Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation

Hong Ji Yan, Tommaso Casalini, Gry Hulsart-Billström, Shujiang Wang, Oommen Podiyan Oommen, Matteo Salvalaglio, Sune Larsson, Jöns Hilborn, Oommen P. Varghese

    Research output: Contribution to journalArticleScientificpeer-review

    39 Citations (Scopus)

    Abstract

    Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.
    Original languageEnglish
    Pages (from-to)190-202
    JournalBiomaterials
    Volume161
    DOIs
    Publication statusPublished - 3 Feb 2018
    Publication typeA1 Journal article-refereed

    Publication forum classification

    • Publication forum level 2

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