Cell interactions in bone tissue engineering

Abstract

Bone fractures, where the innate regenerative bone response is compromised, represent between 4 and 8 hundred thousands of the total fracture cases, just in the United States. Bone tissue engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell-to-cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented.

Fig 1

Positive (+) and negative (–) effects of cell-to-cell interactions between different cell types relevant in bone biology. Cell differentiation, function and proliferation were the reviewed parameters.

Fig 2

Distribution and organization of hDMECs and hOBs in co-culture on SPCL fibre mesh scaffolds after 35 days of culture. In order to distinguish between the two cell populations, samples were stained for PECAM-1(CD31; green fluorescence, endothelial-specific) and nuclei (blue fluorescence, both hOBs and hDMECs). (This picture is a kind gift of Marina I. Santos.)

Fig 3

Collagen IV immunohistochemical staining of thin-section of hDMECs and hOBs in co-culture on SPCL fibre meshes after 35 days of culture. Nuclei were counterstained with Mayer’s haematoxylin. ‘*’ identifies the scaffold material. (This figure is a kind gift of Marina I. Santos.)