Surface functionalization of 3D printed polymer scaffolds to augment stem cell response

Abstract

Three-dimensional (3D) printing by material extrusion is being widely explored to prepare patient-specific scaffolds from biodegradable polyesters such as poly(lactic acid) (PLA). Although they provide the desired mechanical support, PLA scaffolds lack bioactivity to promote bone regeneration. The aim of this work was to develop a surface engineering approach for enhancing the osteogenic activity of 3D printed PLA scaffolds. Macro-porous PLA scaffolds were prepared by material extrusion with 70.2% porosity. Polyethyleneimine was chemically conjugated to the alkali-treated PLA scaffolds followed by conjugation of citric acid. These polymer-grafted scaffolds were immersed in the simulated body fluid to yield scaffolds coated with calcium-deficient hydroxyapatite (PLA-HaP). Surface roughness and water wettability were enhanced after surface modification. PLA-HaP scaffolds exhibited a steady release of calcium ions in an aqueous medium for 10 days. The adhesion and proliferation of human mesenchymal stem cells (hMSCs) on PLA-HaP was ~50% higher than on PLA. Mineral deposition resulting from hMSC osteogenesis on PLA-HaP scaffolds was nearly twice that on PLA scaffolds. This was corroborated by the increase in alkaline phosphatase activity and expression of several osteogenic genes. Thus, this work presents a surface modification strategy to enhance the bioactivity of 3D printed scaffolds for bone tissue regeneration. Keywords: 3D printing, Tissue scaffold, Surface engineering, Hydroxyapatite, Stem cells