Multistage functional nanoplatform synergizing with robust wet-adhesive scaffolds for accelerated cranial bone regeneration

The healing process in cranial defects has many challenges. The disorder of the microenvironment and the long healing period posed significant complexity to the design of hydrogel scaffolds. Here, a multistage functional repair (immunomodulation/angiogenesis/osteogenesis) nanoplatform with synergistic and stable wet adhesion hydrogel scaffold was designed and developed. Cu-etched silica porous nanoparticles loaded with Mg-epigallocatechin gallate constituted the anti-inflammatory/osteogenic nanoplatform (CuSi@MgE). Dopa-modified oxidized sodium alginate and poly(thioctic acid) were combined via a hydrophobic cross-linking strategy to form a stable wet-adhesive hydrogel scaffold (TO). This innovative construct exhibited exceptional wet adhesion enabling seamless host-bone integration and resilience to intracranial pressure fluctuations, ensuring functional stability during skull repair. The TO@CuSi@MgE hydrogel demonstrated robust reactive oxygen species scavenging, antibacterial activity and macrophage M2 polarization that collectively remodeled the osteogenic immune microenvironment. At the same time, it promoted vascular regeneration and osteogenic differentiation in a phased manner, markedly sped up the healing of skull injuries.