Review: bioreactor design towards generation of relevant engineered tissues: focus on clinical translation

Abstract

In tissue engineering and regenerative medicine, studies that utilize 3D scaffolds for generating voluminous tissues are mostly confined in the realm of in vitro research and preclinical animal model testing. Bioreactors offer an excellent platform to grow and develop 3D tissues by providing conditions that mimic their native microenvironment. Aligning the bioreactor development process with a focus on patient care will aid in the faster translation of the bioreactor technology to clinics. In this review, we discuss the various factors involved in the design of clinically relevant bioreactors in relation to their respective applications. We explore the functional relevance of tissue grafts generated by bioreactors that have been designed to provide physiologically relevant mechanical cues on the growing tissue. The review discusses the recent trends in non-invasive sensing of the bioreactor culture conditions. It provides an insight to the current technological advancements that enable in situ, non-invasive, qualitative and quantitative evaluation of the tissue grafts grown in a bioreactor system. We summarize the emerging trends in commercial bioreactor design followed by a short discussion on the aspects that hamper the 'push' of bioreactor systems into the commercial market as well as 'pull' factors for stakeholders to embrace and adopt widespread utility of bioreactors in the clinical setting. Copyright © 2017 John Wiley & Sons, Ltd.

Four-Dimensional Bioprinting for Regenerative Medicine: Mechanisms to Induce Shape Variation and Potential Applications

“…13 Additionally, the fluid-flow regime, the environmental control (oxygen levels, pH, temperature, and metabolite control), the stimulation (culture medium, growth factors, and stimulus), and their influence on cellular behaviour are the most important parameters to control for each type of tissue. 42 The development of new bioreactors with embedded sensory elements and imaging could guarantee real-time control of the process and enable automated feedback. Accordingly, the authors envision that systems able to withstand different types of stimuli (e.g., mechanic-like rotating, confined, or sliding compression/tension) to simulate native tissue loads and impacts, or to induce directional orientation (e.g., electric/ magnetic), are the future of bioreactors.…”

Biomimetic system design for engineering biofidelic 3-D respiratory tissuesin vitro

“…More recently, increased understanding of the critical role of mechanical stimuli in modulating cellular functions has prompted development of in vitro culture devices that aim to replicate tissue and organ-specific biomechanical conditions [12][13][14]. Such systems may employ perfusion or direct mechanical actuation to stimulate a 3-D construct [12,[15][16][17][18][19], where the method of delivering stimulus and system design are determined by model and application specific requirements [20,21]. Several strategies for respiratory tissue engineering have been described, including decellularized ECM scaffolds [22][23][24], air-liquid interface well inserts [25][26][27] and PDMS microfluidic chips with integrated 2-D membranes [27][28][29].…”

A Perfusion Bioreactor System for Cell Seeding and Oxygen-Controlled Cultivation of Three-Dimensional Cell Cultures

“…2–5 The application of bioreactor systems allows for the improvement of tissue quality by coping with limitations of static cultivation and by providing proper cultivation conditions for instance to mimic an in vivo -like environment. 3 , 6 …”

“… 22–24 To maintain OCs at an optimal level during a cultivation process, not only real-time sensing but also an automated feedback mechanism is needed. 3 , 6 , 25 Nonetheless, many bioreactor systems lack integrated oxygen sensor technology 9–11 or use sensor signals solely to observe present culture conditions. 26–28 …”

“…Besides integrated measurement instrumentation, the parallelization of bioreactors improves the functionality of a system significantly; not only because parallel experimental setups are much more time effective than subsequent approaches but also because the conduction of several parallel experiments allows for the investigation of several parameters in one run. 3 , 6 , 29 Most bioreactor systems include the option of multiplexing. 9 , 10 , 30–32 However, to display variations in an oxygen-controlled environment, bioreactors within a system have to be operating independently.…”