What do you think it would take to make a self-sustaining Mars colony?
The first thing it would take is sufficient reason to create such a colony.
Once that epiphany hits enough of the right people, it will take a fundamental change in human nature to successfully follow through with the decades (or centuries) of work needed. I'm thinking it would take a city of several thousands on Mars before it could be considered "self-sufficient".
I don't personally foresee that ever happening. After all, there are many sparsely inhabited regions right here on Earth we don't feel compelled to live in, and so I don't really expect condition #1 to be met.