Engineering of an osteoinductive and growth factor-free injectable bone-like microgel for bone regeneration.

Bone autografts remain the gold standard for bone grafting surgeries despite having increased donor site morbidity and limited availability. BMP-loaded grafts represent another successful commercial alternative. However, the therapeutic use of recombinant growth factors has been associated with significant adverse clinical outcomes. This highlights the need to develop biomaterials that closely approximate the structure and composition of bone autografts, which are inherently osteoinductive and biologically active with embedded living cells, without the need for added supplements. Here, we developed injectable growth factor-free bone-like tissue constructs that closely approximate the cellular, structural and chemical composition of bone autografts. We demonstrate that these micro-constructs are inherently osteogenic, and demonstrate the ability to stimulate mineralized tissue formation and regenerate bone in critical-sized defects in-vivo. Furthermore, we assessed the mechanisms that allow hMSCs to be highly osteogenic in these constructs, despite the lack of osteoinductive supplements, whereby YAP nuclear localization and adenosine signaling appear to regulate osteogenic cell differentiation. Our findings represent a step towards a new class of minimally invasive, injectable, and inherently osteoinductive scaffolds, which are regenerative by virtue of their ability to mimic the tissue cellular and extracellular microenvironment, thus showing promise for clinical applications in regenerative engineering. This article is protected by copyright. All rights reserved.