An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis

Limited stem cells and mismatched interface fusion have plagued biomaterial-mediated cranial reconstruction. Here, the authors engineer an instantly fixable and self-adaptive scaffold to promote calcium chelation and interface integration, regulate macrophage M2 polarization, and recruit endogenous stem cells. Limited stem cells, poor stretchability and mismatched interface fusion have plagued the reconstruction of cranial defects by cell-free scaffolds. Here, we designed an instantly fixable and self-adaptive scaffold by dopamine-modified hyaluronic acid chelating Ca2+ of the microhydroxyapatite surface and bonding type I collagen to highly simulate the natural bony matrix. It presents a good mechanical match and interface integration by appropriate calcium chelation, and responds to external stress by flexible deformation. Meanwhile, the appropriate matrix microenvironment regulates macrophage M2 polarization and recruits endogenous stem cells. This scaffold promotes the proliferation and osteogenic differentiation of BMSCs in vitro, as well as significant ectopic mineralization and angiogenesis. Transcriptome analysis confirmed the upregulation of relevant genes and signalling pathways was associated with M2 macrophage activation, endogenous stem cell recruitment, angiogenesis and osteogenesis. Together, the scaffold realized 97 and 72% bone cover areas after 12 weeks in cranial defect models of rabbit (phi = 9 mm) and beagle dog (phi = 15 mm), respectively.

Automated summary

In this study, an instantly fixable and self-adaptive scaffold was engineered to promote cranial reconstruction by calcium chelation and interface integration, while also regulating macrophage M2 polarization and recruiting endogenous stem cells.