Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances - PubMed (original) (raw)

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Cell microenvironment engineering and monitoring for tissue engineering and regenerative medicine: the recent advances

Julien Barthes et al. Biomed Res Int. 2014.

Abstract

In tissue engineering and regenerative medicine, the conditions in the immediate vicinity of the cells have a direct effect on cells' behaviour and subsequently on clinical outcomes. Physical, chemical, and biological control of cell microenvironment are of crucial importance for the ability to direct and control cell behaviour in 3-dimensional tissue engineering scaffolds spatially and temporally. In this review, we will focus on the different aspects of cell microenvironment such as surface micro-, nanotopography, extracellular matrix composition and distribution, controlled release of soluble factors, and mechanical stress/strain conditions and how these aspects and their interactions can be used to achieve a higher degree of control over cellular activities. The effect of these parameters on the cellular behaviour within tissue engineering context is discussed and how these parameters are used to develop engineered tissues is elaborated. Also, recent techniques developed for the monitoring of the cell microenvironment in vitro and in vivo are reviewed, together with recent tissue engineering applications where the control of cell microenvironment has been exploited. Cell microenvironment engineering and monitoring are crucial parts of tissue engineering efforts and systems which utilize different components of the cell microenvironment simultaneously can provide more functional engineered tissues in the near future.

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Figures

Figure 1

Figure 1

The effect of microlevel mechanical confinement on the division of HeLa cells. (a) and (b) show the macroscopic structure of the microfluidic system and the cross-section of PDMS posts. By the application of pressure on the posts, cells can be confined within the area between the posts (the distance between the posts is 40 _μ_m) (c). The confinement caused significant changes in the behavior of the cells during mitosis, such as delays in mitosis, and led to daughter cells of different sizes and multidaughter cells following mitosis. Reproduced from [4].

Figure 2

Figure 2

Bone formation via endochondral pathway. An in vitro formed artificial cartilage successfully forms a bone containing bone marrow within 12 weeks. The in vitro grown tissue is a cartilaginous one as evidenced by the extensive safranin O staining; over time, the cartilaginous tissue has been gradually replaced by bone tissue, as can be seen by the extensive Masson's Trichrome staining. Micro-CT images also showed the development of a bone like structure within 12 weeks. Reproduced from [8].

Figure 3

Figure 3

Manipulating the cell microenvironment in 3D via encapsulation within hydrogels. Encapsulation of prostate cancer cells within PEG hydrogels resulted in more pronounced cell-cell contacts as evidenced by E-cadherin staining (a) and also formation of a necrotic core within the cell aggregates as shown by pimonidazole staining (b). All scale bars are 75 _μ_m for (a) and 100 _μ_m for (b). Reproduced from [9].

Figure 4

Figure 4

The main types of soluble factors that have distinct effects on the cellular behaviour at both single cell and tissue level. Controlled delivery of such factors and their regulated presence in cell microenvironment is an indispensable tool in tissue engineering research. Reproduced from [10].

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