(M-489) Parameters for 3D-printing a multi-compositional PLGA microsphere-based scaffold: temporally adaptive bio-printing

Introduction:: Microspheres, synthesized from diverse natural or synthetic polymers, are readily being utilized in biomedical tissue engineering to improve the healing of various tissues. Their ability to entrap growth factors, medications, natural bio-molecules required for tissue formation like bone or cartilage and even stem cells are making microspheres invaluable for future clinical therapies. Whilst microsphere-supplemented scaffolds exist, a fully derived and pure microsphere-based scaffold with an optimized architecture has been difficult to create due to physical and flow-based issues that prevent consistent deposition of microspheres and the ability to maintain the shape of a 3D-printed structure.

Our aim was to determine and establish a new 3D-printing methodology, which not only would allow us to generate large microsphere-based scaffolds but also permit the creation of multi-gradient matrices into which cells, growth factors and therapeutics, entrapped in microspheres, could be directly deposited during the printing process.


Materials and Methods:: Poly(lactic co-glycolic acid) (PLGA) microspheres were fabricated on a Buchi Encapsulator B-390 and mixed with a small amount of a carboxymethyl cellulose solution as a temporary lubricant/carrier for printing. Utilizing the extrusion printing process, multilayered scaffolds were generated by 3D-printing with these bioinks on an Envisiontec Bioplotter Manufacturing Series. Printing parameters were established for the bioinks and adapted for different layers of the scaffolds to allow for appropriate solidification of the scaffold layers.



Results, Conclusions, and Discussions:: Our method of "temporally adaptive printing" addresses issues with scaffold shape fidelity typically resulting due to ink viscosity and gravity. By including carefully timed breaks, miniscule drying steps together with adjustments to extrusion parameters over time, we generated an evenly layered microsphere-based scaffold in excess of 10 mm in height that contains internal geometric configurations required to support cellular invasion/migration.

By using this process we were able to generate the first 3D-printed entirely microsphere-based scaffold. This process allows us to create scaffolds with load bearing capability that can release encapsulated biomolecules in an extremely localized and timed fashion to study cell responses to the delivered signals in order to generate multiple tissues addressing scaffolds, e.g. for osteochondral defects.




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