TY - JOUR

T1 - Experimental characterization and computational modeling of hydrogel cross-linking for bioprinting applications

AU - Hajikhani, Aidin

AU - Scocozza, Franca

AU - Conti, Michele

AU - Marino, Michele

AU - Auricchio, Ferdinando

AU - Wriggers, Peter

N1 - Funding information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: A.H. and M.M. acknowledge that this work has been carried out within the framework of the SMART BIOTECS alliance between the Technical University of Braunschweig and the Leibniz University of Hannover. This initiative is financially supported by the Ministry of Science and Culture (MWK) of Lower Saxony, Germany. Moreover, F.A., M.C., and F.S. acknowledge the 3D@UniPV Project.

PY - 2019/10

Y1 - 2019/10

N2 - Alginate-based hydrogels are extensively used to create bioinks for bioprinting, due to their biocompatibility, low toxicity, low costs, and slight gelling. Modeling of bioprinting process can boost experimental design reducing trial-and-error tests. To this aim, the cross-linking kinetics for the chemical gelation of sodium alginate hydrogels via calcium chloride diffusion is analyzed. Experimental measurements on the absorbed volume of calcium chloride in the hydrogel are obtained at different times. Moreover, a reaction-diffusion model is developed, accounting for the dependence of diffusive properties on the gelation degree. The coupled chemical system is solved using finite element discretizations which include the inhomogeneous evolution of hydrogel state in time and space. Experimental results are fitted within the proposed modeling framework, which is thereby calibrated and validated. Moreover, the importance of accounting for cross-linking-dependent diffusive properties is highlighted, showing that, if a constant diffusivity property is employed, the model does not properly capture the experimental evidence. Since the analyzed mechanisms highly affect the evolution of the front of the solidified gel in the final bioprinted structure, the present study is a step towards the development of reliable computational tools for the in silico optimization of protocols and post-printing treatments for bioprinting applications.

AB - Alginate-based hydrogels are extensively used to create bioinks for bioprinting, due to their biocompatibility, low toxicity, low costs, and slight gelling. Modeling of bioprinting process can boost experimental design reducing trial-and-error tests. To this aim, the cross-linking kinetics for the chemical gelation of sodium alginate hydrogels via calcium chloride diffusion is analyzed. Experimental measurements on the absorbed volume of calcium chloride in the hydrogel are obtained at different times. Moreover, a reaction-diffusion model is developed, accounting for the dependence of diffusive properties on the gelation degree. The coupled chemical system is solved using finite element discretizations which include the inhomogeneous evolution of hydrogel state in time and space. Experimental results are fitted within the proposed modeling framework, which is thereby calibrated and validated. Moreover, the importance of accounting for cross-linking-dependent diffusive properties is highlighted, showing that, if a constant diffusivity property is employed, the model does not properly capture the experimental evidence. Since the analyzed mechanisms highly affect the evolution of the front of the solidified gel in the final bioprinted structure, the present study is a step towards the development of reliable computational tools for the in silico optimization of protocols and post-printing treatments for bioprinting applications.

KW - bioprinting

KW - chemical cross-linking

KW - diffusive properties

KW - gelation

KW - Sodium alginate

UR - http://www.scopus.com/inward/record.url?scp=85068616044&partnerID=8YFLogxK

U2 - 10.1177/0391398819856024

DO - 10.1177/0391398819856024

M3 - Article

C2 - 31267806

AN - SCOPUS:85068616044

VL - 42

SP - 548

EP - 557

JO - International Journal of Artificial Organs

JF - International Journal of Artificial Organs

SN - 0391-3988

IS - 10

ER -