I'm thinking that it might be a good idea to start by having a chat with your book binder.
The folks that I've used for the book binding have both a machine which binds the pages by their edges, and a machine which sews groups of pages together in the conventional way.
If you were to go with edge binding, the page numbering is a lot simpler, but the strength of the paper becomes an issue. I don't believe that thicker paper is a handicap with this method. However, the longevity of the binding is considered to be shorter than with conventional binding.
With the conventional method, I think that you are correct in thinking that the thickness of the pages could be an issue, but unfortunately I don't have any personal experience with this kind of binding. I'm not sure of the maximum paper size for the R2880, but I suspect that it prints A3+, which would let you go this route.