Tenascin-c functionalised self-assembling peptide hydrogels for critical-sized bone defect reconstruction

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Trubert-Paneli, Alexandre and Williams, Jonathan A. and Windmill, James F.C. and Oñarte-Echevarria, Leire Iturriaga and Pringle, Eonan W. and Rogkoti, Theodora and Dong, Siyuan and Cipitria, Amaia and Miller, Aline F. and Gonzalez-Garcia, Cristina and Saiani, Alberto and Salmeron-Sanchez, Manuel (2026) Tenascin-c functionalised self-assembling peptide hydrogels for critical-sized bone defect reconstruction. Biomaterials, 325. 123553. ISSN 1878-5905 (https://doi.org/10.1016/j.biomaterials.2025.123553)

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Abstract

Critical-sized bone defects cannot heal spontaneously and receive poor clinical prognosis due to limitations in modern treatment strategies. Next-generation therapies are applying biomaterials incorporating BMP-2 to effectively promote and support bone regeneration, but adverse effects are linked to uncontrolled BMP-2 egress from the biomaterial. Implementing extracellular matrix proteins to biomaterials is a favourable approach to alleviate these drawbacks, and self-assembling peptide hydrogels are rapidly emerging as modulable and versatile biomaterials. Here, we describe the creation of a tenascin-c-functionalised peptide hydrogel designed to regenerate critical-sized bone defects. A recombinant fragment of tenascin-c spanning from the 3rd to 5th fibronectin-like domains is integrated into the fibre network. We demonstrate that this nascent construct effectively retains BMP-2 to differentiate mesenchymal stem cells into mature osteoblasts and achieves complete unionisation of murine critical-sized bone defects under low BMP-2 dose. All in all, we demonstrate tenascin-c as a suitable candidate to functionalise biomaterials intended for bone engineering applications and the promising potential of self-assembling peptide hydrogels in treating critical-sized bone defects.

ORCID iDs

Trubert-Paneli, Alexandre, Williams, Jonathan A. ORCID logoORCID: https://orcid.org/0000-0002-9828-4886, Windmill, James F.C. ORCID logoORCID: https://orcid.org/0000-0003-4878-349X, Oñarte-Echevarria, Leire Iturriaga, Pringle, Eonan W., Rogkoti, Theodora, Dong, Siyuan, Cipitria, Amaia, Miller, Aline F., Gonzalez-Garcia, Cristina, Saiani, Alberto and Salmeron-Sanchez, Manuel;
CORE (COnnecting REpositories)