Mohamed Amine Mezour's research while affiliated with McGill University and other places

The durability and long-term success of metallic implants are enhanced through the molecular scale design of biocompatible and corrosion resistant surface coatings. To pursue this hypothesis, we have developed a new class of organic-inorganic (O-I) hybrid nanocomposite coatings based on tetramethylorthosilicate (TMOS) and γ-methacryloxypropyltrimethoxysilane (MAPTMS) as organofunctional alkoxysilanes precursors and dimethyltrimethylsilylphosphite (DMTMSP) as a phosphorus precursor. Addition of DMTMSP to TMOS-MAPTMS hybrids increased the extent of intermolecular condensation and cross-linking observed. Both normal human osteoblast in-vitro biocompatibility and corrosion resistance were enhanced in coatings containing DMTMSP. Though increasing phosphorous content correlated with biocompatibility, a compromise in the amount of phosphorus incorporated would be required if corrosion resistance was the most desirable parameter for optimization, at least for single coat systems. Evaluation of the electrochemical behaviour and the in-vitro biocompatibility show that films prepared using these materials by dip coating onto Ti6Al4V alloys offer a promising alternative to simpler coatings and wholly metallic prostheses.

The bone regenerative capacity of synthetic calcium phosphates (CaPs) can be enhanced through the enrichment with selected metal trace ions. However, defining the optimal elemental composition required for bone formation is challenging due to a large number of possible concentrations and combinations of these elements. We hypothesized that the ideal elemental composition exists in the inorganic phase of the bone extracellular matrix (ECM). To study our hypothesis, we first obtained natural hydroxyapatite through the calcination of bovine bone, which was then investigated its reactivity with acidic phosphates to produce CaP cements. Bioceramic scaffolds fabricated using these cements were assessed for their composition, properties, and in vivo regenerative performance and compared to controls. We found that natural hydroxyapatite can react with phosphoric acid to produce CaP cements with biomimetic trace metals. These cements present significantly superior in vivo bone regenerative performance compared to cements prepared using synthetic apatite. In summary, this study opens new avenues for further advancements in the field of CaP bone biomaterials by introducing a simple approach to develop biomimetic CaPs. This work also sheds light on the role of the inorganic phase of bone and its composition in defining the regenerative properties of natural bone xenografts.

Immunomodulation strategies are believed to improve the integration and clinical performance of synthetic bone substitutes. One potential approach is the modification of biomaterial surface chemistry to mimic bone extracellular matrix (ECM). In this sense, we hypothesized that coating synthetic dicalcium phosphate (DCP) bioceramics with bone ECM proteins would modulate the host immune reactions and improve their regenerative performance. To test this, we evaluated the in vitro proteomic surface interactions and the in vivo performance of ECM-coated bioceramic scaffolds. Our results demonstrated that coating DCP scaffolds with bone extracts, specifically those containing calcium-binding proteins, dramatically modulated their interaction with plasma proteins in vitro, especially those relating to the innate immune response. In vivo, we observed an attenuated inflammatory response against the bioceramic scaffolds and enhanced peri-scaffold new bone formation supported by the increased osteoblastogenesis and reduced osteoclastogenesis. Furthermore, the bone extract rich in calcium-binding proteins can be 3D-printed to produce customized hydrogels with improved regeneration capabilities. In summary, bone extracts containing calcium-binding proteins can enhance the integration of synthetic biomaterials and improve their ability to regenerate bone probably by modulating the host immune reaction. This finding helps understand how bone allografts regenerate bone and opens the door for new advances in tissue engineering and bone regeneration. Statement of Significance: Foreign-body reaction is an important determinant of in vivo biomaterial integration, as an undesired host immune response can compromise the performance of an implanted biomaterial. For this reason, applying immunomodulation strategies to enhance biomaterial engraftment is of great interest in the field of regenerative medicine. In this article, we illustrated that coating dicalcium phosphate bioceramic scaffolds with bone-ECM extracts, especially those rich in calcium-binding proteins, is a promising approach to improve their surface proteomic interactions and modulate the immune responses towards such biomaterials in a way that improves their bone regeneration performance. Collectively, the results of this study may provide a conceivable explanation for the mechanisms involved in presenting the excellent regenerative efficacy of natural bone grafts.

