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Three-dimensional decellularized tumor extracellular matrices with different stiffness as bioengineered tumor scaffolds.

ABSTRACT: In the three-dimensional (3D) tumor microenvironment, matrix stiffness is associated with the regulation of tumor cells behaviors. In vitro tumor models with appropriate matrix stiffness are urgently desired. Herein, we prepare 3D decellularized extracellular matrix (DECM) scaffolds with different stiffness to mimic the microenvironment of human breast tumor tissue, especially the matrix stiffness, components and structure of ECM. Furthermore, the effects of matrix stiffness on the drug resistance of human breast cancer cells are explored with these developed scaffolds as case studies. Our results confirm that DECM scaffolds with diverse stiffness can be generated by tumor cells with different lysyl oxidase (LOX) expression levels, while the barely intact structure and major components of the ECM are maintained without cells. This versatile 3D tumor model with suitable stiffness can be used as a bioengineered tumor scaffold to investigate the role of the microenvironment in tumor progression and to screen drugs prior to clinical use to a certain extent.

SUBMITTER: Lv Y

PROVIDER: S-EPMC7897907 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Three-dimensional decellularized tumor extracellular matrices with different stiffness as bioengineered tumor scaffolds.

Lv Yonggang Y Wang Hongjun H Li Gui G Zhao Boyuan B

Bioactive materials 20210215 9

In the three-dimensional (3D) tumor microenvironment, matrix stiffness is associated with the regulation of tumor cells behaviors. <i>In vitro</i> tumor models with appropriate matrix stiffness are urgently desired. Herein, we prepare 3D decellularized extracellular matrix (DECM) scaffolds with different stiffness to mimic the microenvironment of human breast tumor tissue, especially the matrix stiffness, components and structure of ECM. Furthermore, the effects of matrix stiffness on the drug r ...[more]

PMID: 33665508

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Project description:The precise mechanisms that lead to orthopedic implant failure are not well understood; it is believed that the micromechanical environment at the bone-implant interface regulates structural stability of an implant. In this work, we seek to understand how the 3D mechanical environment of an implant affects bone formation during early osteointegration. We employed two-photon lithography (TPL) direct laser writing to fabricate 3-dimensional rigid polymer scaffolds with tetrakaidecahedral periodic geometry, herewith referred to as nanolattices, whose strut dimensions were on the same order as osteoblasts' focal adhesions (?2?m) and pore sizes on the order of cell size, ?10?m. Some of these nanolattices were subsequently coated with thin conformal layers of Ti or W, and a final outer layer of 18nm-thick TiO2 was deposited on all samples to ensure biocompatibility. Nanomechanical experiments on each type of nanolattice revealed the range of stiffnesses of 0.7-100MPa. Osteoblast-like cells (SAOS-2) were seeded on each nanolattice, and their mechanosensitve response was explored by tracking mineral secretions and intracellular f-actin and vinculin concentrations after 2, 8 and 12days of cell culture in mineralization media. Experiments revealed that the most compliant nanolattices had ?20% more intracellular f-actin and ?40% more Ca and P secreted onto them than the stiffer nanolattices, where such cellular response was virtually indistinguishable. We constructed a simple phenomenological model that appears to capture the observed relation between scaffold stiffness and f-actin concentration. This model predicts a range of optimal scaffold stiffnesses for maximum f-actin concentration, which appears to be directly correlated with osteoblast-driven mineral deposition. This work suggests that three-dimensional scaffolds with titania-coated surfaces may provide an optimal microenvironment for cell growth when their stiffness is similar to that of cartilage (?0.5-3MPa). These findings help provide a greater understanding of osteoblast mechanosensitivity and may have profound implications in developing more effective and safer bone prostheses. STATEMENT OF SIGNIFICANCE:Creating prostheses that lead to optimal bone remodeling has been a challenge for more than two decades because of a lack of thorough knowledge of cell behavior in three-dimensional (3D) environments. Literature has shown that 2D substrate stiffness plays a significant role in determining cell behavior, however, limitations in fabrication techniques and difficulties in characterizing cell-scaffold interactions have limited our understanding of how 3D scaffolds' stiffness affects cell response. The present study shows that scaffold structural stiffness affects osteoblasts cellular response. Specifically this work shows that the cells grown on the most compliant nanolattices with a stiffness of 0.7MPa expressed ?20% higher concentration of intracellular f-actin and secreted ?40% more Ca and P compared with all other nanolattices. This suggests that bone scaffolds with a stiffness close to that of cartilage may serve as optimal 3D scaffolds for new synthetic bone graft materials.

Dataset Information

Three-dimensional decellularized tumor extracellular matrices with different stiffness as bioengineered tumor scaffolds.

Publications

Three-dimensional decellularized tumor extracellular matrices with different stiffness as bioengineered tumor scaffolds.

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