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

Alexandre Trubert-Paneli; Jonathan A. Williams; James F.C. Windmill; Leire Iturriaga Oñarte-Echevarria; Eonan W. Pringle; Theodora Rogkoti; Siyuan Dong; Amaia Cipitria; Aline F. Miller; Cristina Gonzalez-Garcia; Alberto Saiani; Manuel Salmeron-Sanchez

doi:10.1016/j.biomaterials.2025.123553

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

Alexandre Trubert-Paneli
, Jonathan A. Williams
, James F.C. Windmill
, Leire Iturriaga Oñarte-Echevarria
, Eonan W. Pringle
, Theodora Rogkoti
, Siyuan Dong
, Amaia Cipitria
, Aline F. Miller
, Cristina Gonzalez-Garcia
, Alberto Saiani
, Manuel Salmeron-Sanchez^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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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.

Original language	English
Article number	123553
Number of pages	14
Journal	Biomaterials
Volume	325
Early online date	11 Jul 2025
DOIs	https://doi.org/10.1016/j.biomaterials.2025.123553
Publication status	Published - 28 Feb 2026

Funding

The work was supported by funding from the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 874889 - HEALIKICK), European Research Council AdG (101054728) and EPSRC through the Transformative Healthcare Technologies Programme Grant ‘Mechanomeds’ (EP/X033554/1). C.G-G. acknowledges support from the Engineering and Physical Sciences Research Council (Grant No. EPSRC NIA – EP/T000457/1). A.T.P. acknowledges the companies Manchester BIOGEL Ltd. and Cell Guidance Systems Ltd. for their support. IBEC is member of CERCA Programme/ Generalitat de Catalunya.

Keywords

peptide hydrogels
critical sized bone defect
biomaterials

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Trubert-Paneli, A., Williams, J. A., Windmill, J. F. C., Oñarte-Echevarria, L. I., Pringle, E. W., Rogkoti, T., Dong, S., Cipitria, A., Miller, A. F., Gonzalez-Garcia, C., Saiani, A., & Salmeron-Sanchez, M. (2026). Tenascin-c functionalised self-assembling peptide hydrogels for critical-sized bone defect reconstruction. Biomaterials, 325, Article 123553. https://doi.org/10.1016/j.biomaterials.2025.123553

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title = "Tenascin-c functionalised self-assembling peptide hydrogels for critical-sized bone defect reconstruction",

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.",

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Trubert-Paneli, A, Williams, JA , Windmill, JFC, Oñarte-Echevarria, LI, Pringle, EW, Rogkoti, T, Dong, S, Cipitria, A, Miller, AF, Gonzalez-Garcia, C, Saiani, A & Salmeron-Sanchez, M 2026, 'Tenascin-c functionalised self-assembling peptide hydrogels for critical-sized bone defect reconstruction', Biomaterials, vol. 325, 123553. https://doi.org/10.1016/j.biomaterials.2025.123553

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AU - Trubert-Paneli, Alexandre

AU - Williams, Jonathan A.

AU - Windmill, James F.C.

AU - Oñarte-Echevarria, Leire Iturriaga

AU - Pringle, Eonan W.

AU - Rogkoti, Theodora

AU - Dong, Siyuan

AU - Cipitria, Amaia

AU - Miller, Aline F.

AU - Gonzalez-Garcia, Cristina

AU - Saiani, Alberto

AU - Salmeron-Sanchez, Manuel

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N2 - 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.

AB - 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.

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M1 - 123553

ER -

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

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