Hollow Fiber Bioreactor Technology for Tissue Engineering Applications

Hollow fiber bioreactors are the focus of scientific research aiming to mimic physiological vascular networks and engineer organs and tissues in vitro. The reason for this lies in the interesting features of this bioreactor type, including excellent mass transport properties. Indeed, hollow fiber bioreactors allow limitations to be overcome in nutrient transport by diffusion, which is often an obstacle to engineer sizable constructs in vitro. This work reviews the existing literature relevant to hollow fiber bioreactors in organ and tissue engineering applications. To this purpose, we first classify the hollow fiber bioreactors into 2 categories: cylindrical and rectangular. For each category, we summarize their main applications both at the tissue and at the organ level, focusing on experimental models and computational studies as predictive tools for designing innovative, dynamic culture systems. Finally, we discuss future perspectives on hollow fiber bioreactors as in vitro models for tissue and organ engineering applications. </jats:p

Development of a compliant and cytocompatible micro-fibrous polyethylene terephthalate vascular scaffold

Bioengineering approaches have been intensively applied to create small diameter vascular grafts using artificial materials. However, a fully successful, high performing and anti-thrombogenic structure has not been achieved yet. In this study, we have designed and fabricated a novel non-woven fibrous vascular graft with biomechanical properties closely resembling those of native vessels. Vascular cell growth, preservation of cell phenotype, retention of vasoactive properties, as well as the effect of gelatin coating on the cellular interaction with the scaffolds under static and shear stress conditions were investigated. The non-woven fibrous scaffolds were made from melt blown polyethylene terephthalate fiber webs stacked by means of a consolidation technique. The scaffold variables were fiber diameter distribution and the number of consolidated web stacks. SEM analysis confirmed various fiber diameter and pore size ranges corresponding to the different conditions. The scaffolds showed burst pressure values of ~1500 mmHg and compliance (8.4 6 \ub1 1.0 7 10\u207b\ub2% mmHg\u207b\ub9) very similar to those of native arteries (~8 7 10\u207b\ub2% mmHg\u207b\ub9). The structure with the smallest fiber diameter range (1\u20135 \ub5m) and pore size range (1\u201320 \ub5m) was the most suitable for the growth of human brain endothelial cells and aortic smooth muscle cells. The cells maintained their specific cell phenotype, expressed collagen and elastin and produced cAMP in response to \u3b1-calcitonin gene-related peptide. However, under shear stress conditions (0.9 dyne cm\u207b\ub2), only 30% of the cells were retained in both uncoated and gelatincoated scaffolds indicating the need for improving the cell retention capacity of these structures, which is our future research direction. This study indicates that the biomechanical and biocompatible properties of this novel vascular scaffold are promising for the development of a vascular graft with similar characteristics to those of native vessels.Peer reviewed: YesNRC publication: Ye

A multiphase model for chemically- and mechanically- induced cell differentiation in a hollow fibre membrane bioreactor: minimising growth factor consumption

We present a simplified two-dimensional model of fluid flow, solute transport, and cell distribution in a hollow fibre membrane bioreactor. We consider two cell populations, one undifferentiated and one differentiated, with differentiation stimulated either by growth factor alone, or by both growth factor and fluid shear stress. Two experimental configurations are considered, a 3-layer model in which the cells are seeded in a scaffold throughout the extracapillary space (ECS), and a 4-layer model in which the cell-scaffold construct occupies a layer surrounding the outside of the hollow fibre, only partially filling the ECS. Above this is a region of free-flowing fluid, referred to as the upper fluid layer. Following previous models by the authors (Pearson et al. in Math Med Biol, 2013, Biomech Model Mechanbiol 1-16, 2014a, we employ porous mixture theory to model the dynamics of, and interactions between, the cells, scaffold, and fluid in the cell-scaffold construct. We use this model to determine operating conditions (experiment end time, growth factor inlet concentration, and inlet fluid fluxes) which result in a required percentage of differentiated cells, as well as maximising the differentiated cell yield and minimising the consumption of expensive growth factor