3D bioprinted functional scaffold based on synergistic induction of iprf and laponite exerts efficient and personalised bone regeneration via MiRNA-mediated TGF-β/Smads signaling.

Abstract

Background: Limited stem cells, low vascularization efficiency and weak osteoinductive activity plague the repair and reconstruction of bone defects with cell-free scaffolds.

Methods: Herein, injectable platelet-rich fibrin (i-PRF) was loaded into a methacrylated alginate/gelatin-methylcellulose (AGM) bioink system and constructed a porous hydrogel scaffold by three-dimensional bioprinting. The addition of nanosilicate-laponite (Lap) further enhanced this scaffold and synergized with i-PRF to promote efficient and personalized cranial regeneration.

Results: At the biochemical level, Lap significantly enhanced the ability of the scaffold to retard growth factor release, and multiple physiologically proportional growth factors in the scaffold synergistically promoted rapid neoangiogenesis and concomitantly recruited endogenous BMSCs. More importantly, the bioactive ions released by Lap markedly promoted the proliferation of BMSCs and consistently induced the osteogenic differentiation of BMSCs; At the immunological level, iPRF-AGM@Lap significantly attenuates the inflammatory response by promoting macrophage M2 polarization. Mechanistically, miRNA sequencing and functional validation experiments demonstrated that bioactive ions released by Lap could synergize with growth factors in iPRF to promote osteogenic differentiation of BMSC through the miR-21 and miR-125a-mediated TGF-β/Smads signaling pathway.

Conclusion: The results of this study provide a new idea for the personalized treatment of bone defects.