**1. Introduction**

*Unmet need.* It is beyond dispute that human population is ageing. For the first time in history, people age 65 and over will outnumber children under age 5. This trend is emerging around the globe, and will bring several challenges for health technologies. For instance, in a few decades, the loss of health and life worldwide will be greater from chronic diseases than from infectious diseases and accidents [4].

The report made by the National Institute of Health and the National Institute of Aging (NIH/ NIA) underscores the unmet needs lying ahead for regenerative medicine. Chronic diseases, in opposition to infectious diseases, are mainly treated by regenerative approaches, instead of immunization and antibiotics.

Actually, many of those challenges are already present in our daily living: malformations [9,14], accidents [16], chronic infections [9,15], and end-organ failure [17] (usually occurs during the final stages of degenerative and other diseases), may, in some cases, only be treated by organ replacement. In fact, end-organ failure alone already affects millions of Americans. More specifically, nearly six million Americans suffer from heart failure with approximately 550,000 new cases diagnosed annually, 530,000 Americans suffer from end-stage renal disease and nearly 25 million Americans suffer from chronic obstructive pulmonary disease with an estimated 12 million new annual diagnoses [5]. As already stated, for many of those patients, organ transplantation is their only treatment option. Currently, organ transplantation is considered the best option for some patients and achieves up to 98,5% of patient 1-year survival rates [18]. Unfortunately, though, current organ shortage/recovering engenders waiting lines of up to three or more years [5]. During 2008, for instance, the number of heart transplantations

© 2013 Carvalho et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

decreased 2,67%, even though waiting lines increased during the same year. Such decrease occurred mainly due to a reduction in number of recovered organs [18].

It is clear that alternatives to organ transplantation need to be developed as soon as possible. That`s where tissue engineering comes into picture.

*Tissue engineering.* Tissue engineering refers to an "interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function" [3]. The term was first coined by Dr. Fung, from California University, which suggested this name during the National Science Foundation Meeting, in 1987 [2]. The first official definition dates to 1988, though, when Skalak and Fox published it after the "Tissue engineering Meeting" held in Lake Tahoe, USA during that year [1].

In 1993, Langer and Vacanti described three strategies for the creation of new tissue in vitro [3].


Currently, tissue engineering focuses mainly of associating cells with supports (also called biomaterials or scaffolds), in order to: i. promote cell attachment and restrict their distribution in the tissue, ii. direct cell distribution and differentiation, iii. sustain large tissue losses while new tissue is formed, and ultimately, to iv. lead to new tissue formation.

Since its early days, tissue engineering has significantly evolved in each of its pillars – Cells, signaling molecules and scaffolds. This evolution covered both conceptual aspects - as evidenced above – as well as practical aspects, mainly reflected in the achievements of the field (for more information, go to conclusion section). Unfortunately, even though cells and signaling molecules platforms have evolved during the past decades, leading to major field evolution, the degree of success of tissue engineering methods is still highly dependent on the properties of the scaffold. Therefore, this study focuses on the main Achille`s Hill of tissue engineering: production of scaffolds for biological applications.

**Figure 1.** Tissue engineering strategies. Based on [59]. Tissue engineering may be performed by several different ap‐ proaches, as proposed by Langer and Vancanti. In order to obtain tissue regeneration, cells, scaffolds and signaling molecules may be introduced into the body alone or in association. Currently, the association of all three elements, composing bioactive constructs, is proposed to be the best option for tissue engineering.

In the present chapter, we present the current status of tissue engineering. First, we present a comprehensive picture of classical tissue engineering approaches, as well as an analytic view of its main achievements and limitations. Secondly, we present innovative and para‐ digm breaking strategies for successful tissue engineering, accompanied by the history and rationale behind each of them. Finally, we analyze the next steps of tissue engineering trans‐ lation into the clinic.
