New therapies to treat bone diseases and repair bone defects are urgently needed. Bone repair usually takes two forms: the use of autografts or alloplastic (synthetic) material replacements. Both approaches have serious limitations. Bone grafting requires a second surgical site, with associated discomfort, morbidity, and risk to the patient, and is restricted by the limited amount of bone. Most synthetic biomaterials were developed originally for other engineering applications, and often do not integrate well with host tissue and can result in infection, foreign-body reactions, and extrusion or loss of the implanted material. Their outcome is time-limited and unpredictable. An alternative that has attracted widespread attention in recent years is the engineering of new bone to replace the damaged or diseased tissue. A critical component of this tissue engineering approach is the development of porous 3D structures —scaffolds— that will provide cell support and guide bone formation. Numerous porous materials have been investigated, but despite substantial progress in the field, it has not been possible to develop synthetic structures able to fully harness the bone’s capability to regenerate and remodel itself.

There are multiple physical and biological requirements that a synthetic bone scaffold should address. It must supply a porous matrix with interconnected porosity and tailored surface chemistry for cell growth and penetration, enable the transport of nutrients and metabolic waste, and yet possess sufficient strength and stiffness to withstand physiological loads during integration and healing. It should be resorbed or remodeled in a programmed way, producing only metabolically acceptable substances with controlled osteogenic activity. In addition, its mechanical properties should match those of the host tissues, and the strength and stability of the material-tissue interface should be maintained while the material is resorbed or remodeled. Furthermore, because the ideal scaffold does not exist, each application requires a specific design with well-defined material properties. However, we still lack the basic design criteria needed to select materials and design architectures.

Our approach to this complex task is to combine new materials development with radically novel design philosophies, producing bioactive scaffolds that are intended to be partially or completely resorbed and replaced by bone from the host —a sequence resembling bone remodeling. Our vision is to design, synthesize, and characterize (structurally, biologically, and mechanically) a new series of hierarchical/hybrid scaffolds. The unique properties of these scaffolds derive from architectures controlled over a wide range of length scales from nano to macro dimensions. The main (but not sole) inspiration for these structures is biological, as Nature is generally able to defeat the "law of mixtures" by devising complex hierarchical structures uniting weak constituents into strong and tough hybrid materials. A key component of our work is the development of processing techniques flexible enough to produce materials with a wide spectrum of solubilities (bioresorption rates) and mechanical properties matching those of calcified tissues: low density, low stiffness, and high strength. These techniques will also have the capability of generating structures with different gradients in solubility and porosity to further control integration of the materials.