Spatiotemporal biomaterial functionalization via competitive supramolecular complexation of avidin and biotin analogs

T. Kamperman, M. Koerselman, C. Kelder, J. Hendriks, J.F. Crispim, X. de Peuter, P.J. Dijkstra, M. Karperien, J. Leijten

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INTRODUCTION: Native tissues are characterized by a dynamic nature. Recapitulating such dynamicity in engineered tissues requires spatiotemporal control over their biochemical composition. Here, we pioneered supramolecular desthiobiotin/avidin complexation to enable dynamic functionalization of biomaterials. Desthiobiotin is a non-sulfur containing analog of biotin that also interacts with avidin, but with substantially lower binding affinity than biotin [1]. We hypothesized that combining biotinylated hydrogel with desthiobiotinylated bioactive molecules would enable the spatiotemporal functionalization of biomaterials via in situ desthiobiotin/biotin displacement, which is a novel, facile, and fully cytocompatible material modification strategy. METHODS: Biotinylated dextran-based (Dex-TA) hydrogel constructs were functionalized with 1μM neutravidin (i.e., avidin analog), 1μM desthiobiotin-FITC (D-FITC) and 1μM biotin-atto565 (B-atto565), and subsequently analyzed using fluorescence recovery after photobleaching (FRAP) and confocal microscopy. Surface plasmon resonance imaging (SPRi) and reporter cells were used to analyze the reversible presentation and bioactivity of desthiobiotinylated BMP7 antibodies and BMP7 growth factors. RESULTS & DISCUSSION: The reversible and sequential modification of the hydrogel constructs was demonstrated by displacing D-FITC with B-atto565. By tuning the concentration and incubation time of B-atto565, we reproducibly controlled its penetration depth into the hydrogel. An injectionmolded bone-shaped 3D construct was spatially modified by controlling the thickness of the biotindisplaced layer. Moreover, competitive supramolecular complexation enabled the temporal presentation of desthiobiotinylated BMP7 antibodies and growth factors, as confirmed using SPRi and reporter cells. CONCLUSIONS: We have successfully developed and characterized a novel spatiotemporal biomaterial modification strategy based on competitive supramolecular complexation.
Original languageEnglish
Number of pages1
Publication statusPublished - 2019
EventTERMIS European Chapter Meeting 2019: Tissue Engineering Therapies: From Concept to Clinical Translation & Commercialisation - Rodos Palace, Rhodes, Greece
Duration: 27 May 201931 May 2019


ConferenceTERMIS European Chapter Meeting 2019
Abbreviated titleTERMIS EU 2019
Internet address


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