SYNTHESIS AND IN VITRO/IN VIVO RESPONSE TO PEPTIDEPOLYMER CONJUGATES - Biologically-Responsive Hybrid Biomaterials - page 127

contraction was observed (Figure 14). Shown in Figure 14 are the effects of
RGD-PEG sIPN + KGF, unmodified sIPN (i.e., unmodified gelatin and PEGdA
only, and no RGD-PEG), and conventional dressing, Silverlon®. While the
conventional dressing resulted in a visible depression in the healing wound, both
the unmodified sIPN and the RGD-PEG sIPN + KGF supported the formation of
tissue with no visible depression, demonstrating its structural effectiveness as a
scaffold. In addition, the RGD-PEG sIPN + KGF resulted in high levels of
macrophages and fibroblasts that were similar to undamaged tissue by three
weeks, suggesting granulation of tissue at the later stages of wound healing for
RGD-PEG sIPN + KGF treated wounds. The epidermis was restored to a thicker
degree with more ridges for the RGD-PEG sIPN + KGF treated wounds as well
as a basket-weave patterned ECM developing toward the epidermis. There were
also larger occurrences of neovascularization as well as thicker and more dense
collagen bundles in the RGD-PEG + KGF treated wounds when compared to
unmodified sIPN or conventional dressing treated wounds.
4. Host Response to Peptide-Polymer Conjugate Systems: Future Directions
and Challenges
Peptide conjugated polymer systems are a newly emerging class of biomaterials
that can combine select advantages from biological and synthetic components to
create a uniquely functionalized material. Advances in peptide conjugated
materials have been exponential and a wealth of knowledge has been gained
about the effect of peptide conjugated materials on the host response. Peptides
offer stability and specific induction of cell events, but there remains much to be
understood about the impact of these peptides' selectivity and presentation on the
biomaterial surface and how that impacts cell behavior. For example, while some
report the importance of ŋ v Ȳ 3 integrin-mediated fibroblast focal adhesion and
stress fiber formation in fibroblasts to a RGD presenting surface, others have
demonstrated the key role of Ȳ 2 containing integrins on monocyte adhesion onto
a RGD presenting surface [41-43]. It is also becoming clearer that the density of
peptides on the material plays a critical role in host response. For example, while
Massia and Hubbell reported that a RGD density of 1 fmol/cm 2 grafted on a glass
surface induced maximal fibroblast adhesion and spreading while Rowley and
Mooney showed a 30 fmol/cm 2 RGD density on an alginate surface induced
maximum myoblast adhesion and proliferation [41,44]. In addition, Sawyer and
others have demonstrated a threshold for RGD density's impact on mesenchymal
stem cells (MSC), where a high RGD concentration coated on the hydroxyapatite
surface actually deterred MSC binding and spreading [45]. However, these