BIOENGINEERING,FOOD,AND NATURAL PRODUCTS Advances in Biomaterials,Drug Delivery,and Bionanotechnology Dept.of Chemical Engineering.Massa obert f .Cambridge,MA.02139 Nicholas A.Peppas maceutics,The University of Texas at Austin engineer al,materials and approaches used in drug and protein delivery systems,materials used Introduction the rapidly changing f onger is the treatment o engin (m gress in these fields over anre coupled coey th e coupled clos Polymeric Materials as Biomaterials The development of biomaterials has been an evolving p clinical us were no d clopment of ing wa the last 3 contained in therapeutic or diagnostic systems that are in sed for artificial heart y are use n man ral role in extra complications Dialys Dacron-b ed va grafts can only be used if their diam biomat found in about 8,000 dif it 6 mm.Otherw tions.Althougl inter ns (Peppas and Langer, physical. ng this artiele should he d to R.Lange properties to biomaterials.Materials have either been syn- 990 December 2003 Vol.49.No.12 AIChE Journal BIOENGINEERING, FOOD, AND NATURAL PRODUCTS Advances in Biomaterials, Drug Delivery, and Bionanotechnology Robert Langer Dept. of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139 Nicholas A. Peppas Depts. of Chemical and Biomedical Engineering, and Div. of Pharmaceutics, The University of Texas at Austin, Austin, TX, 78712 Biomaterials are widely used in numerous medical applications. Chemical engineer￾ing has played a central role in this research and de®elopment. Polymers as biomateri￾als, materials and approaches used in drug and protein deli®ery systems, materials used as scaffolds in tissue engineering, and nanotechnology and microfabrication techniques applied to biomaterials are re®iewed. Introduction In the rapidly changing scientific world, contributions of scientists and engineers are leading to major new solutions of significant medical problems. No longer is the treatment of diabetes, osteoporosis, asthma, cardiac problems, cancer, and other diseases based only on conventional pharmaceutical formulations. Biology and medicine are beginning to reduce the problems of disease to problems of molecular science, and are creating new opportunities for treating and curing disease. Such advances are coupled closely with advances in biomaterials and are leading to a variety of approaches for relieving suffering and prolonging life. Of particular interest is the central position that materials Ž . especially polymers, ceramics and metals have taken in the development of novel treatments over the last 30 years. Bio￾materials are generally substances other than food or drugs contained in therapeutic or diagnostic systems that are in contact with tissue or biological fluids. They are used in many biomedical and pharmaceutical preparations, they play a cen￾tral role in extracorporeal devices, from contact lenses to kid￾ney dialyzers, and are essential components of implants, from vascular grafts to cardiac pacemakers. There are many cur￾rent biomaterials applications, found in about 8,000 different kinds of medical devices, 2,500 separate diagnostic products, and 40,000 different pharmaceutical preparations. Although biomaterials already contribute greatly to the improvement of health, the need exists for better polymer, ceramic, and metal systems and improved methods of characterizing them Ž . Peppas and Langer, 1994 . Correspondence concerning this article should be addressed to R. Langer In this article we discuss recent advances in the fields of: Ž. Ž . i polymers as biomaterials; ii materials in drug and protein delivery; iii materials for tissue engineering; and iv materi- Ž . Ž. als used in nanotechnology and microfabrication of medical devices. We analyze scientific progress in these fields over the last ten years, and we stress the impact of chemical engi￾neering thinking on developments in this field. Polymeric Materials as Biomaterials The development of biomaterials has been an evolving pro￾cess. Many biomaterials in clinical use were not originally de￾signed as such, but were off-the-shelf materials that clinicians found useful in solving a problem. Thus, dialysis tubing was originally made of cellulose acetate, a commodity plastic. The polymers initially used in vascular grafts, such as Dacron, were derived from textiles. The materials used for artificial hearts were originally based on commercial-grade polyurethanes. These materials allowed serious medical problems to be ad￾dressed. Yet, they also introduced complications. Dialysis tubing may activate platelets and the complement system. Dacron-based vascular grafts can only be used if their diame￾ter exceeds about 6 mm. Otherwise, occlusion can occur be￾cause of biological reactions at the blood-material and tissue-material interfaces. Blood-materials interactions can also lead to clot formation in an artificial heart, with the sub￾sequent possibility of stroke and other complications Peppas Ž and Langer, 1994 .. In the last few years, novel synthetic techniques have been used to impart desirable chemical, physical, and biological properties to biomaterials. Materials have either been syn- 2990 December 2003 Vol. 49, No. 12 AIChE Journal