Silicate biomaterials modulate heart-bone paracrine interactions for tissue repair

Abstract

The repair of tissue injuries involving complex inter-tissue interactions remains challenging because conventional biomaterials are usually designed to target individual tissues. This study focuses on heart-bone paracrine interactions and proposes a biomaterial-based strategy to modulate reciprocal communication between cardiac- and bone-related cells for tissue repair. We show that strontium silicate (SS) biomaterials release bioactive Sr²⁺ and Si species that promote the functional activation of encapsulated CMs and bone marrow stromal cells, while also reshaping their secretory profiles. Using 3D-bioprinted co-culture models and local implantation in rodent injury models, we demonstrate that SS-modulated BMSC-laden constructs promote cardiac repair after myocardial infarction, whereas SS-modulated CM-laden constructs enhance cranial bone regeneration. Mechanistically, these effects are associated with altered secretion of candidate paracrine factors, including IGF-1, SDF-1, and BMP-2, and functional involvement of PI3K/AKT and MAPK/ERK signaling pathways. These findings suggest that silicate biomaterials may act as upstream regulators of heart-bone paracrine interactions by combining transient ionic stimulation with secondary remodeling of cellular secretory profiles. This study provides a proof-of-concept strategy for biomaterial-regulated inter-tissue communication and tissue repair.

Statement of significance

This study introduces the concept of using silicate biomaterials to facilitate beneficial communication between the heart and bone for coordinated repair. We demonstrate that strontium silicate releases bioactive ions and modulates key signaling factors (SDF-1, IGF-1, BMP-2), activating PI3K/AKT and MAPK/ERK pathways. This not only enhances cardiac function recovery but also promotes bone healing in rat disease models. To our knowledge, this is the first report demonstrating a single biomaterial orchestrating multi-organ interactive repair by targeting inter-organ crosstalk.