Citric acid modification of PLLA nano-fibrous scaffolds to enhance cellular adhesion, proliferation and osteogenic differentiation

Citric acid (CA) was used in a thermally induced phase separation (TIPS) process to improve the surface hydrophilicity and cell affinity of PLLA nano-fibrous scaffolds. The evolution of architecture, structure and physicochemical properties of the scaffold after modification has been investigated. Cell viability, adhesion, proliferation and osteogenic differentiation were characterized to evaluate the cytocompatibility and biological properties of PLLA nano-fibrous scaffolds. Citric acid interacted with PLLA through hydrogen bond association and the introduction of strong polar groups (-COOH) on the PLLA surface improved its hydrophilicity with the contact angle decreasing to a suitable range for cell adhesion and spreading. The cell exhibited extensive spreading on the CA modified PLLA scaffolds with many cellular protrusions interacting with nanofibers. Furthermore, such a modification significantly increased the cell proliferation rate, enhanced the alkaline phosphatase (ALP) activity and bone-related gene expression (ALP, OCN, COL I and Runx2) of mBMSCs along with cell development. The results demonstrate a promising modification method to promote applications of PLLA-based scaffolds.