4D Printing of Personalized-Tunable Biomimetic Periosteum with Anisotropic Microstructure for Accelerated Vascularization and Bone Healing

An ideal biomimetic periosteum is expected to wrap various bone surfaces to orchestrate an optimal microenvironment for bone regeneration, including facilitating local vascularization, recruiting osteoblasts, and mineralizing the extracellular matrix (ECM). To mimic the role of the natural periosteum in promoting bone repair, a 4D printing technique to inlay aligned cell sheets on shape-shifting hydrogel is used, containing biophysical signals and spatially adjustable physical properties, for the first time. The outer hydrogel layer endowed the biomimetic periosteum with the ability to digitally coordinate its 3D geometry to match the specific macroscopic bone shape to maintain a bone healing microenvironment. The inner aligned human mesenchymal stem cells (hMSCs) layer not only promoted the migration and angiogenesis of co-cultured cells but also exhibited excellent osteogenic differentiation properties. In vivo experiments show that apart from morphing preset shapes as physical barriers, the aligned biomimetic periosteum can actively facilitate local angiogenesis and early-stage osteogenesis. Altogether, this present work provides a novel route to construct a personalized biomimetic periosteum with anisotropic microstructure by introducing a tunable shape to maintain the bone reconstruction microenvironment and this strategy can be extended to repair sophisticated bone defects.

Automated summary

An ideal biomimetic periosteum is developed using a 4D printing technique to inlay aligned cell sheets on shape-shifting hydrogel, mimicking the natural periosteum's role in promoting bone repair. The outer hydrogel layer allows the biomimetic periosteum to digitally coordinate its 3D geometry to match the specific bone shape, while the inner aligned hMSCs layer promotes cell migration, angiogenesis, and osteogenic differentiation. In vivo experiments demonstrate that the aligned biomimetic periosteum can actively facilitate local angiogenesis and early-stage osteogenesis, providing a novel approach for constructing personalized biomimetic periosteum and repairing complex bone defects.