Protease-degradable hydrogels with multifunctional biomimetic peptides for bone tissue engineering

Lluís Oliver-Cervelló; Helena Martin-Gómez; Cristina Gonzalez-Garcia; Manuel Salmeron-Sanchez; Maria-Pau Ginebra; Carlos Mas-Moruno

doi:10.3389/fbioe.2023.1192436

Protease-degradable hydrogels with multifunctional biomimetic peptides for bone tissue engineering

Front Bioeng Biotechnol. 2023 Jun 1:11:1192436. doi: 10.3389/fbioe.2023.1192436. eCollection 2023.

Authors

Lluís Oliver-Cervelló^{1

2}, Helena Martin-Gómez^{1

2}, Cristina Gonzalez-Garcia³, Manuel Salmeron-Sanchez³, Maria-Pau Ginebra^{1

2

4}, Carlos Mas-Moruno^{1

2}

Affiliations

¹ Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain.
² Barcelona Research Center in Multiscale Science and Engineering, UPC, Barcelona, Spain.
³ Centre for the Cellular Microenvironment, Advanced Research Centre, University of Glasgow, Glasgow, United Kingdom.
⁴ Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.

Abstract

Mimicking bone extracellular matrix (ECM) is paramount to develop novel biomaterials for bone tissue engineering. In this regard, the combination of integrin-binding ligands together with osteogenic peptides represents a powerful approach to recapitulate the healing microenvironment of bone. In the present work, we designed polyethylene glycol (PEG)-based hydrogels functionalized with cell instructive multifunctional biomimetic peptides (either with cyclic RGD-DWIVA or cyclic RGD-cyclic DWIVA) and cross-linked with matrix metalloproteinases (MMPs)-degradable sequences to enable dynamic enzymatic biodegradation and cell spreading and differentiation. The analysis of the intrinsic properties of the hydrogel revealed relevant mechanical properties, porosity, swelling and degradability to engineer hydrogels for bone tissue engineering. Moreover, the engineered hydrogels were able to promote human mesenchymal stem cells (MSCs) spreading and significantly improve their osteogenic differentiation. Thus, these novel hydrogels could be a promising candidate for applications in bone tissue engineering, such as acellular systems to be implanted and regenerate bone or in stem cells therapy.

Keywords: DWIVA; biomimetic peptides; functionalization; hydrogel; multifunctionality; osteogenic differentiation.

Grants and funding

This work was supported by the Spanish State Research Agency (PID 2020-114019RB-I00/AEI/10.13039/501100011033), the AGAUR (2021 SGR 01368 and FI-2018 predoctoral fellowship of LO-C) and the Generalitat of Catalunya (ICREA Academia Award of MP-G). This work has also received funding from the European Union’s Horizon 2020 research and innovation Programme under the Marie Sklodowska-Curie Grant Agreement No. 872869 (project Bio-Tune, RISE).