Technological Assessment
Design, development, and benchmarking of a bioreactor integrated with 3D bioprinting
Tissue engineering approaches could be very promising in regenerating skeletal muscle, and bioprinting techniques have produced encouraging results, especially regarding 3D architecture. Tensile stimuli showed a fundamental role in regulating the behavior of muscle cells both in terms of 3D organization and protein expression. Despite this promising premise, the combination of 3D bioprinting and mechanical stimulation has been poorly investigated. The present work proposes the design, manufacturing, and benchmarking of a bioprinting-integrated mechanical platform conceived for mechanically stimulating a 3D muscle model directly printed into the bioreactor to foster the integration of printing and stimulation. The study consists of three main steps: 1) the design, fabrication, and mechanical characterization of stretchable supports suitable for bioprinting and long-term cell culture; 2) the design, assisted by computational tools, and the fabrication of the smart Petri dish containing the stimulation mechanism and of the final cyclic mechanical platform; 3) the in-vitro validation of the proposed platform in terms of transmission of the mechanical stimulation to the 3D construct and the biological effect of dynamic culture on 3D bioprinted muscle cells. The results highlighted excellent viability and demonstrated that the external stimulus influences the murine myoblasts behavior already after 7 days of culture. In conclusion, prototypes are now available of a mechanical platform that integrates 3D bioprinting and is capable of stimulating 3D biological constructs for applications in muscle tissue engineering.
Collaborations
- G. Ceccarelli, L. Benedetti, G. Cusella – Dept. Human Anatomy Unit, Dept. of Public Health, Exp. Medicine and Forensic, University of Pavia.
References
[1] G. Loi, F. Scocozza, L. Benedetti, F. Auricchio, S. Marconi, E. Delgrosso, G. Cusella, G. Ceccarelli, and M. Conti. “Design, development, and benchmarking of a bioreactor integrated with a 3D bioprinting: Application to skeletal muscle regeneration”. Bioprinting (2024) – doi: 10.1016/j.bprint.2024.e00352 – Open Access article under the CC BY license
Shape fidelity and sterility assessment of 3D printed polycaprolactone and hydroxyapatite scaffolds
Polycaprolactone (PCL) and hydroxyapatite (HA) composite are widely used in tissue engineering (TE). They are fitted to be processed with three-dimensional (3D) printing technique to create scaffolds with variable porosity. The current challenge is to guarantee the reliability and reproducibility of 3D printed scaffolds and to create sterile scaffolds which can be used for in vitro cell cultures. In this context it is important for successful cell culture to have a protocol in order to evaluate the sterility of the printed scaffolds.
This study, published in Journal of Polymer Research [1], proposed a systematic approach to sterilise 90%PCL-10%HA pellets using a 3D bioprinter before starting the printing process. We evaluated the printability of PCL-HA composite and the shape fidelity of scaffolds printed with and without sterilised pellets varying infill pattern, and the sterility of 3D printed scaffolds following the method established by the United States Pharmacopoeia. Finally, the thermal analyses supported by the Fourier Transform Infrared Spectroscopy were useful to verify the stability of the sterilisation process in the PCL solid state with and without HA.
The results show that the use of the 3D printer, according to the proposed protocol, allows to obtain sterile 3D PCL-HA scaffolds suitable for TE applications such as bone or cartilage repair.
Collaborations
- M. Sakaj, P. Riello – University Cà Foscari, University of Venice
- M. Scatto – Nadir S.r.l.
- L. Catenacci, M. Sorrenti – Department of Drug Sciences, University of Pavia
- C. Ferrari, L. Cansolino – Lab. Experimental Surgery, University of Pavia
References
[1] F. Scocozza, M. Sakaj, F. Auricchio, S. Marconi, P. Riello, C. Ferrari, L. Cansolino, L. Catenacci, M. Sorrenti, M. Scatto, M. Conti. “Shape fidelity and sterility assessment of 3D printed polycaprolactone and hydroxyapatite scaffolds”, Journal of Polymer Research (2021) – doi: 10.1007/s10965-021-02675-y – Open Access article under the CC BY license