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1.
bioRxiv ; 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38712283

ABSTRACT

A successful pregnancy relies on the proper cellular, biochemical, and mechanical functions of the uterus. A comprehensive understanding of uterine mechanical properties during pregnancy is key to understanding different gynecological and obstetric disorders such as preterm birth, placenta accreta, leiomyoma, and endometriosis. This study sought to characterize the macro-scale equilibrium material behaviors of the human uterus in non-pregnancy and late pregnancy under both compressive and tensile loading. Fifty human uterine specimens from 16 patients (8 nonpregnant [NP] and 8 pregnant [PG]) were tested using spherical indentation and uniaxial tension coupled with digital image correlation (DIC). A three-level incremental load-hold protocol was applied to both tests. A microstructurally-inspired material model considering fiber architecture was applied to this dataset. Inverse finite element analysis (IFEA) was then performed to generate a single set of mechanical parameters to describe compressive and tensile behaviors. The freeze-thaw effect on uterine macro mechanical properties was also evaluated. PG tissue exhibits decreased overall stiffness and increased fiber network extensibility compared to NP uterine tissue. Under indentation, ground substance compressibility was similar between NP and PG uterine tissue. In tension, the fiber network of the PG uterus was found to be more extensible and dispersed than in nonpregnancy. Lastly, a single freeze-thaw cycle did not systematically alter the macro-scale material behavior of the human uterus.

3.
J Mech Behav Biomed Mater ; 154: 106509, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38518513

ABSTRACT

Gelatin methacryloyl (GelMA) hydrogels are widely used for a variety of tissue engineering applications. The properties of gelatin can affect the mechanical properties of gelatin gels; however, the role of gelatin properties such as bloom strength on GelMA hydrogels has not yet been explored. Bloom strength is a food industry standard for describing the quality of gelatin, where higher bloom strength is associated with higher gelatin molecular weight. Here, we evaluate the role of bloom strength on GelMA hydrogel mechanical properties. We determined that both bloom strength of gelatin and weight percent of GelMA influenced both stiffness and viscoelastic ratio; however, only bloom strength affected diffusivity, permeability, and pore size. With this library of GelMA hydrogels of varying properties, we then encapsulated Swan71 trophoblast spheroids in these hydrogel variants to assess how bloom strength affects trophoblast spheroid morphology. Overall, we observed a decreasing trend of spheroid area and Feret diameter as bloom strength increased. In identifying clear relationships between bloom strength, hydrogel mechanical properties, and trophoblast spheroid morphology, we demonstrate that bloom strength should considered when designing tissue engineered constructs.


Subject(s)
Gelatin , Tissue Scaffolds , Hydrogels , Tissue Engineering , Methacrylates
4.
J Mech Behav Biomed Mater ; 151: 106348, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38198930

ABSTRACT

The uterus has critical biomechanical functions in pregnancy and undergoes dramatic material growth and remodeling from implantation to parturition. The intrinsic material properties of the human uterus and how they evolve in pregnancy are poorly understood. To address this knowledge gap and assess the heterogeneity of these tissues, the time-dependent material properties of all human uterine layers were measured with nanoindentation. The endometrium-decidua layer was found to be the least stiff, most viscous, and least permeable layer of the human uterus in nonpregnant and third-trimester pregnant tissues. In pregnancy, the endometrium-decidua becomes stiffer and less viscous with no material property changes observed in the myometrium or perimetrium. Additionally, uterine material properties did not significantly differ between third-trimester pregnant tissues with and without placenta accreta. The foundational data generated by this study will facilitate the development of physiologically accurate models of the human uterus to investigate gynecologic and obstetric disorders.


Subject(s)
Decidua , Placenta , Pregnancy , Humans , Female , Uterus , Myometrium
5.
bioRxiv ; 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-38014304

ABSTRACT

Gelatin methacryloyl (GelMA) hydrogels are widely used for a variety of tissue engineering applications. The properties of gelatin can affect the mechanical properties of gelatin gels; however, the role of gelatin properties such as bloom strength on GelMA hydrogels has not yet been explored. Bloom strength is a food industry standard for describing the quality of gelatin, where higher bloom strength is associated with higher gelatin molecular weight. Here, we evaluate the role of bloom strength on GelMA hydrogel mechanical properties. We determined that both bloom strength of gelatin and weight percent of GelMA influenced both stiffness and viscoelastic ratio; however, only bloom strength affected diffusivity, permeability, and pore size. With this library of GelMA hydrogels of varying properties, we then encapsulated Swan71 trophoblast spheroids in these hydrogel variants to assess how bloom strength affects trophoblast spheroid morphology. Overall, we observed a decreasing trend of spheroid area and Feret diameter as bloom strength increased. In identifying clear relationships between bloom strength, hydrogel mechanical properties, and trophoblast spheroid morphology, we demonstrate that bloom strength should considered when designing tissue engineered constructs.

