Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair

Wnt3a protein has been immobilized on a biocompatible bandage and is now shown to induce oriented asymmetric cell division of human skeletal stem cells and can also promote bone tissue repair in vivo. The maintenance of human skeletal stem cells (hSSCs) and their progeny in bone defects is a major challenge. Here, we report on a transplantable bandage containing a three-dimensional Wnt-induced osteogenic tissue model (WIOTM). This bandage facilitates the long-term viability of hSSCs (8 weeks) and their progeny, and enables bone repair in an in vivo mouse model of critical-sized calvarial defects. The newly forming bone is structurally comparable to mature cortical bone and consists of human and murine cells. Furthermore, we show that the mechanism of WIOTM formation is governed by Wnt-mediated asymmetric cell division of hSSCs. Covalently immobilizing Wnts onto synthetic materials can polarize single dividing hSSCs, orient the spindle and simultaneously generate a Wnt-proximal hSSC and a differentiation-prone Wnt-distal cell. Our results provide insight into the regulation of human osteogenesis and represent a promising approach to deliver human osteogenic constructs that can survive in vivo and contribute to bone repair.

Automated summary

The Wnt3a protein immobilized on a biocompatible bandage induces directed asymmetric cell division of human skeletal stem cells and promotes bone tissue repair. The transplantation of a bandage containing a Wnt-induced osteogenic tissue model facilitates long-term viability of hSSCs and their progeny, resulting in bone repair in a mouse model of critical-sized calvarial defects. This approach provides insights into human osteogenesis regulation and offers a promising method for delivering human osteogenic constructs for in vivo survival and contribution to bone repair.