The Evolution and Application of Regenerative Engineering
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The Evolution and Application of Regenerative Engineering Roshan James, Ph.D.1,2,3 and Cato T. Laurencin, M.D., Ph.D.1,2,3,4,5,* 1
Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut 06030, USA 2 Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Connecticut 06030, USA 3 Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut 06030, USA 4 Connecticut Institute for Clinical and Translational Science, Farmington, Connecticut 06030, USA 5 Department of Chemical, Materials and Biomolecular Engineering, University of Connecticut, Storrs, Connecticut 06269, USA ABSTRACT Current treatment options for tissue loss or organ failure include organ/tissue transplantation of autografts/allografts, delivery of bioactive agents, and utilization of synthetic replacements composed of metals, polymers, and ceramics. However each strategy suffers from a number of limitations. The early attempts to overcome these drawbacks led to the emergence of tissue engineering that provided viable tissue substitutes using a combination of biomaterials, cells, and factors. This approach was ideally suited to repair damaged tissues; however the substitution and regeneration of large tissue volumes and multi-level tissues such as complex organ systems require more than optimal combinations of biomaterials and biologics. ‘Regenerative Engineering’ is aimed at creating large and complex tissue systems incorporating advances in material science, stem cell technology and developmental biology. We believe that recent breakthrough technologies in advanced materials science and nanotechnology allow us to recapitulate native tissues. The novel designer polymers incorporate bioactivity and physical features specific to a regeneration application. Overall, engineered materials and scaffolds afford selective control of cell sensitivity, and precise control of temporal and spatial stimulatory cues. We aim to build multi-level systems such as organs through location-specific topographies and physico-chemical cues incorporated into a continuous phase using a combination of classical top-down tissue engineering approach with bottom-up strategies used in regenerative biology. Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration show extremely limited endogenous regenerative capacity. The development of material and structural platforms to modulate stem cell behavior to enhance regeneration is an area of great interest. In this manuscript we cover some examples of material development, and incorporation of topographical and cytokine cues to modulate the differentiation of hard and soft musculoskeletal tissues such as bone, ligament and tendon. INTRODUCTION Tissue engineering, advanced material science and stem cell science have been the frontiers of biomedical research over the past 25 years, aiming particularly to regenerate and rest
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