Intrafibrillar Crosslinking Enables Decoupling of Mechanical Properties and Structure of a Composite Fibrous Hydrogel

Abstract

The fibrous network of an extracellular matrix (ECM) possesses mechanical properties that convey critical biological functions in cell mechanotransduction. Engineered fibrous hydrogels show promise in emulating key aspects of ECM structure and functions, however, varying hydrogel mechanics without changing its architecture remains a challenge. We developed a composite fibrous hydrogel to vary gel stiffness without affecting structure by controlling intrafibrillar crosslinking. The hydrogel was formed from aldehyde‐modified cellulose nanocrystals and gelatin methacryloyl (GelMA) that provided the capability of intrafibrillar photocrosslinking. By varying the degree of gelatin functionalization with methacryloyl groups and/or photoirradiation time, we changed the hydrogel's elastic modulus by more than an order of magnitude, while preserving the fiber diameter and pore size. The hydrogel was used to seed primary mouse lung fibroblasts and test the role of ECM stiffness on fibroblast contraction and activation. Increasing hydrogel stiffness by stronger intrafibrillar crosslinking resulted in enhanced fibroblast activation and increased fibroblast contraction force, yet at reduced contraction speed. The developed approach enables the fabrication of biomimetic hydrogels with decoupled structural and mechanical properties, facilitating studies of the influence of tissue‐like ECM mechanics on tissue development and disease progression.This article is protected by copyright. All rights reserved

Photo-cross-linked Hydrogels for Cartilage and Osteochondral Repair

“…142 In addition to 3D printing, the integration of novel technologies, such as electrospinning, with photo-cross-linked hydrogels exhibits significant potential for various applications. 143,144 The utilization of electrospinning to fabricate GelMA leads to remarkable properties such as elevated strength and toughness. This combination effectively compensates for the inherent limitations of the gel and is expected to be realized in cartilage tissue engineering.…”

In situ forming an injectable hyaluronic acid hydrogel for drug delivery and synergistic tumor therapy

“…Natural polysaccharides have received significant attention for applications of biomedical carrier materials (e.g., hyaluronic acid (HA), sodium alginate, chitosan, cellulose and gelatin) due to multiple functional groups modified in various ways to change characteristics [ [14] , [15] , [16] , [17] , [18] ]. The chemical modification of functional groups is the key issue to control the structural properties of hydrogel, including stability, mechanical properties and biodegradation [ 19 ]. The modification methods of polysaccharides mainly include sulfation, carboxymethylation, acetylation, etc.…”

Hybrid hydrogel-extracellular matrix scaffolds identify distinct ligand and mechanical signatures in cardiac aging

“…In most scaffold platforms, tuning mechanical properties will alter the ligands and/or architecture. A handful of novel material systems have been described that are capable of independent tunability [13][14][15] , yet the incorporation of native ECM properties is still lacking. Thus, our mechanistic understanding of the specific contributions stemming from ECM cues is currently limited.…”