that purpose, vinyl
sulfonate-functionalized multiarm telechelic PEG macromers were converted
with the thiolate units of various cystein-containing peptides [115]. The cre-
ation of synthetic ECM analogs, in which ligand type, concentration and spa-
tial distribution can be modulated upon a passive background was shown to
help in deciphering the complexity of signaling in cell-ECM interactions. For
instance, the suitability of proteolytically degradable synthetic poly(ethylene
glycol) (PEG)-based hydrogels as an ECM model system for cell migration re-
search was recently tested and compared with the two well-established ECM
mimetics fibrin and collagen. The study shows that the high protease sensi-
tivity makes PEG hydrogels an interesting model system that allows a direct
correlation between protease activity and cell migration [116]. Also, the util-
ity of integrating two types of protein signals into such networks has been
demonstrated by combining oligopeptides mediating cell adhesion and sub-
strates for cellular-controlled degradation to engineer bone [117]. Further
relevant studies on the combination of peptides with synthetic polymer struc-
tures concern work to clarify the impact of the ligand density required for
a particular cellular response [118], nanoscale spatial organization of adhe-
sion ligands [119], the relevance of ligand gradients [120] and studies on the
coregulation of signals [121]. Mooney and coworkers reported about a single
matrix capable of delivering multiple growth factors (VEGF and PDGF) with
distinct kinetics which dramatically increased blood vessel maturity [122].
While the above systems employ a synthetic polymer as the main compon-
ent which is decorated with biomimetic peptides a rather different type of
biohybrid matrix uses biopolymers as the main component which is further
modified in order to exhibit certain desired characteristics. This approach
has been elaborated in quite some detail for fibrin, the polymerized form of
fibrinogen (see above). For example, an engineered variant form of VEGF
that mimics matrix-binding and cell-mediated release by local cell-associated
enzymatic activity was bound to fibrin with the result that the quality of an-
giogenesis in the matrix was substantially improved [123].
In view of these examples joint efforts of matrix biology and polymer sci-
ence towards novel biohybrid matrices with tissue specific or morphogenetic
signaling characteristics seem to be within in reach. Future work will have to
elaborate this idea in the branches of regenerative therapies, namely stem cell
bioengineering and in vivo tissue engineering, using the principles described
above.
References
1. Wassarman P, Miner J (2005) Extracellular Matrix in development and disease: ad-
vances in developmental biology, vol 15. Elsevier, Amsterdam
2. Kreis T, Vale R (1993) Extracellular matrix and adhesion proteins. Oxford University
Press, Oxford
