An important advantage of employing extracellular matrix (ECM)-derived biomaterials in tissue engineering is the ability to tailor the biochemical and biophysical microenvironment of the cells. This study aims to assess whether three-dimensional (3D) liver-derived ECM hydrogel (LEMgel) promotes physiological function of liver organoids generated by self-organization of human hepatocarcinoma cells together with human mesenchymal and endothelial cells. We have optimized the decellularization method to fabricate liver ECM derived from sheep to preserve the greatest content of glycosaminoglycans, collagen, laminin, and fibronectin in produced LEMgel. During gelation, complex viscoelasticity modulus of the LEMgel (3 mg/mL) increased from 186.7 to 1570.5 Pa and Tan Delta decreased from 0.27 to 0.18. Scanning electron microscopy (SEM) determined that the LEMgel had a pore size of 382 ± 71 µm. Hepatocarcinoma cells in the self-organized liver organoids in 3D LEMgel (LEMgel organoids) showed an epithelial phenotype and expressed ALB, CYP3A4, E-cadherin, and ASGPR. The LEMgel organoid had significant upregulation of transcripts of ALB, CYP3A4, CYP3A7, and TAT as well as downregulation of AFP compared to collagen type I- and hydrogel-free-organoids or organoids in solubilized LEM and 2D culture of hepatocarcinoma cells. Generated 3D LEMgel organoids had significantly more ALB and AAT secretion, urea production, CYP3A4 enzyme activity, and inducibility. In conclusion, 3D LEMgel enhanced the functional activity of self-organized liver organoids compared to traditional 2D, 3D, and collagen gel cultures. Our novel 3D LEMgel organoid could potentially be used in liver tissue engineering, drug discovery, toxicology studies, or bio-artificial liver fabrication.
One of the major problems in the treatment of cardiovascular diseases is the inability of myocardium to self-regenerate. Current therapies are unable to restore the heart's function after myocardial infarction. Myocardial tissue engineering is potentially a key approach to regenerate damaged heart muscle. Myocardial patches are applied surgically, whereas injectable hydrogels provide effective minimally invasive approaches to recover functional myocardium. These hydrogels are easily administered and can be either cell free or loaded with bioactive agents and/or cardiac stem cells, which may apply paracrine effects. The aim of this review is to investigate the advantages and disadvantages of injectable stem cell-laden hydrogels and highlight their potential applications for myocardium repair.
Despite progresses in tissue healing, repairing large bone defects remains an unmet challenge. Tissue engineering (TE) using porous scaffolds offers great promise in providing solutions by which bone healing can be increased, and the need for further surgical intervention can be reduced. Nonetheless, the successful performance of a porous scaffold depends on key structural factors including porosity, pore size, geometry, and interconnectivity. Herein, recent advancements on this topic are reviewed and the effects of fabrication methods on making potential scaffolds for advanced bone regeneration are discussed.The upward trend of population aging, increased numbers of accidents, sport injuries, trauma, and bone tumor resection are increasing the demand for substitutes to regenerate and/or repair damaged skeletal and dental bones. [1] Bone tissue poses a simple yet highly organized ultracomposition in which each portion plays a pivotal role in moderating the elasticity and strength of the bone. [2] The intrinsically dynamic bone tissue structure allows the restoration of damaged parts via the self-healing process. [3] This remodeling process is dependent on the dynamic equilibrium between the bone-forming (osteoblast) and bone-resorbing cells (osteoclast) during mechanical stimulation. [4] Nevertheless, this healing process is not sufficient for repairing massive and critical bone defects; thus, there is a need for drastic healing accelerators and substitutive or supportive therapeutics. [5] Specially, the regenerating of large bone defects is a serious and challenging clinical issue. To address the issue, different types of bone graft substitutes such as autografts, allografts, and xenografts are used. [6] These grafts, however, come with certain drawbacks, including donor site morbidity and limited supply. Moreover, aged persons cannot provide rich bone tissue for their own tissue replacement due to osteoporosis. [7] To address the limitations associated with natural bone-derived substitutes, biomaterials have been developed during recent decades. [8] Engineering biomaterials made it possible to simulate the bone microenvironment and construct programmable scaffolds for purposeful therapeutic procedures. Bioactive ceramic materials are favorable for bone tissue engineering (BTE) due to their resemblance to the mineral phase of bone, and direct bonding with host bone tissue without the formation of fibrous tissue. In addition, the variety in the chemical composition of bioceramics, particularly silicate-based ceramics (SiCa), can contribute to adjustments in mechanical properties, bioactivity, and biodegradability.A fundamental constituent of engineering tissue is the scaffold, which acts as the structural template providing a suitable substrate for cell proliferation, differentiation, and attachment resulting in new tissue formation. In tissue engineering (TE), the scaffold serves as the structural guide and the substrate for cell anchorage. The scaffold also contributes to the remodeling of the extracellular mat...
Myocardial infarction (MI) irreversibly injures the heart tissue. Cardiovascular tissue engineering has been developed as a promising therapeutic approach for post-MI repair. Previously, we discovered the ability of a polypyrrole (PPy)-incorporated cardiogel (CG) for improvement of maturity and functional synchrony of rat neonatal cardiomyocytes. Here, we used the cross-linked form of PPy-incorporated CG (CG-PPy), in order to improve electromechanical properties of scaffold, for application in cardiac progenitor cell (CPC) transplantation on post-MI rat hearts. Improved mechanical property and electrical conductivity (sixfold) were evident in the cross-linked CG-PPy (P1) compared to cross-linked CG (C1) scaffolds. Transplantation of CPC-loaded P1 (P1-CPC) resulted in substantial improvement of cardiac functional properties. Furthermore, lower fibrotic tissue and higher CPC retention were observed. The grafted cells showed cardiomyocyte characteristics when stained with human cardiac troponin T and connexin43 antibodies, while neovessel formation was similarly prominent. These findings highlight the therapeutic promise of the P1 scaffold as a CPC carrier for functional restoration of the heart post-MI.
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