Background of Tissue Engineering Scaffolds

Tissue loss or defect, resulting from traumatic or nontraumatic destruction and failing to heal spontaneously, has been a major health problem that directly affects the life quality and length of human being in modern society. A large fraction of the nation’s health care costs are attributable to tissue loss or defect, and approximately 8 million surgical procedures are performed annually in the United States to treat these disorders. Over 10 million new cases of various tissue defects are annually reported. It is pressed for the need for the development of functional therapeutic strategies. Current treatment of organ failure or tissue loss involves tissue grafts or surgical reconstruction or mechanical devices such as kidney dialyzers [1]. These therapies have revolutionized medical practice but have disadvantages. The source of autografts is extremely limited and this method ineluctably brings additional pains to the patients. They have also been treated with the help of tissue or organ procured from the donors. But these allografts usually causes immunologic rejection and the spread of disease. And the source of appropriate donor organs is also limited. More than 70,000 patients are currently awaiting using tissue graft, but fewer than 11,000 tissue graft are available annually [2]. Furthermore, the mismatch of supply and demand has been wider and wider. In these circumstances, some additional functional devices are used to replace some functions of the injured tissues or organs. However, these implants have a limited service life. Therefore, a revolutionary strategy has long expected to achieve permanent tissue repair rather than transient tissue replacement [3-5]. Fortunately, tissue engineering has been developed as a promising method to obtain the goal [6-9].

To date, it has been shown that nearly every tissue and organ in the human body has been attempted to engineer in vitro. Work has been proceeding worldwide for many years in the soft tissue engineering and hard tissue engineering, such as cartilage [10], bone [11], hair [12], nerves [13], tendons [14], ligaments [15], fascia, skin [16], fibrous tissues, blood vessels [17] and even heart muscle [18] and valves [19]. The highest levels of success have been achieved in the areas of skin, bladder, airway and bone, where tissue-engineered constructs have been successfully used in patients [5, 20]. Generally, tissue engineering seeks to fabricate functional implants, which can induce tissue regeneration [21]. The implants are artificial synthesized materials, called scaffolds or the complexes of cells and scaffolds. A major advantage of this approach is that the desired tissues can be regenerated to precisely repair the tissue defect or loss. Therefore, tissue engineering can hopefully overcome the shortages of tissue grafts, surgical reconstructions and mechanical devices for tissue repair, and be only one approach that can meet the current huge demand quantity of tissue repair.

At present, tissue engineering has been developed into two types. One is in vitro tissue engineering, which is that a functionalized complex of cells and scaffold, cultured together under appropriate conditions in vitro that lead to desired new tissue formation, is implanted to repair tissue defect or loss [5, 22]. The other is in vivo tissue engineering, which is that only a high-performanced scaffold is implanted, and that the ample tissue regeneration needed cells can be successfully recruited by the functionalized scaffolds in vivo, which are further induced into the desired

tissues.

One obvious advantage of in vitro tissue engineering is that the cells can be freely selected and cultured on the scaffolds according to the tissue regeneration requirements without the restriction of the complicated biological environment. And, their behaviors, such as attachment, proliferation, differentiation and biomineralization, etc., can be controlled by the techniques in vitro. Furthermore, the prepared complexes of cells and scaffolds can be timely tracked, observed, analyzed and studied, and it is possible to further improve their functions by additional techniques in vitro if necessary. Normally, three key factors should be considered to achieve the satisfactory tissue repair efficency for the in vitro tissue engineering: (i) the accurate selection of the appropriate cells, contributing to the formation of the desired tissue and normally harvested from the patients or donors, (ii) the successful preparation of the effective scaffolds, serving as a mimic of extracellular matrix, which can not only offer enough mechanical support for the embedded cells, but also create a three-dimensional superior growth environment for the cells to contribute to the desired tissue formation, and (iii) reasonable control of the interactions between the cells and the scaffolds to achieve functionalized cell-scaffold complexes that can direct the course of the desired tissue regeneration in vivo by control of various interactions with components of living systems, which finally results in tissue repair. Of course, the disadvantages of in vitro tissue engineering are also obvious. Because the cell-scaffold complexes are developed in vitro, it is still doubtable that they can fully accomplish the expected mission after implanted into human body, where they have to undergo a variety of unprecedented impacts in vivo, such as human normal body fluid environment, metabolism, blood circulation, biomechanical effects, interactions together with extremely abundant types of proteins and enzymes, etc. For example, it has been proved that biomechanical stimulation is an important factor for cell functions, and can significantly affect the structures and functions of new formed tissues.

In vivo tissue engineering can overcome these disadvantages of in vitro tissue engineering because only scaffolds are implanted. However, it has a higher requirement for the performances of scaffolds than in vivo tissue engineering. Above all, no matter which type of tissue engineering, scaffolds lie at their hearts and play crucial role for their success. Therefore, scaffolds have been regarded as a hot and fashionable research area in this field [23-26].

 
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