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Published on: January 14, 2020
Antifibrotic properties of hyaluronic acid crosslinked polyisocyanide hydrogels
Jyoti Kumari1, Roel Hammink2, Jochem Baaij3
1Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands; Department of Dentistry - Orthodontics and Craniofacial Biology, Radboud University Medical Centre, 6525 EX Nijmegen, the Netherlands.
Abstract:
Fibrosis is characterized by the formation of fibrous connective tissue in response to primary injury. As a result, an affected organ may lose part of its functionality due to chronic, organ-specific tissue damage. Since fibrosis is a leading cause of death worldwide, targeting fibrotic diseases with antifibrotic hydrogels can be a lifesaving therapeutic strategy. This study developed a novel hybrid antifibrotic hydrogel by combining the synthetic polyisocyanide (PIC) with hyaluronic acid (HA). Gels of PIC are highly tailorable, thermosensitive, and strongly biomimetic in architecture and mechanical properties, whereas HA is known to promote non-fibrotic fetal wound healing and inhibits inflammatory signaling. The developed HA-PIC hybrids were biocompatible with physical properties comparable to those of the PIC gels. The antifibrotic nature of the gels was assessed by 3D cultures of human foreskin fibroblasts in the presence (or absence as control) of TGFβ1 that promotes differentiation into myofibroblasts, a critical step in fibrosis. Proliferation and macroscopic contraction assays and studies on the formation of stress fibers and characteristic fibrosis markers all indicate a strong antifibrotic nature of HA-PIC hydrogel. We showed that these effects originate from both the lightly crosslinked architecture and the presence of HA itself. The hybrid displaying both these effects shows the strongest antifibrotic nature and is a promising candidate for use as in vivo treatment for skin fibrosis.
Insights
This study introduces a novel antifibrotic hydrogel combining polyisocyanide (PIC) and hyaluronic acid (HA). This hybrid hydrogel shows significant potential for treating skin fibrosis by inhibiting key fibrotic processes.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Fibrosis, characterized by excessive fibrous connective tissue, impairs organ function and is a leading global cause of mortality.
- Current therapeutic strategies for fibrotic diseases remain limited, necessitating the development of novel treatments.
- Antifibrotic hydrogels offer a promising avenue for therapeutic intervention in fibrotic conditions.
Purpose of the Study:
- To develop and characterize a novel hybrid antifibrotic hydrogel.
- To investigate the antifibrotic properties of the hybrid hydrogel in vitro.
- To evaluate the potential of the HA-PIC hydrogel for treating skin fibrosis.
Main Methods:
- Synthesis and characterization of a hybrid hydrogel composed of polyisocyanide (PIC) and hyaluronic acid (HA).
- Assessment of hydrogel biocompatibility and physical properties.
- In vitro evaluation using 3D fibroblast cultures stimulated with TGFβ1 to induce fibrotic responses.
- Analysis of fibroblast proliferation, matrix contraction, stress fiber formation, and fibrosis marker expression.
Main Results:
- The developed HA-PIC hybrid hydrogel is biocompatible and possesses suitable physical properties.
- The HA-PIC hydrogel demonstrated significant antifibrotic effects in vitro, inhibiting fibroblast differentiation and matrix deposition.
- Both the unique crosslinked architecture of PIC and the presence of HA contributed to the observed antifibrotic activity.
- The hybrid hydrogel showed a stronger antifibrotic effect compared to individual components.
Conclusions:
- The novel HA-PIC hybrid hydrogel exhibits potent antifibrotic properties.
- The combination of PIC and HA synergistically enhances antifibrotic efficacy.
- This hybrid hydrogel is a promising candidate for in vivo treatment of skin fibrosis and potentially other fibrotic diseases.
