Development of a bioreactor culture chamber to support maturation of 3D biohybrid bone repair constructs

Perfusion bioreactors are engineered systems designed to stimulate cell proliferation on three dimensional scaffolds by recreating physiologically relevant microenvironmental conditions. The present research focuses on an advanced perfusion bioreactor development project promoted by Osteobionix PS S.L., aimed at creating a dedicated system for the dynamic three dimensional culture of mesenchymal stem cells (MSCs) on patient-specific porous titanium scaffolds for bone regeneration applications. The primary focus was the design and optimization of a custom-made culture chamber specifically tailored to a patient-specific supraorbital cranial scaffold. The culture chamber geometry was designed using Autodesk Fusion 360. The final prototype was printed with a biocompatible resin BioMed Flex 80A using a stereolithography (SLA) 3D printer. This material was selected due to its mechanical properties and certified biocompatibility. The perfusion bioreactor design integrates a Hei-FLOW Platinum peristaltic pump to generate a controlled and reproducible medium flow, enhancing mass transport and providing physiologically relevant shear stress stimulation. Literature evidence supports the effectiveness of perfusion culture in improving MSC distribution, metabolic activity, viability and osteogenic differentiation compared to static culture systems. The system was conceived to be compatible with sensors for real-time monitoring of dissolved oxygen, pH, temperature and glucose concentration. By combining customized chamber design, controlled mechanical microenvironment and prospective multi-stimulus integration, the proposed approach contributes to more homogeneous cell colonization, reduction of stagnation regions, optimization of perfusion flow distribution and accurate control of local shear stress applied to MSCs, ultimately supporting improved construct maturation for personalized bone regeneration.