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Ll. Oliver-Cervelló, H. Martin-Gomez, M. P. Gine-bra, C. Mas-Moruno. The power of peptides to mimic bone extracellular matrix: development of a multifunctional engineered scaffold. 

Oral Presentation:
World Biomaterials Congress (WBC 2020). Dec 11th–15th, 2020. Online Conference.

ABSTRACT ➞

Mimicking bone extracellular matrix (ECM) on biomaterials is essential to regulate cell-material interactions. This may be achieved reproducing integrin and growth factor (GF) signaling. To avoid the clinical risks associated with the use of bone morphogenetic protein 2 (BMP-2), synthetic osteogenic domains may be an alternative way to promote integrin-GF signaling. Herein, we have thus identified sequences derived from the wrist and knuckle epitopes of BMP-2 and evaluated their osteogenic potential. Subsequently, the most active sequences have been combined with integrin-binding RGD peptides within an engineered biomimetic multifunctional scaffold, aiming at exploiting integrin and GF signaling. Such scaffold has been further used to functionalize titanium surfaces to recreate bone ECM. The feasibility of this strategy has been corroborated by means of cell adhesion and osteodifferentiation assays with mesenchymal stem cells (MSCs).

H. Martin-Gomez, I. Sánchez, Ll. Oliver-Cervelló, V. Marchán, C. Mas-Moruno. A click-based chemical toolkit to functionalize biomaterials. 

Oral Presentation:
World Biomaterials Congress (WBC 2020). Dec 11th–15th, 2020. Online Conference.

ABSTRACT ➞

In biomaterials science, peptides and peptidomimetics are widely used to functionalize material surfaces in order to confer bioactivity to otherwise inert substrates. The attachment of biomolecules to biomaterials is commonly achieved using specific anchors with chemical affinity for the substrates. Well-known examples include the use of thiols to bind gold substrates or catechol groups to bind titanium and other metallic oxides. However, this implies that each synthesized peptide can be used only for a narrow range of materials. Thus, in the majority of cases, changing the material of study requires synthesizing the same peptide with a distinct anchor, resulting in time-consuming and repetitive procedures. To solve this, here we report on the development of a novel and versatile click-based solid-phase synthetic strategy to prepare peptidic coatings suitable for functionalizing a variety of biomaterials (a chemical toolkit). In detail, we focused on the synthesis of a model peptide and the optimization of the copper-catalysed azide-alkyne cycloaddition reaction to introduce to the peptidic backbone distinct anchoring groups in an efficient and modular fashion. Subsequently, model substrates of different nature commonly used as biomaterials were functionalized with the peptidic toolkit by simply selecting the appropriate anchor. The feasibility of this method was validated by physicochemical surface characterization and cellular assays.

Dr. Ada Cavalcanti-Adam. Surface control of adhesion and growth factor mecha-nical and chemical cross-talk.

Keynote Lecture:
13th IBEC Symposium. Online conference: 28th October, 2020

ABSTRACT ➞

Mechanical and chemical cues present in the extracellular environment regulate cell adhesion- mediated responses, such as migration, proliferation and differentiation. To address how local changes in the extracellular environment regulate cell responses through specific receptor-ligand interactions material surfaces can be designed to combine adhesive ligands and growth factors at the nanoscale. I will present surface functionalization strategies to control integrin clustering and cellular adhesion forces. The nanoscale presentation of integrin ligands is also combined with growth factors, namely bone morphogenetic proteins (BMPs), to modulate cell osteodifferentiation. In this talk, I will also discuss the synergistic effect of BMPs and mechanical cues on osteogenic signaling and mechanotransduction, elucidating the interdependency of Smad 1/5 and YAP/TAZ signaling.

Lluis Oliver-Cervelló, H. Martin-Gómez, F. Nouredi-nne, E.A. Cavalcanti-Adam, M.P. Ginebra, C. Mas-Moruno. . The Capacity of RGD and DWIVA Peptidic Biointerface to Transdiffe-renciate C2C12 Myoblasts into Osteogenic Lineage.

Flash Presentation:
13th IBEC Symposium. Online conference: 28th October, 2020

ABSTRACT ➞

Recreating the healing microenvironment of bone tissue is particularly important to ensure the success of biomaterials. In this regard, surface biofunctionalization with integrin-binding molecules combined with growth factor derived sequences is an interesting approach. Herein, a multifunctional peptidic biointerface containing the RGD cell adhesive motif together with the DWIVA peptide (derived from the wrist epitope of BMP-2), was used to study the synergistic promotion of integrin/GF signaling on C2C12 myoblasts. Biological characterization with C2C12 myoblasts showed the potential of this biointerface to promote cell adhesion (increasing the number of attached cells and their projected area), transdifferentiation to osteogenic lineage (by inhibiting myotube formation) and BMP-2 dependent signaling through Smad independent pathway (as shown by the high expression of p38).

Dr. Nihal Engin Vrana. Personalised, multifunctio-nal coatings for medical devices against infections and adverse immune reactions.

Keynote Lecture:
Materials Science and Engineering Conference. 22-25th Sept. 2020. Originally in Darmstadt (Germany), held virtually.

ABSTRACT ➞

The personalized medicine approach has already paid dividends in patient-specific chemotherapy and other pharmaceutical applications. In the case of medical devices, the personalization is mainly based on the anatomical fit of the implants. However, the personalization of the implant interface to control better the host response to the implanted materials and also to diminish the risks such as infection is only recently come to be considered. Another important aspect is the ability to resolve several problems using only one coating. In this context, we have been developing multi-component coatings based on supramolecular assemblies where each component brings in an inherent biological activity while contributing to the physicochemical properties of the coating. As such assemblies can be produced by iterative processes, the coatings can be modified with respect to the patients' immunoprofiles. In this talk, a personalized coating development workflow including immunoprofiling and coating optimization using polypeptides and polysaccharides will be presented.

Judit Buxadera-Palomero, H. Martin-Gómez, Ll. Oliver-Cervelló, M.P. Ginebra, C. Mas-Moruno. Design of multifunctional peptide plat-forms with antimicrobial and cell adhesive properties.

Oral Presentation:
Materials Science and Engineering Conference. 22-25th Sept. 2020. Originally in Darmstadt (Germany), held virtually.

ABSTRACT ➞

Implant failure due to bacterial infection and incomplete integration represents a major issue in the fields of orthopedics and dentistry. To overcome this problem, in this study we present the design and development of peptidic platforms that simultaneously reduce bacterial adhesion while enhancing eukaryotic cell adhesion. Such dual activity is achieved by combining the human lactoferrin 1-11 peptide (Lf1-11) with the cell binding motif RGD within a branched molecular scaffold. Furthermore, the peptides contain a catechol group as anchoring unit and poly(ethylene glycol) (PEG) spacers. Different spacer lengths were studied, in order to assess the correlation between the conformation and accessibility of the peptides and the biological response. While the anchoring motif provides a single step immobilization on the titanium surface, the versatility of the synthetic routes allowed for the study of different molecular configurations. The peptidic platforms significantly improved the adhesion of human mesenchymal stem cells (MSCs) compared to control titanium, but similar values of cell adhesion were observed among all the studied peptides. Interestingly, cell spreading was higher on the surfaces coated with the peptides with a shorter spacer, indicating that above a certain level of length and flexibility of the spacer, the availability of the peptide for cell receptors is compromised. Read more...