Oral hygiene and regular maintenance are crucial for preserving good peri‐implant health. However, available prophylaxis products and toothpastes, which are optimized for cleaning teeth, tend to contaminate and abrade implant surfaces due to their organic components and silica microparticles, respectively. This study aims to develop an organic‐free implant‐paste based on two‐dimensional nanocrystalline magnesium phosphate gel and hydrated silica nanoparticles (20–30% w/w) for cleaning oral biofilm on titanium dental implants. The surface chemistry, morphology, and bacterial load of contaminated Ti disks before and after decontamination using prophylaxis brushing with toothpaste and implant‐paste were characterized by X‐ray photoelectron spectroscopy (XPS), scanning electron microscopy, and fluorescence spectroscopy. Both commercial toothpastes and implant‐paste remove bacteria, however, only implant‐paste protects Ti metal from abrasion and removes organic contaminants. XPS showed a significant decrease of carbon contamination from 73% ± 2 to 20% ± 2 after mechanical brushing with implant‐paste compared to 41% ± 11 when brushing with commercial toothpastes (p < 0.05). Fluorescence microscopy revealed that bacteria load on biofilm contaminated Ti (44 × 103 ± 27 × 103/µm2) was significantly reduced with the implant‐paste to 2 × 103 ± 1 × 102/µm2 and with a commercial toothpaste to 2.9 × 103 ± 7·102/µm2. This decay is relatively higher than the removal achieved using rotary prophylaxis brush alone (5 × 103 ± 1 × 103/µm2, p < 0.05). Accordingly, this novel implant‐paste shows a great promise as an efficient decontamination approach. © 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018.

Biomedical and dental prostheses combining polymers with metals often suffer failure at the interface. The weak chemical bond between these two dissimilar materials can cause debonding and mechanical failure. This manuscript introduces a new mechanical interlocking technique to strengthen metal/polymer interfaces through optimized additively manufactured features on the metal surface. To reach an optimized design of interlocking features, we started with the bio-mimetic stress-induced material transformation (SMT) optimization method. The considered polymer and metal materials were cold-cured Poly(methyl methacrylate) (PMMA) and laser-sintered Cobalt-Chromium (Co-Cr), respectively. Optimal dimensions of the bio-inspired interlocking features were then determined by mesh adaptive direct search (MADS) algorithm combined with finite element analysis (FEA) and tensile experiments such that they provide the maximum interfacial tensile strength and stiffness while minimizing the stress in PMMA and the displacement of PMMA at the Co-Cr/PMMA interface. The SMT optimization process suggested a Y-shape as a more favorable design, which was similar to mangrove tree roots. Experiments confirmed that our optimized interlocking features increased the strength of the Co-Cr/PMMA interface from 2.3 MPa (flat interface) to 34.4±1 MPa, which constitutes 85% of the tensile failure strength of PMMA (40.2±1 MPa). Statement of significance: The objective of this study was to improve metal/polymer interfacial strength in dental and orthopedic prostheses. This was achieved by additive manufacturing of optimized interlocking features on metallic surfaces using laser-sintering. The interlocking design of the features, which was a Y-shape similar to the roots of mangrove trees, was inspired by a bio-memetic optimization algorithm. This interlocking design lowered the PMMA displacement at the Co-Cr/PMMA interface by 70%, enhanced the interfacial strength by more than 12%, and increased the stiffness by 18% compared with a conventional bead design, meanwhile no significant difference was found in the toughness of both designs.

Tailoring the surface chemistry of CoCr alloys is of tremendous interest in many biomedical applications. In this work, we show that CoCr can be modified by diazonium electrografting provided the surface is not homogeneously covered with an oxide layer. Cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) show the electrografting of a poly(aminophenylene) (PAP) layer on CoCr when treated at a reductive potential (CoCr−0.5 V), whereas no PAP film was formed on CoCrOCP and CoCr1 V, treated at open circuit and anodic potentials respectively. Based on XPS results, we attributed the electrografting to the formation of carbide bonds between PAP and the inhomogeneous thin oxide layer of CoCr−0.5 V. We then show an example of application of PAP coatings on CoCr and prove that the presence of a PAP coating on CoCr−0.5 V results in a 5-fold increase of the adherence of poly methyl methacrylate (PMMA) to PAP-coated CoCr compared to uncoated samples; this is of prime significance to improving the long-term stability of dental prostheses. These findings support the importance of reducing the oxide layer for effective functionalization of metal oxides with aryl diazonium salts and suggest a promising surface modification approach for biomedical applications.

Statement of significance: It is remains unclear why natural teeth, unlike titanium dental implants, promote the formation of an epithelial seal that protects them against the external environment. This study used a surface screening approach to analyze the adsorption of proteins produced by epithelial tissues onto tooth-dentin and titanium surfaces, and correlate it with the behaviour of cells. This study shows that tooth-dentin, in particular its proteins, has a higher selective affinity to certain adhesion proteins, and subsequently allows more favourable interactions with epithelial cells than titanium. This knowledge could help in developing new approaches for re-establishing and maintaining the epithelial seal around teeth, and could pave the way for developing implants with surfaces that allow the formation of a true epithelial seal.