Characterization and chemical modifications of silk fibroin hydrogels towards advanced biomaterial scaffolds
McGill, Meghan.
2019
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Hydrogels fabricated
from naturally-derived silk fibroin (SF) proteins have exciting applications in drug
delivery and regenerative medicine. SF is an excellent biomaterial due to its resilient
material properties, ability to be processed into a variety of formats, and
biocompatibility. However, the historically empirical design of SF hydrogels and a lack
of biological epitopes limit its ... read morepotential as an advanced, functional biomaterial. The
goal of this work was to enable the rational design of SF hydrogels with tunable matrix
properties, and to establish a facile and versatile method for incorporating functional
peptides into SF hydrogels. Towards this goal, fundamental characterization of SF
hydrogels was first carried out to relate crosslink density, modulus, and diffusivity to
the reactant conditions. This work introduced new characterization techniques for the
heterogeneous hydrogel matrix and showed that SF hydrogels have tunable crosslink
densities. Next, peptides containing terminal tyrosine groups were grafted onto tyrosine
residues in the SF backbone via enzymatic reaction, and the concentration, size, and
hydrophilicity of the peptides were varied. The reaction efficiency and spatial
distribution of the peptides were studied, as well as their effect on SF self-assembly,
hydrogel reaction kinetics, and modulus. SF hydrogels were then conjugated to peptides
containing a cell-binding domain and seeded with primary human fibroblasts. This work
established enzymatic crosslinking as a viable and modular method for conjugating
peptides to SF hydrogels. In a separate effort, porous and flexible SF-based splints
were developed to treat pediatric tracheomalacia and tested in a pilot preclinical
study. The results showed that splint placement decreased tracheal collapse, and there
was evidence of cellular infiltration into the splint by 24 days post operation. We
expect that this work will increase our fundamental understanding of SF hydrogels and
self-assembly, and improve the biological functionality of SF hydrogels, ultimately
expanding the potential applications for advanced silk-based
biomaterials.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Qiaobing Xu, Ayse Asatekin, and Jeannine Coburn.
Keywords: Biomedical engineering, and Materials Science.read less - ID:
- 44558s78n
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