Reimagining bioprinters: real-time monitoring for quality control of bioprinted constructs and future vision.

Abstract

The use of bioprinters as depositional tools for bioinks and cells has expanded greatly over the past two decades. Bioprinting combines hydrogels with cells to produce customized constructs for personalized medicine. However, several challenges hinder the clinical use of these constructs. Quality control metrics for bioprinting involve the assessment of critical quality attributes (CQAs) at every stage of production. Currently, bioprinted constructs are manually assessed using destructive methods that occur post-production, requiring the creation of multiple products per patient. Reproducing printed constructs is difficult due to time-sensitive bioink properties that require lengthy optimization processes to print with accuracy. In addition, the collection, processing, and testing of cell bioactivity for each printed construct greatly increases production costs. To address these challenges, non-destructive, real-time monitoring can be integrated into the bioprinting process. The goal of this review paper is to reimagine the function of a bioprinter from a simple tool of production to one capable of evaluating constructs in real-time. This review features recent advances in the field for real-time monitoring with a focus on time-sensitive bioink properties, print accuracy, and cell health. Automated assessment and quantification of time-sensitive bioink qualities such as mixing, pH, temperature, and viscosity will enhance construct quality by enabling the rapid optimization of printing parameters. Meanwhile, real-time monitoring of cell health through concentration, viability, and type serves as an indicator for bioactivity. Construct accuracy and reproducibility are also improved through the identification, prediction, and correction of defects during printing. Incorporating real-time monitoring into the bioprinting process using closed-loop feedback would improve the reproducibility, quality, and translation of constructs into the clinic. .