Illustrative workflow for high-throughput microarray studies in
cellular applications (representations not to scale). First, microarray
fabrication can be done through automated liquid dispensing systems
(contact printing with a solid or quilled pin, or inkjet printing).
Second, high-throughput is carried out for (1) material analysis technologies
(e.g., time-of-flight mass spectrometry (ToF SIMS), WCA, X-ray photoelectron
spectroscopy (XPS), atomic force microscopy (AFM)), and (2) biological
performance. Third, biological and structural data are correlated,
and used to generate structure–activity relationship models.
The material library can be further mined through combinatorial microarrays
of the highest performing biomaterials, and computational models can
be generated from the available data sets. After extensive mining
of the microarray-generated data, scale-up studies take the best-performing
polymers onto bigger platforms, such as multiwell tissue culture plates,
robot-assisted automated cell culture platforms using RoboFlasks,
or 3D culture by generating microparticles from the hit polymers and
using them in Bioreactor-based strategies. In-depth cell-based studies
(e.g., proliferation assessment, transcriptional analysis, and specific
cell marker immunostaining) can then be performed in parallel to investigate
the long-term effect of “hit” polymers on cellular behavior.
Ultimately, preclinical studies on animals, followed by clinical trials
are undertaken to ensure the biomaterial’s safety and effectiveness
in biomedical applications.