Periosteum functionalized hydrogel with macroporous interpenetrating network for bone tissue engineering

• A dual-photocrosslinking macroporous hydrogel was proposed. • The hydrogel was introduced by the integration of PdECM and silk fibroin. • Macrophage polarization was regulated by the hydrogel from M1 to M2. • Periosteum functionalization facilitated the cellular osteogenic differentiation. Periosteum-derived decellularized extracellular matrix (PdECM) composed of various organized collagens and bioactive factors is deeply involved in the bone healing process. However, the ability of filling irregular defects while maintaining the structural stability remains a challenge. In this study, we successfully engineer an interconnected macroporous hydrogel by combination of silk fibroin and PdECM with photocrosslinkable interpenetrating networks. The presence of silk fibroin hydrogels increases the mechanical performance while the photoinitiator system- of tris (2,2-bipyridyl) dichlororuthenium (II) hexahydrate and sodium persulfate- endows the PdECM with prolonged stability. We demonstrate that the reinforced hydrogels facilitate the proliferation, attachment, and the differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro . Furthermore, we explore the effects of the PdECM-functionalized hydrogels on regulating macrophage fate. Our results confirm that this hydrogel is able to promote a phenotypic transition from the pro-inflammatory M1 to the pro-healing M2 phenotype. We envision that this hydrogel that offers bone regeneration microenvironments may be a promising strategy for bone tissue engineering.