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Hyaluronic Acid/Type I Collagen Hydrogels With Tunable Physicochemical Properties Using Diels–Alder Click Chemistry

2025/09/22 by Rabia Fatima, Bethany Almeida · 1 voice
Materials Science · Biochemistry, Genetics and Molecular Biology · #Silk-based biomaterials and applications #Hydrogels: synthesis, properties, applications #Collagen: Extraction and Characterization

paper · doi:10.1002/jbm.a.37992

openalex publication_date 2025/09/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/05

Abstract

Hydrogels that combine mechanical tunability with biochemical relevance are essential for engineering tissue-mimetic scaffolds for tissue engineering and regenerative medicine applications. In this study, we present for the first time a tunable hydrogel platform formed via Diels-Alder bioorthogonal click chemistry using furan-functionalized hyaluronic acid (HA-furan), furan-functionalized type I collagen (Col-furan), and bis-maleimide-functionalized polyethylene glycol (mal-PEG-mal). Hydrogels were fabricated at furan:maleimide molar ratios of 1:0.5, 1:1, and 1:2.5 and gelled under physiological conditions for 24 h without the need for catalysts or initiators. Material characterization revealed that this mechanism fabricated predominantly elastic hydrogels, where the 1:1 M ratio hydrogel was the most stable and had the highest mechanical properties, with a Young's modulus that was 2.1-fold and 4.7-fold larger than the 1:0.5 and 1:2.5 M ratio hydrogels, respectively. Further analysis revealed that hydrogel stability and performance were predominantly controlled by hydrogel structure (amorphous vs. crystalline) and crosslinking density. This enhanced mechanical stability and performance were also synergized with enhanced bioactivity from the incorporation of Col, which introduced native Arg-Gly-Asp (RGD) motifs that support cell interactions. Overall, this bioactive yet biomechanically stable hydrogel system provides a tunable platform for engineering extracellular matrix-inspired biomaterials with broad potential for soft tissue repair and regenerative medicine applications.

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