Bioactive Surface Modification of Metal Oxides via Catechol-Bearing Modular Peptides: Multivalent-Binding, Surface Retention, and Peptide Bioactivity

Abstract

A series of multivalent dendrons containing a bioactive osteogenic growth peptide (OGP) domain and surface-binding catechol domains were obtained through solid phase synthesis, and their binding affinity to hydroxyapatite, TiO2, ZrO2, CeO2, Fe3O4 and gold was characterized using a quartz crystal microbalance with dissipation (QCM-d). Using the distinct difference in binding affinity of the bioconjugate to the metal oxides, TiO2-coated glass slides were selectively patterned with bioactive peptides. Cell culture studies demonstrated the bioavailability of the OGP and that OGP remained on the surface for at least 2 weeks under in vitro cell culture conditions. Bone sialoprotein (BSP) and osteocalcein (OCN) markers were upregulated 3-fold and 60-fold, respectively, relative to controls at 21 days. Similarly, 3-fold more calcium was deposited using the OGP tethered dendron compared to TiO2. These catechol-bearing dendrons provide a fast and efficient method to functionalize a wide range of inorganic materials with bioactive peptides and have the potential to be used in coating orthopaedic implants and fixation devices.

MicroRNA-mediated signal amplification coupled with GNP/dendrimers on a mass-sensitive biosensor and its applications in intracellular microRNA quantification

“…Besides, its low cost, real time output, and label-free entities also attracted researchers' interests (Cheng et al, 2012). QCM has been successfully used in various biological analyses to study interactions between biomolecules Takahashi et al, 2012;Patel et al, 2009), biomolecules and abiotic molecules (Tang et al, 2014;Nelson et al, 2015;Kim et al, 2015), because of the capability to monitor the interactions in a dynamic, label-free, and noninvasive way (Takahashi et al, 2009; Uludag and Tothil, 2012). The assay is mainly implemented by detecting the frequency change before and after the target biomolecules reacted with the corresponding ligands immobilized on QCM surfaces, and the change is usually limited.…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…Incubation of coated titanium-plates in cell supernatant at 37°C displayed a remained surface coverage of around 80% over 7 days (Pagel et al, 2016). Other investigations demonstrated a half-life of 14 days on titanium in buffer and at room temperature (Tang et al, 2014). Furthermore, cell-repellent properties of DOPA-modified PEG-coatings were stable over 14 days, highlighting the strong anchorage under cell culture conditions (Dalsin et al, 2003).…”

“…These rather small molecules can be synthesized in a tailor-made way to realize directed immobilization and multifunctionality (Delaittre et al, 2012). Thereby, immobilization anchors such as thiols (Huang et al, 2009), DOPA (Tang et al, 2014;Pagel et al, 2016), phosphonic acids (Auernheimer et al, 2005), nucleic acids (Michael et al, 2009) and basic amino acids (Harris et al, 2004;Hassert et al, 2012) are easily introduced or ligated to bioactive peptides. Moreover, additional cell-attracting or repelling functionalities can be easily incorporated by specific reactions.…”

“…Two different approaches are mainly used to apply mussel adhesive properties in the field of biomaterials. On the one hand, modular peptides containing DOPA can be synthesized and easily modified by solid phase peptides synthesis (SPPS) (Ceylan et al, 2012;Ham et al, 2013;Tang et al, 2014). On the other hand, DOPA is incorporated into polymers or recombinantly expressed proteins (mussel foot proteins from the blue mussel (Mytilus edulis) by enzymatic hydroxylation of tyrosine residues (Hwang et al, 2007).…”

Multiscale approach for the construction of equilibrated all-atom models of a poly(ethylene glycol)-based hydrogel

“…[3][4][5] In recent applications, these hydrogels have been covalently tethered with bioactive peptides as side chains to mimic the biological activity provided by the extracellular matrix or growth factors, thus providing the potential for cell signaling to mediate a desired biological response. [6][7][8][9][10] In order for these materials to function as desired, it is essential that the bioactive agents contained within the hydrogel matrix be presented in a manner that provides for their accessibility and structural integrity for cell-receptor binding. While bioactivity can be experimentally probed by an appropriate set of assays, experimental methods alone are quite limited in terms of their ability to interpret the molecular basis for measured differences in bioactivity for different hydrogel compositions and designs.…”