Modular peptides promote human mesenchymal stem cell differentiation on biomaterial surfaces

Abstract

Summary Molecular design strategies in biomedical applications often involve creating modular “fusion” proteins, in which distinct domains within a single molecule can perform multiple functions. We have synthesized a new class of modular peptides that include a biologically active sequence derived from the growth factor BMP-2 and a series of hydroxyapatite-binding sequences inspired by the N-terminal α-helix of osteocalcin. These modular peptides can bind in a sequence-dependent manner to the surface of “bone-like” hydroxyapatite coatings, which are nucleated and grown on a biodegradable polymer surface via a biomimetic process. The BMP2-derived sequence of the modular peptides is biologically active, as measured by its ability to promote osteogenic differentiation of human mesenchymal stem cells. Our study indicates that the modular peptides described here are multifunctional, and the characteristics of this approach suggest that it can potentially be applied to a range of biomaterials for regenerative medicine applications.

Controlled Multiple Growth Factor Delivery from Bone Tissue Engineering Scaffolds via Designed Affinity

“…The affinity of this engineered peptide was characterized previously by Lee et al and is due to the presence of an osteocalcin-inspired peptide sequence containing three g-carboxylated glutamic acid resides that coordinate with calcium ions in the mineral crystal lattice. 42 Previous studies have demonstrated an ability to systematically vary the peptide-mineral binding affinity and release. 42,43 Here, we chose to use the highest affinity mineral-binding sequence to extend mBMP release over a much longer time frame than rhVEGF release, as a clear demonstration of our dual release concept.…”

“…42 Previous studies have demonstrated an ability to systematically vary the peptide-mineral binding affinity and release. 42,43 Here, we chose to use the highest affinity mineral-binding sequence to extend mBMP release over a much longer time frame than rhVEGF release, as a clear demonstration of our dual release concept. Analysis of the release profile of the growth factors from mineral-coated b-TCP biomaterials showed that both rhVEGF and mBMP can be released for over 60 days in different mediums (Fig.…”

Anti‐fibrosis effect of BMP‐7 peptide functionalization on cobalt chromium alloy

“…26 When immobilized, they were reported to have release kinetics for 40 days 37 up to 70 days. 38 Site-specific immobilization of peptides also protects against invasive ectopic bone formation, high-local concentrations in the microenvironments, and the problems associated with undesirable effects at locations beyond the implant site. 37 Therefore, the immobilized BMP-7 peptide at the metal surface has the benefit of restricting fibroblasts attachment, proliferation, and fibrosis gene expression, hence improving implant integration.…”

“…As the peptide is securely bound to the substrates via covalent bioconjugation, there is no release of the peptide to the culture medium. 37,38 The use of this chemical conjugation process will result in the creation of strong covalent bonds and intermolecular interactions between the metallic substrates and the peptide. On the one hand, these intermolecular bonds of the coating cannot be easily disrupted by normal mechanical forces 39 encountered.…”

Enhancement of the Regenerative Potential of Anorganic Bovine Bone Graft Utilizing a Polyglutamate-Modified BMP2 Peptide with Improved Binding to Calcium-Containing Materials

“…Examples of such domains include bisphosphonates [39][40][41][42] as well as sequences comprised of negatively charged amino acids, including glutamate, aspartate, or the noncanonical amino acids, gcarboxyglutamate and phosphoserine. [15][16][17]19,23,25,[43][44][45] For delivery of bioactive peptides, polyglutamate or polyaspartate domains offer some advantages over other types of calciumbinding modules. Aspartate and glutamate residues are readily available, and the polyglutamate/polyaspartate motifs can be synthesized as contiguous sequence with the bioactive part of the peptide using a commercial peptide synthesizer.…”