Smart bioreactor for advanced osteochondral tissue models
Osteochondral defects affecting both cartilage and underlying bone are difficult to repair because the two tissues have distinct structures, mechanical properties and biological environments. As degenerative diseases such as osteoarthritis become an increasing burden, conventional treatments remain limited. When it comes to tissue engineering, production and investigation of functional replacements faces a major challenge in recreating the complex physical conditions that guide tissue development inside the joint.
Recreating the osteochondral environment
With the support of the Marie Skłodowska-Curie Actions(opens in new window) programme, the SYNERGIES project addressed this gap by developing an advanced research platform designed to reproduce key structural and biophysical features of the native osteochondral tissue environment. To achieve this, the researchers combined 3D-printed bilayer scaffolds(opens in new window) with controlled, tissue-specific physical stimulation delivered by a purpose-built biomimetic bioreactor. Rather than treating osteochondral tissue as a uniform structure, the platform separates the bone and cartilage regions into two compartments. This allows each compartment to receive appropriate differentiation media and physical cues. “SYNERGIES moved beyond simplified static models and investigated how developing osteochondral tissues respond to more physiologically relevant conditions,” explains research fellow Joao Silva.
Optimising stimulation with modelling and AI
The platform was supported by multiphysics modelling to characterise several parameters including fluid flow, shear stress, pressure, deformation and electromagnetic fields(opens in new window) within the culture chamber and constructs. This helped researchers determine how stimulation parameters develop within the bioreactor for investigating how they influence the cells. Machine learning was integrated into the control architecture to combine modelling outputs with experimental data and guide the optimisation of operating conditions. The resulting platform was validated through in vitro cell culture experiments, which supported the progressive optimisation of osteochondral tissue engineering protocols. The modular bioreactor was fabricated using biocompatible, autoclavable materials with an easy-to-use architecture designed to facilitate future compliance with good laboratory and manufacturing practices requirements.
Building better models for disease and drug research
Beyond tissue regeneration, the SYNERGIES platform offers a route towards more physiologically relevant human 3D models for studying osteochondral biology and disease. By combining human cells, biomimetic scaffolds and controlled physical stimulation, researchers can establish healthy and diseased tissue models – including models of osteoarthritis – under reproducible conditions. Moreover, the platform could help in drug discovery by identifying ineffective or potentially harmful candidates earlier in development, potentially reducing the number of compounds that need to progress to animal studies. “The value of these models extends beyond tissue regeneration. By reproducing the interaction between bone and cartilage in a controlled, native-like environment, we can investigate disease mechanisms and evaluate potential treatments under conditions that more closely resemble those found in the human joint,” emphasises SYNERGIES project supervisor Diana Massai. The project’s long-term goal is to translate the platform into a robust and scalable technology. Further work will be needed to validate long-term performance and test patient-derived cells, while standardising culture protocols and addressing safety, regulatory and cost considerations. Intellectual property protection and collaboration with clinical and industrial partners will also be important.
