Niche-inspired collagen infused melt electrowritten scaffolds for craniofacial bone regeneration

Advances in tissue engineering are focused on devising improved therapeutics to reconstruct craniofacial bones. In cell-based strategies, biomaterials with specific physicochemical properties can mimic natural environments, supporting stem cell renewal, survivability, and cell fate. This study highlights the engineering of a 3D-printed (Melt Electrowritten, MEW) fluorinated‑calcium phosphate (F/CaP)-coated polymeric scaffold infused with collagen (COL) that boosts the performance of transplanted alveolar bone-derived mesenchymal stem cells (aBMSCs). Electron microscopy revealed micron-sized (2.7 μm) polymeric fibers forming a porous (500 μm fiber strand spacing) composite scaffold with a uniform F/CaP coating homogeneously infiltrated with collagen. In vitro, our findings underscored the cytocompatibility of the collagen-infused F/CaP-coated composite scaffold, fostering a suitable environment for aBMSCs proliferation and differentiation. Cells within the F/CaP-coated constructs exhibited upregulated osteogenic gene activity, and the addition of collagen augmented the expression of critical bone-forming genes (i.e., Runx2 and OCN). After in vivo implantation, the scaffolds integrated well with the surrounding host tissue, supporting extensive blood vessel infiltration. Notably, the collagen-infused F/CaP-coated composite scaffolds showed an increased CD31-positive vessel growth compared to the non-coated counterparts. At 8 weeks, aBMSCs-laden F/CaP-Coated+COL composite scaffolds exhibited robust bone formation, creating connecting bony bridges in calvarial defects. Importantly, F/CaP-Coated+COL composite scaffolds displayed pronounced OCN expression, indicating enhanced osteogenic potential. Thus, the engineered F/CaP-coated polymeric scaffold laden with aBMSCs and infused with collagen has proven effective in supporting cell growth, vascularization, and rapid bone regeneration, suggesting potential for future clinical use.