Completely new materials can only be created by the Pixologic team. Modifications of existing materials (which can create almost anything imaginable) can only be done with the Material palette modifiers.
When you load a material, it overwrites whatever material is currently selected in the Material palette. If that material is live anywhere in the scene (meaning that it’s in use on the canvas, and has not been baked), then the scene will update with the new material. This allows many interesting effects, and also can be used to enhance your workflow. For example, you can build your scene using the various Fast Shader materials, which render on the fly very easily, even at large canvas sizes. When you are done laying the scene out, you can then load new materials to replace the stand-ins.
To replace a material that is in use in the canvas without affecting the canvas, you have two choices:
A) Bake the scene. This will, of course, fix all shadows in place so be sure that you have your lighting and stuff set up first.
B) Save the in-use material. Then select a different unused material and load the saved material back into it. You can now adjust this cloned material any way that you’d like without affecting the original (or any parts of the canvas that use it). This is actually a very effective way to layer materials on top of each other without getting those “jaggies” that happen when very different materials intersect. You can make small changes to the cloned material and then paint it over the first material without any edges showing. Southern uses this technique to create different materials for lips, cheeks, forehead, etc. Some of his images have 5 different materials for the face, alone, with only slight changes between them.
If you wish to save a texture with modified materials, there are two things that you must do. First, save the custom materials. Second, save the Tool with the texture wrapped onto it, and click Yes when asked if you would like to save the texture with the Tool. Later, when you load the tool, the texture will automatically be loaded with it and the material info will still be embedded. As you suspect, the material customizations will be lost. BUT it’s very easy to get them back. Click on the large thumbnail in the Material palette and drag onto the canvas. It will become a picker. Let go of the mouse when the picker is over top of one of your tool’s material zones – that material will automatically be selected. Then load the previously saved material to replace it. In this way, you don’t ever have to remember what slots you used; you only have to remember what you named each custom material for the object.