Surface engineering of 3D-printed polylactic acid scaffolds with polydopamine and 4-methoxycinnamic acid-chitosan nanoparticles for bone regeneration.

Bone remodeling, a continuous process of resorption and formation, is essential for maintaining skeletal integrity and mineral balance. However, in cases of critical bone defects where the natural bone remodeling capacity is insufficient, medical intervention is necessary. Traditional bone grafts have limitations such as donor site morbidity and availability, driving the search for bioengineered scaffold alternatives. The choice of biomaterial is crucial in scaffold design, as it provides a substrate that supports cell adhesion, proliferation, and differentiation. Poly-lactic acid (PLA) is known for its biocompatibility and biodegradability, but its hydrophobicity hinders cell attachment and tissue regeneration. To enhance PLA's bioactivity, we fabricated 3D-printed PLA scaffolds using fused deposition modelling. They were then surface-treated with NaOH to increase their reactivity, followed by polydopamine (PDA) and 4-methoxycinnamic acid (MCA)-loaded chitosan nanoparticle (nCS) coatings though polyelectrolyte complexation. Even though MCA, a polyphenolic, is known for its therapeutic properties, its osteogenic potential is not yet known. MCA treatment in mouse mesenchymal stem cells (mMSCs) promoted increased levels of Runx2 mRNA, a key bone transcription factor. Due to MCA's hydrophobic nature, nCS were used as carriers. The PLA/PDA/nCS-MCA scaffolds exhibited exceptional compressive strength and bioactivity. Biocompatibility tests confirmed that these scaffolds were non-cytotoxic to mMSCs. Overall, this study highlights the osteogenic potential of MCA and demonstrates the improved biocompatibility, bioactivity, wettability, and cell adhesion properties of the PDA/nCS-MCA-coated PLA scaffolds, positioning it as a promising material for bone tissue regeneration.