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 3^rd to 5^th 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.