Investigating How All-Trans Retinoic Acid Polycaprolactone (atRA-PCL) Microparticles Alter the Material Properties of 3D Printed Fibrin Constructs.

The 3D printing of human tissue constructs requires carefully designed bioinks to support the growth and function of cells. Here it is shown that an additional parameter is how drug-releasing microparticles affect the material properties of the scaffold. A microfluidic platform is used to create all-trans retinoic acid (atRA) polycaprolactone (PCL) microparticles with a high encapsulation efficiency (85.9 ± 5.0%), and incorporate them into fibrin constructs to investigate their effect on the material properties. An encapsulation that is around 25-35% higher than the current state of the art batch methods is achieved. It is also found that the drug loading concentration affects the microparticle size, which can be controlled using the microfluidic platform. It is shown that the release of atRA is slower in fibrin constructs than in buffer, and that the presence of atRA in the microparticles modulates both the degradation and the rheological properties of the constructs. Finally, it is shown that the fibrin material exhibits a stronger solid-like state in the presence of atRA-PCL microparticles. These findings establish a basis for understanding the interplay between drug-releasing microparticles and scaffold materials, paving the way for bioinks that achieve tailored degradation and mechanical properties, together with sustained drug delivery for tissue engineering applications.