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Protein bio-based hydrogels have emerged as a versatile and functional class of biomaterials due to their unique properties, including biocompatibility, biodegradability, tunable mechanical strength, and environmental responsiveness (pH, enzymes, ions and light). This review comprehensively explores the preparation methods, physicochemical properties, and multidimensional applications of protein-based hydrogels. Various fabrication techniques, such as chemical crosslinking, physical gelation, and enzymatic reactions, are discussed, highlighting their impact on the structure and functionality of hydrogels. The intrinsic properties of protein hydrogels are summarized in detail, including mechanical properties, swelling resistance, frost resistance, adhesion, biocompatibility and degradability. Furthermore, this review delves into their diverse applications, which span tissue engineering, drug delivery, wound healing, food preservation, biosensing, and environmental remediation. Finally, the challenges and future prospects of protein-based hydrogels are addressed, emphasizing the necessity for scalable production, enhanced stability, and multifunctional integration to meet the growing demands of advanced biomedical and industrial applications. This review aims to provide a comprehensive understanding of protein-based hydrogels and to inspire innovative research in this rapidly evolving field.
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http://dx.doi.org/10.1016/j.ijbiomac.2025.144199 | DOI Listing |
J Mater Chem B
September 2025
The Avram and Stella Goldstein Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel.
The development of "smart" polymers capable of responding to physiologically relevant stimuli is essential for engineering dynamic sensing and actuation systems that leverage biological signals under specific (patho)physiological conditions. In this study, we present a general and versatile strategy to engineer novel stimuli-responsive behaviors in temperature-responsive protein-based polymers (PBPs) site-specific conjugation with self-immolative molecules. Specifically, we developed hydrogen peroxide (HO)- and β-galactosidase (β-gal)-responsive elastin-like polypeptides (ELPs) and resilin-like polypeptides (RLPs).
View Article and Find Full Text PDFTherapeutic T-cell engineering from human hematopoietic stem cells (HSCs) focuses on recapitulating notch1-signaling and α4β1-integrin-mediated adhesion within the thymic niche with supportive stromal cell feeder-layers or surface-immobilized recombinant protein-based engineered thymic niches (ETNs). The relevant Notch1-DLL-4 and α4β1-integrin-VCAM-1 interactions are known to respond to mechanical forces that regulate their bond dissociation behaviors and downstream signal transduction, yet manipulating the mechanosensitive features of these key receptor-ligand interactions in thymopoiesis has been largely ignored in current ETN designs. Here, we demonstrate that human T-cell development from cord blood-derived CD34 HSCs is regulated via molecular cooperativity in notch1 and integrin-mediated mechanotransduction.
View Article and Find Full Text PDFJ Colloid Interface Sci
August 2025
Hubei Provincial Key Laboratory of Green Materials for Light Industry, Hubei University of Technology, Wuhan 430068, China. Electronic address:
Human-machine interaction (HMI) textile interfaces with safe ingredients for intelligent wearable sensing systems are critical in the era of information and the metaverse. To address the dual limitations of traditional synthetic polymer hydrogels (poor biocompatibility) and pure protein-based materials (limited mechanical performance), this study has redesigned the protein structure for a bovine serum albumin (BSA)-based composite hydrogel fibers system. By leveraging the synergistic interplay of dynamic ionic crosslinking and covalent crosslinking, the hydrogel system achieves enhancements in both mechanical strength and processability.
View Article and Find Full Text PDFSci Adv
August 2025
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Hydrogel biomaterials offer great promise for three-dimensional cell culture and therapeutic delivery. Despite many successes, challenges persist in that gels formed from natural proteins are only marginally tunable whereas those derived from synthetic polymers lack intrinsic bioinstructivity. Toward the creation of biomaterials with both excellent biocompatibility and customizability, recombinant protein-based hydrogels have emerged as molecularly defined and user-programmable platforms that mimic the proteinaceous nature of the extracellular matrix.
View Article and Find Full Text PDFFront Bioeng Biotechnol
August 2025
Department of Chemistry, Université du Québec à Montréal, Montreal, QC, Canada.
With an estimated prevalence of over two cases per 1,000 patients, chronic wounds represent a massive burden on healthcare systems around the globe. Such wounds often lead to major complications, including amputations, that greatly affect the living conditions of patients. Typical therapeutic approaches include skin grafts and topical application of therapeutic molecules such as growth factors.
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