Smart biomaterials with an inherent stimulating capacity that elicit specific behaviours in lieu of biological prompts would prove advantageous for regenerative medicine applications. Specific blends of the natural polymers cellulose and silk cast as films can drive the chondrogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) upon in vitro culture. However, the true potential of such biomaterials for cartilage tissue engineering can be realised upon its three-dimensional fabrication. In this work we employ an electrospinning technique to model the in vivo nanofibrous extracellular matrix (ECM). Cellulose and silk polymers at a mass ratio of 75:25 were regenerated using a trifluoroacetic acid and acetic acid cosolvent system. This natural polymer composite was directly electrospun for the first time, into nanofibers without post-spun treatment. The presence and size of fibre beading was influenced by environmental humidity. The regenerated composite retained the key chemical functionalities of its respective components. Biocompatibility of the natural polymer composite with hMSCs was demonstrated and its inherent capacity to direct chondrogenic stem cell differentiation, in the absence of stimulating growth factors, was confirmed. This physical chondrogenic stimulation was countered biochemically using fibroblast growth factor-2 (FGF-2), a growth factor used to enhance the proliferation of hMSCs. The newly fabricated scaffold provides the foundation for designing a robust, self-inductive, and cost-effective biomimetic biomaterial for cartilage tissue engineering.