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.

人类骨骼干细胞 (hSSC) 及其后代在骨缺损中的维持是一项重大挑战。在这里，我们报告了一种包含三维 Wnt 诱导成骨组织模型 (WIOTM) 的可移植绷带。这种绷带促进了 hSSCs（8 周）及其后代的长期生存能力，并能够在具有临界尺寸颅骨缺损的体内小鼠模型中进行骨修复。新形成的骨骼在结构上与成熟的皮质骨相当，由人类和小鼠细胞组成。此外，我们表明 WIOTM 形成的机制受 Wnt 介导的 hSSC 不对称细胞分裂的控制。将 Wnt 共价固定到合成材料上可以极化单个分裂的 hSSC，定向纺锤体并同时生成 Wnt 近端 hSSC 和分化倾向的 Wnt 远端细胞。