The prevalent challenge facing tissue engineering today is the lack of adequate vascularization to support the growth, function, and viability of tissue substitutes that require blood vessel supply. Researchers rely on the increasing knowledge of angiogenic and vasculogenic processes to stimulate vascular network formation within three-dimensional tissue constructs. These processes are mainly endothelial cell-regulated, although in the context of tissue engineering, specific interactions with scaffold materials, growth factors and other cell types may require in vitro vascularization schemes to be altered accordingly. To better mimic the complete in vivo environment, increasing attention is given to the integration of co-cultures and mechanical conditioning in bioreactors. Such approaches show great promise for the enhancement of the functionality and clinical applicability of tissue engineering constructs. This paper reviews some scaffold materials used in tissue engineering and the effect of their properties on the vascularization process. Also, it specifically addresses the pivotal role of biomaterials vascularization in tissue engineering applications, along with the effect of angiogenic factors and adhesive molecules on angiogenesis. Assays and markers of angiogenesis are also outlined. One section highlights the need for bioreactor cultures and mechanical conditioning in controlling endothelial cell responses. Finally, we conclude with a brief section on the effects of oxygen concentration and hypoxia over microvessel formation.

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The aim of this study was to develop an in vitro cell culture system allowing studying the effect of separation distance between monolayers of rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVEC) co-cultured in fibrin over INS-1 cell insulin secretion. For this purpose, a three-dimensional (3D) cell culture chamber was designed, built using micro-fabrication techniques and validated. The co-culture was successfully carried out and the effect on INS-1 cell insulin secretion was investigated. After 48 and 72 h, INS-1 cells co-cultured with HUVEC separated by a distance of 100 µm revealed enhanced insulin secretion compared to INS-1 cells cultured alone or co-cultured with HUVEC monolayers separated by a distance of 200 µm. These results illustrate the importance of the separation distance between two cell niches for cell culture design and the possibility to further enhance the endocrine function of beta cells when this factor is considered.