New Insight into Natural Extracellular Matrix: Genipin Cross-Linked Adipose-Derived Stem Cell Extracellular Matrix Gel for Tissue Engineering

Abstract

<jats:p>The cell-derived extracellular matrix (ECM) is associated with a lower risk of pathogen transfer, and it possesses an ideal niche with growth factors and complex fibrillar proteins for cell attachment and growth. However, the cell-derived ECM is found to have poor biomechanical properties, and processing of cell-derived ECM into gels is scarcely studied. The gel provides platforms for three-dimensional cell culture, as well as injectable biomaterials, which could be delivered via a minimally invasive procedure. Thus, in this study, an adipose-derived stem cell (ADSC)-derived ECM gel was developed and cross-linked by genipin to address the aforementioned issue. The genipin cross-linked ADSC ECM gel was fabricated via several steps, including rabbit ADSC culture, cell sheets, decellularization, freeze–thawing, enzymatic digestion, neutralization of pH, and cross-linking. The physicochemical characteristics and cytocompatibility of the gel were evaluated. The results demonstrated that the genipin cross-linking could significantly enhance the mechanical properties of the ADSC ECM gel. Furthermore, the ADSC ECM was found to contain collagen, fibronectin, biglycan, and transforming growth factor (TGF)-β1, which could substantially maintain ADSC, skin, and ligament fibroblast cell proliferation. This cell-derived natural material could be suitable for future regenerative medicine and tissue engineering application.</jats:p>

Collagen Bioinks for Bioprinting: A Systematic Review of Hydrogel Properties, Bioprinting Parameters, Protocols, and Bioprinted Structure Characteristics

“…Thus, both of them are considered as a viscoelastic solid [ 173 ]. Similar results were obtained in the study of Nyambat et al, where collagen hydrogels crosslinked by genipin showed increased stiffness and complex viscosity, while the cell morphology and viability of incorporated adipose-derived stem cells were not significant [ 183 ].…”

Construction of multifunctional porcine acellular dermal matrix hydrogel blended with vancomycin for hemorrhage control, antibacterial action, and tissue repair in infected trauma wounds

“…First, when the hydrogel encounters the wound, it changes from liquid to solid to form a physical barrier to prevent further blood flow. Its potential mechanism may be as described by Nyambat Batzaya [ 51 ]. Both the storage modulus (G′) and the loss modulus (G″) increase with the temperature rise from 10°C to 37°C in hydrogels, promoting the transformation from liquid phase to solid phase.…”

“…Extracellular matrix (ECM) hydrogel is a promising regenerative material that can effectively promote the repair of tissue defects. As previously reported [ 51 ], the entire ECM contains proteoglycans, growth factors, and matricellular proteins, including collagens, elastin, laminin, fibronectin, hyaluronan, heparan, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and thrombospondin. Among them, a major component of ECM is collagen.…”

Cell-Derived Extracellular Matrix for Tissue Engineering and Regenerative Medicine

“…Mechano-physical re-engineering could be achieved by culturing ECM-secreting cells in 3D sacrificial hydrogels (Yuan et al, 2018), on micro-molds (Schell et al, 2016), and micro-and nano-grooves (Ozguldez et al, 2018;Almici et al, 2020;Yang et al, 2020), forcing cell reorganization and leading to ECM assemblies with unique architectures (i.e., parallel fiber alignment). ECM postprocessing, such as cross-linking, could further alter ECM stiffness (Subbiah et al, 2016) or the overall presentation of CD-ECM.In particular, cross-linking of pepsin-solubilized CD-ECM with genipin resulted in the formation of hydrogels (Nyambat et al, 2020), Changes in biochemical and mechano-physical properties of the ECM let to changes in gene expression and behavior of reseeded cells (Kim et al, 2015;Ozguldez et al, 2018;Sart et al, 2020).…”

“…ECM postprocessing, such as cross-linking, could further alter ECM stiffness ( Subbiah et al, 2016 ) or the overall presentation of CD-ECM. In particular, cross-linking of pepsin-solubilized CD-ECM with genipin resulted in the formation of hydrogels ( Nyambat et al, 2020 ), Changes in biochemical and mechano-physical properties of the ECM let to changes in gene expression and behavior of reseeded cells ( Kim et al, 2015 ; Ozguldez et al, 2018 ; Sart et al, 2020 ).…”