An appropriate surface chemical property is crucial in tissue engineering scaffolds, which promotes cell attachment and proliferation. A biomimetic composite scaffold with a polydopamine (PDA) coating layer on electrospun poly(lactic acid) (PLA)/cellulose nanofibrils (CNF) composite nanofiber was developed in this study. PLA/CNF composite nanofibers were fabricated and then coated via treatment with a dopamine solution. The PDA coating layer was successfully formed on the surface of the PLA/CNF composite nanofiber by using a simple, environment-friendly, and effective procedure. Results indicated that the addition of CNF into the PLA matrix can effectively improve the deposition rate of the PDA coating layer on the surface of the composite nanofiber during the initial stage of coating because of hydrogen bonding between the CNF and PDA molecular chains. The hydrophilicity and mechanical properties of the PLA/CNFPDA scaffold were higher than those of the PLA/CNF scaffold. In addition, the cell culture test showed that the adhesion, proliferation, and growth of human mesenchymal stem cells (hMSCs) cultured on the PLA/CNFPDA scaffold were significantly enhanced relative to those cultured on the PLA/CNF scaffold because of the introduction of the PDA coating. This finding suggested that surface biofunctionalization via the PDA coating layer could simply and effectively enhance cell biocompatibility for polymer-based scaffolds. (C) 2017 Elsevier Ltd. All rights reserved.