In adult organisms the regenerative capacity of certain organs or tissues can be limited, resulting in an important clinical challenge for physicians and scientists [1-3].
Regeneration involves the capacity for renewal or recomposition of tissues, organs or even organisms, after considerable physical injury or damage, resulting from pathologies, tumors, congenital diseases or traumas, for example. As a consequence of tissue regeneration, both the composition and the tissue properties are restored, and the newly formed tissue is highly similar to the original tissue. The regenerative capacity is directly related to the presence of stem cells or progenitor cells, which are capable of proliferation and differentiation [4,5]. Tissues that maintain a high proliferative capacity, such as the hematopoietic system, have regenerative capacity even in adult organisms [6].
Cell proliferation occurs in repair processes in general, accompanied by intense production of extracellular matrix, with large amounts of collagen, resulting in the formation of fibrous tissue to occupy the injured area. Although there is lesion filling, both the composition and the tissue properties are different from the original tissue, and the tissue organization pattern is not restored, leading to an altered performance of its functions [2]. Skin healing processes with the presence of scars are examples of tissue repair [3].
Besides the natural processes of regeneration and repair, it is possible, through medical intervention, to fill lesions with natural or synthetic materials, aiming at the recovery of the compromised area, and conferring certain properties to the tissue, avoiding, for example, exacerbation of the initial lesion or the evolution of degenerative processes [1,7].
The three approaches can be used in tissue engineering, targeting regenerative medicine, as they allow the recovery of compromised areas in different degrees. However, the primary objective is regeneration, recomposition of the original tissue and resumption of the biomechanical and molecular properties, with the normal performance of their functions [1,7-8].
Tissue regeneration involves cell recruitment, growth, proliferation and differentiation, with the latter representing a crucial stage for the success of regeneration, avoiding the formation of fibrous tissue characteristic of the repair [9-12]. Tissues with greater regenerative capacity, such as the skin and liver, intrinsically present cells able to migrate to occupy the affected region, and the same cells maintain the proliferative capacity, enabling occupation of the lesion [3]. In other tissues the regenerative capacity is even more impaired. In the cartilage, for example, the cells remain embedded in the extracellular matrix, and the absence of blood vessels inhibits the presence of other types of component cell in the tissue; even the cell migration and proliferation processes are compromised. In general, regeneration and repair processes do not occur naturally in these cases, requiring surgical intervention to stimulate the subchondral bone marrow, thus enabling the presence of cells capable of tissue repair in the compromised area [13]. Other scientific techniques and methodologies seek alternatives to enable the processes both of repair and of tissue regeneration [9-12,14-16].
Anyhow the final stage of the abovementioned processes, cell differentiation, is critical. An understanding of the mechanisms that lead to the differentiation process in adult organisms allows the proposition of improvements in existing technologies and of alternatives geared towards the optimization of guided tissue regeneration processes, in regenerative medicine.