6.
APL Bioeng ; 7(4): 046103, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37854060

ABSTRACT

Atherosclerosis is a primary precursor of cardiovascular disease (CVD), the leading cause of death worldwide. While proprotein convertase subtilisin/kexin 9 (PCSK9) contributes to CVD by degrading low-density lipoprotein receptors (LDLR) and altering lipid metabolism, PCSK9 also influences vascular inflammation, further promoting atherosclerosis. Here, we utilized a vascular microphysiological system to test the effect of PCSK9 activation or repression on the initiation of atherosclerosis and to screen the efficacy of a small molecule PCSK9 inhibitor. We have generated PCSK9 over-expressed (P+) or repressed (P-) human induced pluripotent stem cells (iPSCs) and further differentiated them to smooth muscle cells (viSMCs) or endothelial cells (viECs). Tissue-engineered blood vessels (TEBVs) made from P+ viSMCs and viECs resulted in increased monocyte adhesion compared to the wild type (WT) or P- equivalents when treated with enzyme-modified LDL (eLDL) and TNF-α. We also found significant viEC dysfunction, such as increased secretion of VCAM-1, TNF-α, and IL-6, in P+ viECs treated with eLDL and TNF-α. A small molecule compound, NYX-1492, that was originally designed to block PCSK9 binding with the LDLR was tested in TEBVs to determine its effect on lowering PCSK9-induced inflammation. The compound reduced monocyte adhesion in P+ TEBVs with evidence of lowering secretion of VCAM-1 and TNF-α. These results suggest that PCSK9 inhibition may decrease vascular inflammation in addition to lowering plasma LDL levels, enhancing its anti-atherosclerotic effects, particularly in patients with elevated chronic inflammation.

7.
bioRxiv ; 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37609213

ABSTRACT

The uterus has critical biomechanical functions in pregnancy and undergoes dramatic material growth and remodeling from implantation to parturition. The intrinsic material properties of the human uterus and how they evolve in pregnancy are poorly understood. To address this knowledge gap and assess the heterogeneity of these tissues, the time-dependent material properties of all human uterine layers were measured with nanoindentation. The endometrium-decidua layer was found to be the least stiff, most viscous, and least permeable layer of the human uterus in nonpregnant and third-trimester pregnant tissues. In pregnancy, endometrium-decidua becomes stiffer and less viscous with no material property changes observed in the myometrium or perimetrium. Additionally, uterine material properties did not significantly differ between third-trimester pregnant tissues with and without placenta accreta. The foundational data generated by this study will facilitate the development of physiologically accurate models of the human uterus to investigate gynecologic and obstetric disorders.

8.
Biomed Mater ; 13(2): 025005, 2018 01 24.
Article in English | MEDLINE | ID: mdl-29033393

ABSTRACT

Tissue regeneration is a significantly improved alternative to tissue replacement by implants. It requires porous bioscaffolds for the restoration of natural tissue rather than relying on bio-inactive, often metallic implants. Recently, we developed technology for fabricating novel, nano-macroporous bioactive 'tailored amorphous multi-porous (TAMP)' hard tissue scaffolds using a 70 mol% SiO2-30 mol% CaO model composition. The TAMP silicate scaffolds, fabricated by a modified sol-gel process, have shown excellent biocompatibility via the rapid formation of hydroxyapatite in biological fluids as well as in early tests with bone forming cells. Here we report an in depth investigation of the response of MC3T3-E1 pre-osteoblast cells and bone marrow derived (BMD) osteoclasts to these TAMP scaffolds. Light and electron microscopic imaging, gene and protein expression, and enzyme activity analyses demonstrate that MC3T3-E1 pre-osteoblasts adhere, proliferate, colonize, and differentiate on and inside the bioactive TAMP scaffolds. Additionally, BMD precursor cells mature into active osteoclasts and remodel the scaffold, highlighting the exceptional qualities of this novel scaffold material for bone tissue regeneration.


Subject(s)
Biocompatible Materials , Bone Regeneration , Glass , Osteoblasts/cytology , Osteoclasts/cytology , Tissue Scaffolds/chemistry , 3T3 Cells , Animals , Bone and Bones/pathology , Cell Adhesion , Cell Differentiation , Cell Proliferation , Coculture Techniques , Durapatite/chemistry , Mice , Microscopy, Electron, Scanning , Models, Animal , Porosity , Rats , Rats, Sprague-Dawley , Silicates/chemistry , Silicon Dioxide , Tissue Engineering/methods
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