Engineering scaffolds to augment the repair of hard-to-soft multitissue musculoskeletal tissue units, such as bone-tendon, to simultaneously support tissue healing and functional movement has had limited success. Overcoming this challenge will require not only precise spatial control of bone- and tendon-like biomechanical properties, but also consideration of the resultant biomechanical cues, as well as the embedded biochemical cues imparted by these scaffolds. Here, we report on the effects of a spatially engineered combination of stiffness and growth factor (GF) cues to control bone-tendon-like differentiation in vitro and tissue formation in vivo. This was achieved using mechanically graded, bone- and tendon-like QHM polyurethane (QHM: Q: Quadrol; H: hexamethylene diisocyanate; M: methacrylic anhydride) scaffolds selectively biopatterned with osteogenic bone morphogenetic protein-2 (BMP-2) and tenogenic fibroblast growth factor-2 (FGF-2). First, material characterization, including porosity, surface roughness, contact angle, and microindentation measurements, was performed. Second, in vitro studies demonstrated that increased material stiffness promoted GF-mediated osteoblast differentiation and reduced tenocyte differentiation. Sustained GF exposure masked this stiffness effect. Third, in vivo studies involving subcutaneous implantation of mechanically graded and biochemically patterned QHM scaffolds (composed of these bone- and tendon-promoting GFs biopatterned on biphasic bone and tendon biomechanically mimicking regions) in mice demonstrated spatial control of bone- and tendon-like tissue formation. Altogether, these data provide new insights for future engineering of scaffolds to augment hard-to-soft multitissue repair.

工程支架以增加对难以软化的多组织肌肉骨骼组织单位（例如骨腱）的修复，以同时支持组织愈合和功能性运动，取得了有限的成功。克服这一挑战将不仅需要精确控制骨和肌腱样生物力学特性的空间，还需要考虑所得的生物力学线索以及这些支架赋予的嵌入式生化线索。在这里，我们报道了在空间上设计的刚度和生长因子（GF）提示的组合的效果，以控制体外的骨腱样分化和体内的组织形成。这是使用机械分级的，骨骼状和肌腱状的QHM聚氨酯（QHM：Q：Quadrol； H：六亚甲基二异氰酸酯； M：甲基丙烯酸酐）支架选择性地与成骨性骨形态发生蛋白2（BMP-2）和肌腱成纤维细胞生长因子2（FGF-2）进行生物模式结合。首先，进行材料表征，包括孔隙率，表面粗糙度，接触角和微压痕测量。其次，体外研究表明，增加的材料硬度可促进GF介导的成骨细胞分化并减少肌腱细胞分化。持续的GF暴露掩盖了这种僵硬效应。第三，体内研究涉及在小鼠中皮下植入机械分级和生化图案化的QHM支架（由生物仿制在双相骨和肌腱生物力学模拟区域上的这些促进骨骼和肌腱的GF组成），证明了对骨骼和肌腱样组织的空间控制编队。共，