Tuning Bulk Hydrogel Degradation by Simultaneous Control of Proteolytic Cleavage Kinetics and Hydrogel Network Architecture

ACS Macro Letters
Christopher M MadlSarah C Heilshorn

Abstract

Degradation of three-dimensional hydrogels is known to regulate many cellular behaviors. Accordingly, several elegant approaches have been used to render hydrogels degradable by cell-secreted proteases. However, existing hydrogel systems are limited in their ability to simultaneously and quantitatively tune two aspects of hydrogel degradability: cleavage rate (the rate at which individual chemical bonds are cleaved) and degraded hydrogel architecture (the network structure during degradation). Using standard peptide engineering approaches, we alter the proteolytic kinetics of the polymer cleavage rate to tune gel degradation time from less than 12 h to greater than 9 days. Independently, we vary the cross-linker functionality to achieve network architectures that initially have identical molecular weight between cross-links but upon degradation are designed to release between 5% and 100% of the polymer. Confirming the biological relevance of both parameters, formation of vascular-like structures by endothelial cells is regulated both by bond cleavage rate and by degraded hydrogel architecture. This strategy to fine-tune different aspects of hydrogel degradability has applications in cell culture, regenerative medicine, and drug...Continue Reading

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Citations

Jan 9, 2020·Journal of the Royal Society, Interface·Pallavi MadhusudananSahadev Shankarappa
Jul 10, 2019·Matrix Biology : Journal of the International Society for Matrix Biology·Arturo Ibáñez-FonsecaJosé Carlos Rodríguez-Cabello
Feb 2, 2021·ACS Biomaterials Science & Engineering·Ross C Bretherton, Cole A DeForest
Nov 1, 2020·Biomaterials·Wissam FarhatAlexandra Fuchs
Sep 1, 2019·Nature Reviews. Materials·Michael J KratochvilSarah C Heilshorn
Feb 2, 2021·Current Opinion in Biomedical Engineering·Hyun KimSyam P Nukavarapu
May 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yao JiangLiangfang Zhang
Mar 25, 2021·MSystems·Maria Teresa Orozco-HidalgoCaroline M Ajo-Franklin
May 1, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zhaoyuan GuoJing Xie
Jun 23, 2021·Essays in Biochemistry·Alessia LongoniKhoon S Lim
Jan 20, 2021·ACS Biomaterials Science & Engineering·Zezhao QinXiaoniu Yang
Jul 24, 2020·Biomacromolecules·Yulia ShmidovRonit Bitton
Aug 28, 2020·Biomacromolecules·Miguel González-PérezJosé Carlos Rodríguez-Cabello
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Dec 30, 2021·The Journal of Physical Chemistry. B·Vaibhav Palkar, Olga Kuksenok
Dec 23, 2021·Advanced Healthcare Materials·Katherine L WileyApril M Kloxin
Jan 29, 2022·ACS Biomaterials Science & Engineering·Dong LiXuesi Chen

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