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Engineering and characterization of a hydrogel mimicking subcutaneous interstitial space
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry. (Farmacutisk fysikalisk kemi)
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Macromolecular Chemistry.ORCID iD: 0000-0002-6977-0711
Univ Coll London UCL, Sch Pharm, 29-39 Brunswick Sq, London WC1N 1AX, England..
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Macromolecular Chemistry.ORCID iD: 0000-0001-6947-9601
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2024 (English)In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 205, article id 112739Article in journal (Refereed) Published
Abstract [en]

We have synthesized and characterized a collagen-hyaluronic acid hybrid network. The aim was to create a hydrogel mimicking the extracellular matrix of adipose tissue, primarily for use in in vitro studies of protein drug transport in the subcutaneous interstitial space. The network was created by covalently crosslinking methacryloyl-functionalized collagen type I and thiol-functionalized hyaluronic acid by means of thiol-Michael and thiol-ene photo-click reaction. The degree of modification corresponded to 74 % of the lysine and arginine groups on collagen, and 16 to 29 % of the carboxylate groups on hyaluronic acid, as determined with H-1 NMR. Circular dichroism measurements showed that the triple helix of modified collagen remained intact. Oscillatory shear rheology tests showed that the hydrated networks displayed viscoelastic properties characteristic of hydrogels. The storage modulus, measured at 1 Hz frequency in the linear viscoelastic range (<5%), varied in a controllable way between 1.5 and 4 kPa depending on the collagen concentration and collagen-to-hyaluronic acid ratio. The hydrogels had a lower collagen content (0.6--1.2 wt%) but similar hyaluronic acid content and shear modulus at low strain rates as the extracellular matrix in adipose tissue and were penetrable by albumin and lysozyme. The results show that the hydrogels are promising as model systems for investigations of drug transport.

Place, publisher, year, edition, pages
Elsevier, 2024. Vol. 205, article id 112739
Keywords [en]
Collagen, Interstitial Space, Bio mimicking hydrogels, Hyaluronic acid, Subcutaneous tissue, Parenteral delivery
National Category
Polymer Chemistry Biochemistry Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-524283DOI: 10.1016/j.eurpolymj.2023.112739ISI: 001164280100001OAI: oai:DiVA.org:uu-524283DiVA, id: diva2:1842477
Funder
Vinnova, 2017-02690Vinnova, 2019-00048Available from: 2024-03-05 Created: 2024-03-05 Last updated: 2025-02-20Bibliographically approved

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Rodler, AgnesSamanta, AyanHilborn, JönsHansson, Per

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