Design requirements and additive manufacturing of bioreactors for tissue engineering and mechanobiology

Bioreactors are enabling technologies in tissue engineering and mechanobiology research fields because they provide controlled environments that sustain cell viability, improve mass transport, and deliver tissue-specific biochemical and biophysical stimuli. Their development remains a multidisciplinary challenge, requiring the integration of biological, engineering, manufacturing, and operational requirements. In this context, additive manufacturing (AM) has emerged as a design-enabling technology that supports rapid prototyping, geometric customization, and the in-house fabrication of application-specific bioreactor components. This chapter provides a comprehensive overview of the engineering principles underlying the design and fabrication of bioreactors for tissue engineering and mechanobiology investigations, with particular emphasis on the opportunities and challenges related to AM. It first discusses the biological and engineering requirements that govern device design, with particular attention to biocompatibility, sterility, and control of culture conditions. It then examines three AM technologies widely adopted for bioreactor fabrication: fused deposition modeling (FDM), stereolithography (SLA), and selective laser sintering (SLS). For each technology, the working principle and available materials are described alongside advantages and limitations, and their complementary roles are highlighted through representative applications. Particular attention is also given to deformable components and to the effects of post-processing and sterilization on final device performance. Finally, practical guidelines for technology selection are presented together with current challenges and future perspectives, including hybrid manufacturing, integrated sensing, automation, and closed-loop control strategies, which may support the development of even more physiologically relevant bioreactor platforms.