Sure, because of the plugin support it shouldn't get too complicated.

You can use strings instead of urls, for files. So you could do something like:

  loadFromS3(function (fileContent) {
    j = new Jotted($container, {
      files: [ type: 'css', content: fileContent ]
    })
  })

then create a plugin for it that saves the changes back to s3:

  j.done('change', function (err, params) {
    saveToS3(params.content)
  })

Here's some details about the plugin api: https://github.com/ghinda/jotted#plugin-api