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ICE Krakow

ICE Krakow

ul. Marii Konopnickiej 17 30-302 Kraków


Campillo, Noelia (REGEMAT 3D S.L.)


The biomedical sector is experiencing a technological transformation in its attempt to solve current and next future global health issues. The scarcity of organ donors in a growing elderly population accentuates the need to generate new strategies based on the use of cutting-edge technologies for regenerative medicine.
In recent years, the emergence of 3D bioprinting has allowed great advances in tissue engineering, making feasible the automatized and controlled ex vivo generation of bioartificial substitutes with a certain degree of complexity. The controlled application of biomimetic biochemical, physical and mechanical stimuli of a given tissue within custom-designed bioreactors for each bioprinting application is critical to promote the maturation of the 3D construct towards a functional tissue with clinical applications. All these stimuli are well-acknowledged to be critical players in determining cellular fate and functions during tissue formation, homeostasis and disease. However, there are so far no bioreactors available in the market for tissue engineering. Technical complexity and economic costs are main factors that have limited their development by research institutions and companies.
REGEMAT 3D has developed a novel bioreactor that mimics the anatomy and physiology of the human knee (BMAP Knee) and promotes cartilage regenerative processes under a controlled microenvironment. The bioreactor maintains the temperature, the O2 and CO2 concentrations of the cell culture within the physiological range and can apply typical movements of the knee (flexo-extension, compression and rotation) in patient-specific knee joint models obtained by 3D bioprinting.
In a pilot study, reconstruction of the human knee joint was performed through 3D printing from MRI data of a patient with osteochondral lesions in lateral and medial condyles of the femur. Polylactic acid was employed for the printing of femur and tibia while menisci and osteochondral lesions where printed with polycaprolactone to provide them with more flexibility. 3D Cell culture was performed within osteochondral lesions using a bioink composed by human adipose tissue-derived mesenchymal stem cells and a hydrogel of collagen type 1. The application of compressive mechanical loads (0.3 Hz, 4h/day, total of 21 days) under physiological conditions of temperature, CO2 y O2 concentrations promoted the activation of genes encoding the SOX9 transcription factor, collagen type 2 (COL2A1) protein and aggrecan (ACAN) proteoglycan, which are the most abundant components of the cartilage extracellular matrix. These results suggest the activation of chondrogenic differentiation the differentiation of mesenchymal cells in the osteochondral lesions in response to mechanical stimuli. In addition, cell viability and proliferation measurements demonstrated the bioreactor’s capacity to maintain the scaffolds under appropriate physiological parameters and sterile conditions in the long term, thus validating its use for tissue engineering purposes.

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