The purpose of the present paper is to examine the socio-cultural foundations of technology-mediated collaborative learning. Toward that end, we discuss the role of artifacts in knowledge-creating inquiry, relying on the theoretical ideas of Carl Bereiter, Merlin Donald, Pierre Rabardel, Keith Sawyer and L. S. Vygotsky. We argue that epistemic mediation triggers expanded inquiry and plays a crucial role in knowledge creation; such mediation involves using CSCL technologies to create epistemic artifacts for crystallizing cognitive processes, re-mediating subsequent activity, and building an evolving body of knowledge. Productive integration of CSCL technologies as instruments of learning and instruction is a developmental process: it requires iterative efforts across extended periods of time. Going through such a process of instrumental genesis requires transforming a cognitive-cultural operating system of activity, thus "reformatting" the brain and the mind. Because of the required profound personal and social transformations, one sees that innovative knowledge-building practices emerge, socially, through extended expansive-learning cycles.