TY - JOUR

T1 - Enabling Technologies for Obtaining Desired Stiffness Gradients in GelMA Hydrogels Constructs

AU - Sauty, Bastien

AU - Santesarti, Gianluca

AU - Fleischhammer, Tabea

AU - Lindner, Patrick

AU - Lavrentieva, Antonina

AU - Pepelanova, Iliyana

AU - Marino, Michele

N1 - Funding Information: M.M. acknowledges the Italian Ministry of Education, University and Research (MIUR) for funding in the “Programma per Giovani Ricercatori ‐ anno 2017 Rita Levi Montalcini”. A.L. and I.P. acknowledge the support by the German Research Foundation (DFG Project 398007461 488 3D Dual‐Gradient Systems for Functional Cell Screening) and by the SMART BIOTECS initiative, financially supported by the Ministry of Science and Culture (MWK) of Lower Saxony, Germany. The authors also express their gratitude to Dr. Janina Bahnemann and her group for providing them with the 3D printed micromixer.

PY - 2022/1/22

Y1 - 2022/1/22

N2 - This work presents enabling technologies for the optimization of the manufacturing of GelMA-based hydrogels constructs with desired stiffness gradients. The manufacturing technique combines dynamic mixing for gradient generation and a passive micromixer for efficient hydrogel blending. A digital replica of the fabrication process is developed, integrating theoretical and computational models, as well as experimental data, in order to predict and control the stiffness profile obtained within the constructs. The workflow for the development of the in silico framework, based on rigorous verification, validation, and uncertainty quantification steps, is presented. The validation of the digital replica is based on reference settings of process variables, which result in constructs with an exponential stiffness profile. The developed in silico model has been employed for optimizing process variables in order to obtain a linear stiffness profile in the extruded construct without the need of expensive and time-consuming trial-and-error procedures. The developed digital replica is now a powerful tool for the creation of hydrogel gradient constructs for tissue engineering applications or for the screening of optimal 3D cell culture conditions.

AB - This work presents enabling technologies for the optimization of the manufacturing of GelMA-based hydrogels constructs with desired stiffness gradients. The manufacturing technique combines dynamic mixing for gradient generation and a passive micromixer for efficient hydrogel blending. A digital replica of the fabrication process is developed, integrating theoretical and computational models, as well as experimental data, in order to predict and control the stiffness profile obtained within the constructs. The workflow for the development of the in silico framework, based on rigorous verification, validation, and uncertainty quantification steps, is presented. The validation of the digital replica is based on reference settings of process variables, which result in constructs with an exponential stiffness profile. The developed in silico model has been employed for optimizing process variables in order to obtain a linear stiffness profile in the extruded construct without the need of expensive and time-consuming trial-and-error procedures. The developed digital replica is now a powerful tool for the creation of hydrogel gradient constructs for tissue engineering applications or for the screening of optimal 3D cell culture conditions.

UR - http://www.scopus.com/inward/record.url?scp=85121438374&partnerID=8YFLogxK

U2 - 10.1002/macp.202100326

DO - 10.1002/macp.202100326

M3 - Article

AN - SCOPUS:85121438374

VL - 223

JO - Macromolecular Chemistry and Physics

JF - Macromolecular Chemistry and Physics

SN - 1022-1352

IS - 2

M1 - 2100326

ER -