Plug and play: combining materials and technologies to improve bone regenerative strategies.

Despite recent advances in the development of biomaterials intended to replace natural bone grafts for the regeneration of large, clinically relevant defects, most synthetic solutions that are currently applied in the clinic are still inferior to natural bone grafts with regard to regenerative potential and are limited to non-weight-bearing applications. From a materials science perspective, we always face the conundrum of the preservation of bioactivity of calcium phosphate ceramics in spite of better mechanical and handling properties and processability of polymers. Composites have long been investigated as a method to marry these critical properties for the successful regeneration of bone and, indeed, have shown a significant improvement when used in combination with cells or growth factors. However, when looking at this approach from a clinical and regulatory perspective, the use of cells or biologicals prolongs the path of new treatments from the bench to the bedside. Applying 'smart' synthetic materials alone poses the fascinating challenge of instructing tissue regeneration in situ, thereby tremendously facilitating clinical translation. In the journey to make this possible, and with the aim of adding up the advantages of different biomaterials, combinations of fabrication technologies arise as a new strategy for generating instructive three-dimensional (3D) constructs for bone regeneration. Here we provide a review of recent technologies and approaches to create such constructs and give our perspective on how combinations of technologies and materials can help in obtaining more functional bone regeneration.