Silk-Hyaluronic Acid Composite Hydrogels for Soft Tissue Engineering
Raia, Nicole.
2019
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Hydrogels are
crosslinked polymeric networks with high water content with unique interest for soft
tissue engineering due to their similarity to native tissue properties and potential for
injectability. This work focuses on the development and characterization of
silk-hyaluronic acid (HA) composite hydrogels for soft tissue engineering and
augmentation. The combination of silk and HA allows ... read morefor a highly tunable biomaterial,
overcoming the limitations of single component hydrogels. The majority of this research
utilized enzymatically crosslinked silk-HA hydrogels, where tyrosine residues of silk
and tyramine residues of tyramine-substituted HA were covalently crosslinked using
horseradish peroxidase and H2O2. The inclusion of HA with the silk hydrogel resulted in
decreased gelation times, increased in vitro degradation rates, and reduced changes in
mechanical properties and water retention over time. Silk-HA hydrogels were utilized in
studies for cervical augmentation as an alternative treatment to prevent preterm birth.
In order to assess the augmentation capabilities of the hydrogels, an ex vivo
pregnant-like tissue model was first developed by softening human cervical tissue from
non-pregnant patients by disrupting collagen organization via collagenase. Utilizing
this tissue model, silk-HA hydrogels showed potential for augmenting cervical tissue
without excessive stiffening. The silk-HA hydrogel system was further developed for use
as vitreous humor substitutes. A range of optically clear hydrogels with tunable
mechanics and swelling properties was obtained by altering silk/HA ratios and
crosslinking densities. In general, the results showed that decreasing crosslinking
density decreased initial shear storage modulus and increased swelling, with higher silk
ratios showing a significant increase in modulus after 1 month. Another approach in soft
tissue augmentation is the utilization of particle-hydrogel suspensions to enhance
tissue ingrowth of dermal fillers. For this approach, silk particles suspended in an HA
hydrogel carrier was used, where the effect of particle size was studied in an in vivo
model in terms of mechanical properties, degradation and biological responses. The
inclusion of particles provided increased cellular and tissue infiltration with no
decrease in volume after 6 months. Overall, this research provides an understanding of
the physicochemical and biological properties of silk-HA composite hydrogels and their
utility for soft tissue engineering.
Thesis (Ph.D.)--Tufts University, 2019.
Submitted to the Dept. of Biomedical Engineering.
Advisor: David Kaplan.
Committee: Qiaobing Xu, Michael House, and Devang Shah.
Keyword: Biomedical engineering.read less - ID:
- 7d2796753
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