Hybrid Nanotopographical Surfaces Obtained by Biomimetic Mineralization of Statherin‐Inspired Elastin‐Like Recombinamers

Abstract

Modification of surfaces mimicking unique chemical and physical features of mineralized tissues is of major interest for obtaining biomaterials for replacing and regenerating biological tissues. Here, human salivary statherin-inspired genetically engineered recombinamers (ELRs, HSS) on biomedical surfaces regulates mineralization to form an amorphous-calcium-phosphate (ACP) layer that reproduces the original substrate nanotopography. The HSS-ELRs carry a statherin-derived peptide with high affinity to tooth enamel. They are tethered to nanorough surfaces and mineralized using an enzyme-directed process. A homogeneous layer of ACP-minerals forms on HSS-coated surfaces retaining the original nanotopography of the substrate. In contrast, biomineralization of control surfaces results in uncontrolled growth of minerals. This suggest the statherin-inspired ELRs have ability to induce and control growth of the minerals on the biofunctional surfaces. Likely, the HSS-ELR coating have similar bioactivity to that of statherin in human saliva. The hybrid nanorough surfaces improve adhesion and differentiation of preosteoblasts and show potential for dental and orthopedic implants integration. This method enables the combination and tailoring of nanotopographical and biochemical cues to design functionalized surfaces to investigate and potentially direct the stem cell fate.

Mineralization and bone regeneration using a bioactive elastin-like recombinamer membrane

“…These results are consistent with studies demonstrating the affinity of the SN A 15 fragment to adsorb to hydroxyapatite surfaces by chelation with surface cal-cium ions in vitro [37]. This affinity depends on the number and close vicinity of the negatively charged residues in the N-terminal domain, as demonstrated by studies using the individual SN A 15 sequence [33] and within our HAP ELR molecule on titanium sur-faces [38]. Therefore, it is possible that the mineralization observed on our HAP membranes was produced by the high density of negative charges present on the N-terminal segment of the SN A 15 fragment of our HAPcontaining ELRs.…”

“…Rat MSCs obtained following a procedure described previously [38], were cultured on membranes made of IK and HAP ELR molecules comprising or not channels topographies. Cells were incubated overnight prior the application of the mechanical stimulation (Section 2.4) for 2 days.…”

Self‐Assembled Proteins and Peptides as Scaffolds for Tissue Regeneration

“…Of note, nonspecific protein attachment was significantly lower in the coated surfaces compared to the bare metal surface, and the surfaces with covalently attached ELPs showed higher stability than the ones with physisorbed ELPs, suggesting their suitability to improve implant biocompatibility . ELPs targeted for calcium deposition, were designed by incorporating the 15aa sequence DDDEEKFLRRIGRFG from the human salivary peptide statherin (which has high affinity for hydroxyapatite) with the basic building blocks VPGIG and VPGKG (Figure A). These ELPs were covalently attached through the lysine residue to titanium surfaces that were previously etched with alkali and silanized.…”

“…These ELPs were covalently attached through the lysine residue to titanium surfaces that were previously etched with alkali and silanized. The functionalized surfaces were able to nucleate deposition of amorphous calcium phosphates and these mineralized surfaces further supported and enhanced attachment and differentiation of a preosteoblast cell line . Cell attachment motifs such as RGDS or REDV were combined with the aforementioned calcium mineralizing sequences within the same ELR in order to test any synergistic effects towards bone regeneration applications.…”

Peptide-functionalized zirconia and new zirconia/titanium biocermets for dental applications

“…17 One of the approaches used in dentistry to covalently immobilize biomolecules on inorganic materials involves methodologies based on silane-chemistry. [18][19][20] Biomolecules with varied complexities like arginine-glycin-aspartate (RGD) sequence , 21,22 other oligopeptides, 23,24 proteins, [25][26][27] aptamers, 28 recombinamers 13,29 or even multiple peptides with cooperative activities 30 have been tethered to metal surfaces using silanes as coupling agents. We have extended this approach to develop mechanically and thermochemically stable biofunctional coatings on titanium which resist surgical shear stresses during implantation as well as the challenging bioenvironments derived from the contact with physiological fluids.…”