Material-driven fibronectin assembly enables low-dose BMP-2 to regenerate structurally mature bone in critical-sized load-bearing defects
Year: 2026
Type: preprint
Abstract: Bone grafts for critical-sized load-bearing defects are usually judged by how much bone forms, and rarely by whether that bone is structurally and mechanically competent. Here, degradable ceramic monetites coated with poly(ethyl acrylate) (PEA) and functionalised with fibronectin (FN) and rhBMP-2 at 10-25 μg/mL, 60-150-fold below the approved clinical concentration, are assessed across length scales. MicroCT showed that only monetites functionalised with rhBMP-2 bridged the defect, with a significant increase in new bone volume in both the monetite vicinity and the whole defect volume. In contrast, platelet-rich plasma (PRP) functionalisation significantly reduced bone formation relative to FN, showing that the identity of the adhesion cue, and not merely its presence, determines the outcome. Monetite degradation and increased interconnected porosity favoured bone ingrowth and produced a continuous interface between monetite and new bone. The multiscale analyses of quantitative polarised light microscopy, SAXS and nanoindentation show that PEA-coated monetites functionalised with FN and 25 μg/mL rhBMP-2 promoted structurally and mechanically more mature bone, with a hierarchical organisation and local mechanical properties approaching those of native cortical tissue. In the bridged region this group recapitulated the preferential collagen fibre orientation of native cortical bone and reached an elastic modulus and hardness that were not statistically distinguishable from it, although mineral particles throughout the regenerated tissue remained thicker and less aligned than in cortical bone. Synchrotron microCT in an ovine model extended these findings to a clinically relevant scale, supporting the translational potential of the system. Taken together, these findings position PEA-coated monetites functionalised with FN and low-dose rhBMP-2 as a strategy for the structural and functional regeneration of large bone defects.
Authors: Oihane Mitxelena-Iribarren, Emma Muinos-Lopez, Leire Iturriaga, Irati Aiestaran-Zelaia, Daniel Werner, Jonathan Anthony Williams, Vineetha Jayawarna, Penelope Monica Tsimbouri, Tania Lopez-Martinez, Rafael Llombart- Blanco, Oliver Spaeker, Laura Zorzetto, Wolfgang Wagermaier, Sophie Anuth, Jussi-Petteri Suuronen, Timm Weitkamp, Bernhard Hesse, Peter Geoffrey Childs, Stuart Reid, Eva Gonzalez-Lavado, Diana Martinez-Redondo, Matthew Dalby, Froilan Granero-Molto, Manuel Salmeron-Sanchez, Amaia Cipitria
Institutions: Biogipuzkoa Health Research Institute, Navarre Institute of Health Research, Clinica Universidad de Navarra, Max Planck Institute of Colloids and Interfaces, University of Strathclyde, University of Glasgow, University of the Basque Country, Synchrotron SOLEIL, Institució Catalana de Recerca i Estudis Avançats, Barcelona Institute of Science and Technology, Institute for Bioengineering of Catalonia, Ikerbasque
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
Funders: Ministerio de Ciencia, Innovación y Universidades, Centres de Recerca de Catalunya, Equipex, European Commission, Agence Nationale de la Recherche, Fundación Científica Asociación Española Contra el Cáncer, Generalitat de Catalunya, Ikerbasque, Basque Foundation for Science, Ministerio de Ciencia e Innovación, Diputación Foral de Gipuzkoa, European Regional Development Fund, Agencia Estatal de Investigación
OpenAlex ID: W7225139685