Novel Peptide-Based Platform for the Dual Presentation of Biologically Active Peptide Motifs on Biomaterials

Abstract

Biofunctionalization of metallic materials with cell adhesive molecules derived from the extracellular matrix is a feasible approach to improve cell-material interactions and enhance the biointegration of implant materials (e.g., osseointegration of bone implants). However, classical biomimetic strategies may prove insufficient to elicit complex and multiple biological signals required in the processes of tissue regeneration. Thus, newer strategies are focusing on installing multifunctionality on biomaterials. In this work, we introduce a novel peptide-based divalent platform with the capacity to simultaneously present distinct bioactive peptide motifs in a chemically controlled fashion. As a proof of concept, the integrin-binding sequences RGD and PHSRN were selected and introduced in the platform. The biofunctionalization of titanium with this platform showed a positive trend towards increased numbers of cell attachment, and statistically higher values of spreading and proliferation of osteoblast-like cells compared to control noncoated samples. Moreover, it displayed statistically comparable or improved cell responses compared to samples coated with the single peptides or with an equimolar mixture of the two motifs. Osteoblast-like cells produced higher levels of alkaline phosphatase on surfaces functionalized with the platform than on control titanium; however, these values were not statistically significant. This study demonstrates that these peptidic structures are versatile tools to convey multiple biofunctionality to biomaterials in a chemically defined manner.

Antibacterial Properties of hLf1–11 Peptide onto Titanium Surfaces: A Comparison Study Between Silanization and Surface Initiated Polymerization

“…Finally, peptide attachment on the surfaces was determined by a clear increase in the percentage of carbon and nitrogen levels and a decrease in the detectable signals of titanium oxide, in comparison with control samples. In particular, an enhanced N 1s signal is attributed to amide groups of the peptide sequence 67 , as confirmed by C1s and O1s deconvolutions ( Tables 5).. However, the fact that APTES and DMPA-APMA copolymers also contain carbon and nitrogen in their structures, does not allow a direct comparison within the strategies to measure the efficiency in peptide coupling.…”

Customized Interface Biofunctionalization of Decellularized Extracellular Matrix: Toward Enhanced Endothelialization

“…32,33 The peptides were manually synthesized in solid phase (2-chlorotrityl chloride resin, 200 mg, 1.0 mmol/g) following the Fmoc/tBu strategy according to a previously reported protocol. 25 In brief, Fmoc-lamino acids were sequentially coupled at a four equivalent excess using either OxymaPure/N,N¢-diisopropylcarbodiimide (DIC) or HATU/N,N-diisopropylethylamine (DIEA) as coupling systems. 34 The efficiency of each coupling step was monitored using the Kaiser test and/or by high-performance liquid chromatography (HPLC) analysis.…”

“…25,39 Briefly, lyophilized bioactive peptides were reconstituted in PBS (pH 6.5), and dECM components were incubated for 12 h at room temperature under orbital agitation at 100 rpm in varying peptide concentrations (100, 200, and 500 mM). dECM incubated in plain PBS under the same conditions served as nonfunctionalized control.…”

“…24 Moreover, distinct bioactive peptides can be combined to exert synergistic or complementary effects on the surface of an implant. 25 Therefore, in this study, we specifically designed and synthesized custommade synthetic peptides with the following cell adhesive sequences to functionalize dECM:…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…Applications of thiol mediated modification of gold are predominately focused on analytical investigations (Huang et al, 2009;Lee et al, 2013a;Migliorini et al, 2014). Interestingly, thiols were used for the immobilization of multifunctional motifs to titaniumsurfaces as well (Mas-Moruno et al, 2013;Mas-Moruno et al, 2014). However, the interaction is probably mediated by physisorption and not by chemisorption, resulting in less affinity.…”