Dynamic PEG Hydrogels: From Molecular Design to Organoids and Engineered Tissues

Chien-Chi Lin, Ph.D

Abstract: Poly(ethylene glycol) (PEG)-based hydrogels are powerful platforms for engineering cell-instructive microenvironments, yet their adoption is often limited by complex, lengthy, and solvent-intensive macromer synthesis. In this seminar, I will discuss our efforts to simplify the preparation of PEG-norbornene (PEGNB) without compromising the rapid, tunable network crosslinking, and cytocompatibility that make click hydrogels attractive for cell manufacturing, organoid engineering, and controlled delivery. Our early work established thiol-norbornene photopolymerization as a cytocompatible step-growth strategy that rapidly forms well-defined PEG networks, supports encapsulation of sensitive cells, and enables enzymatic recovery of functional multicellular spheroids. Systematic studies then revealed how network connectivity, crosslinker chemistry, peptide sequence, pH, and ester hydrolysis govern degradation, providing design rules for tunable gel degradation. Building on these principles, we replaced pungent norbornene acid and multistep organic synthesis with carbic anhydride-based routes that shortened reaction time, reduced hazardous solvent use, and ultimately enabled aqueous and microwave-assisted synthesis. These streamlined macromers retained efficient thiol-norbornene and inverse electron-demand Diels-Alder click crosslinking while expanding hydrogel functionality through programmable degradation from hours to months, long-term hydrolytic stability, on-demand photodegradation, and digital light processing (DLP) printability. The resulting materials have enabled rapidly dissolvable microgel templates for macroporous cell-laden matrices, injectable hydrogels, multimodal controlled-release systems, and sacrificial bioinks for advanced fabrication. Collectively, this body of work demonstrates that simplifying and greening macromer synthesis need not sacrifice material performance. Instead, accessible and scalable chemistry can preserve, and in some cases expand, the crosslinking, degradation, fabrication, and biological capabilities of dynamic PEG hydrogels, broadening their utility for stem cell culture, tissue and organoid engineering, regenerative medicine, controlled delivery, and disease modeling.

Bio: Dr. Chien-Chi Lin is a Professor in the Weldon School of Biomedical Engineering at Purdue University. He earned his PhD in Bioengineering from Clemson University and completed postdoctoral training in the laboratory of Dr. Kristi Anseth at the University of Colorado Boulder. He also holds BS and MS degrees in Chemical Engineering from National Tsing Hua University and National Taiwan University, respectively. Dr. Lin’s interdisciplinary research integrates materials science and engineering, bioconjugation chemistry, and cancer and stem cell biology. His contributions have been recognized with numerous honors, including Outstanding Graduate Student Awards from Clemson University, the American Institute of Chemists Postdoctoral Award, the Georgia Tech Frontiers in Bioengineering Young Investigator Award, the NSF Faculty Early Career Development (CAREER) Award, an invitation to the National Academy of Engineering Frontiers of Engineering Symposium, and the Abraham M. Max Distinguished Professor Award from the Purdue School of Engineering and Technology. He has also served as an Honorary Scientist and Advisor on Agricultural Science and Technology for the Rural Development Administration of the Republic of Korea. In 2024, Dr. Lin was elected a Fellow of the American Institute for Medical and Biological Engineering (AIMBE). He has published more than 100 peer-reviewed articles, and his research has received continuous federal support since 2011 from agencies including the National Institutes of Health, National Science Foundation and U.S. Army, as well as support from foundations, industry partners, and international agencies.