Advanced biomaterials for skeletal tissue regeneration: Instructive and smart functions

The past half century has seen explosive growth in the use of medical implants. Orthopedic, cardiac, oral, maxillofacial and plastic surgeons are examples of medical specialists treating millions of patients each year by implanting devices varying from pace makers, artificial hip joints, breast and dental implants, to implantable hearing aids. All such medical implants make use of special materials, known as biomaterials, defined as ‘‘materials intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ, or function of the body’’ [D.F. Williams, The Williams Dictionnary of Biomaterials, Liverpool University Press, Liverpool, 1999]. While the priority for the first generation of biomaterials was inertness with living tissues, the field is shifting towards biologically active systems in order to improve their performance and to expand their use. Biomaterials can be combined as scaffolds with cells (i.e. tissue engineering), growth factors or genetic material in order to trigger tissue regeneration. In addition, recent reports have shown the possibility to design biomaterials that can activate cellular processes and tissue formation solely by their intrinsic physicochemical and three dimensional spatial properties. This article reviews the recent developments in the design of biomaterials that integrate our understanding of cellular and molecular mechanisms with materials science. After an overview of the physicochemical and biological processes occurring at the interface between the biomaterials and biological milieu, we will address the biological principles contributing to the design and engineering of advanced biomaterials for application towards recent therapeutic strategies for tissue regeneration. Finally, future directions for the design of advanced biomaterials will be discussed. # 2007 Elsevier B.V. All rights reserved.