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

Arwa Daghrery, Renan Dal-Fabbro, Jinping Xu, Darnell Kaigler, Mylène de Ruijter, Debby Gawlitta, Jos Malda, Marco C. Bottino*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article number214222
JournalBiomaterials advances
Volume170
DOIs
Publication statusPublished - May 2025

Keywords

  • Bone
  • Collagen
  • Engineering
  • Melt electrowriting
  • Regeneration
  • Stem cells
  • Transplantation

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