To me it seems that the greatest obstacle to space colonization would be maintenance and production of materials and technology needed to sustain and expand the colony. Seems like the last step for truly becoming self sustaining. You'd need extremely small scale factories that can build everything needed for a modern civilization. I wonder what that would take. What the smallest amount of shipments and time would be.…
And that pesky radiation slowly killing you.
Of course it would help to develop better treatments for radiation exposure.