Polyisocyanide-based hydrogels to target fibrosis:from drug screening to therapeutics

Wednesday 6 September 2023, 10:30 am
PhD student
J. Kumari MSc.
dr. P.H.J. Kouwer
dr. ir. F.A.D.T.G. Wagener

Polyisocyanide (PIC) hydrogels are a relatively new class of synthetic hydrogels that mimic the physical properties of the native extracellular matrix (ECM) properties, making PIC suitable for different biological applications. The hydrogel has highly tailorable properties, allowing functionalization with any growth factor or peptide. In this thesis, we studied the response of PIC hydrogels in models of scarring and fibrosis. We developed a high-throughput gel-contraction model to prescreen drugs for putative antifibrotic properties. This 3D in-vitro model maintained the native in-vivo phenotype and functionality of primary patient cells in contrast to the collagen-coated 2D cultures, which quickly lost their in-vivo phenotype. Our work opens the possibility of personalized medicine by testing what drugs work best to halt fibrosis in the patient’s cells. 

We also altered the properties of the hydrogel by changing the polymer conditions and by crosslinking it to other polymers. In one of the studies, an antifibrotic hydrogel prepared by crosslinking PIC with hyaluronic acid (HA). In another study, a conductive PIC hydrogel was developed by physically mixing PIC with water-soluble conductive poly(aniline-co-N-(4-sulfophenyl)aniline) (PASA). Incorporating PASA into the PIC hydrogel enhances the electroactive nature of our hydrogel without changing the fibrous architecture and (nonlinear) mechanics of PIC polymers. 

Jyoti Kumari received Bachelor of Science (B.Sc.) degree with Botany honors, from Banaras Hindu University, India in 2008. She obtained her Master of Science (M.Sc.) degree in Biotechnology from Bangalore University, India in 2010. After that she started working in Jubilant Biosys Limited, Bangalore, India for two years. In 2013, she joined as a research associate at the department of Biological Sciences and Bioengineering at the IIT, Kanpur, India. Her research focused on developing an in-vitro/ in-vivo model (publications: 3 first-author papers, 1 co-author, and 1 patent). In 2018 she started her PhD in the field of tissue engineering and biomaterial synthesis at Radboud University in collaboration with Radboud University Medical Center (UMC). During her four years of PhD she had successfully established the Polyisocyanide hydrogel as a drug screening model and for therapeutics applications.