Dantrolene inhibits lysophosphatidylcholine-induced valve interstitial cell calcific nodule formation via blockade of the ryanodine receptor

Sylvester, Christopher B.; Amirkhosravi, Farshad; Bortoletto, Angelina S.; West, William B.; Connell, Jennifer P.; Grande‐Allen, K. Jane

doi:10.3389/fcvm.2023.1112965

Cited by 1 publication

(1 citation statement)

References 63 publications

(85 reference statements)

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“…The successful implementation of animal-derived gelatin sources in tissue engineering can be further limited due to the potential immunological risks and religious and regulatory restrictions. − Therefore, gelatin derived from human sources is anticipated to address these limitations. While potential pathogenic contamination or disease transmission can still occur, it is significantly reduced for human-derived biomaterials compared to their animal-derived analogues. − The use of commercially available human-derived GelMA has been published in the literature at an unreported degree of modification; , however, its propertiessuch as photocrosslinking efficiency and mechanical strengthhave not been modified or tuned to be readily used in a wide range of tissue engineering applications.…”

Section: Introductionmentioning

confidence: 99%

Development of Human-Derived Photocrosslinkable Gelatin Hydrogels for Tissue Engineering

Altunbek,

Gezek,

Buck

et al. 2023

Biomacromolecules

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Hydrogels are often used as biomimetic matrices for tissue regeneration. The source of the hydrogel is of utmost importance, as it affects the physicochemical characteristics and must be carefully selected to stimulate specific cell behaviors. Naturally derived polymeric biomaterials have inherent biological moieties, such as cell binding and protease cleavage sites, and thus can provide a suitable microenvironment for cells. Human-derived matrices can mitigate potential risks associated with the immune response and disease transmission from animal-derived biomaterials. In this article, we developed glycidyl methacrylate-modified human-derived gelatin (hGelGMA) hydrogels for use in tissue engineering applications. By adjusting the glycidyl methacrylate concentration in the reaction mixture, we synthesized hGelGMA with low, medium, and high degrees of modification referred to as hGelGMA-L, hGelGMA-M, and hGelGMA-H, respectively. The amount of polymeric networks in the hydrogels was increased proportionally with the degree of modification. This change has resulted in a decreasing trend in pore size, porosity, and consequent swelling ratio. Similarly, increasing the polymer concentration also exhibited slower enzymatic degradation. On the other hand, increasing the polymer concentration led to an improvement in mechanical properties, where the compressive moduli of hGelGMA-L, hGelGMA-M, and hGelGMA-H hydrogels have changed at 2.9 ± 1.0, 13.7 ± 0.9, and 26.4 ± 2.5 kPa, respectively. The cytocompatibility of hGelGMA was assessed by 3D encapsulation of human-derived cells, including human dermal fibroblasts (HDFs) and human mesenchymal stem cells (hMSCs), in vitro. Regardless of the degree of glycidyl methacrylate modification, the hGelGMA hydrogels preserved the viability of encapsulated cells and supported their growth and proliferation. HDF cells showed a higher metabolic activity in hGelGMA-H, while MSCs exhibited an increased metabolic activity when they were encapsulated in hGelGMA-M or hGelGMA-H. These results showed that photocrosslinkable human-derived gelatin-based hydrogels can be synthesized and their physical properties can be distinctly fine-tuned to different extents as a function of their degrees of modification depending on the needs of the target tissue. Due to its promising physical and biological properties, it is anticipated that hGelGMA can be utilized in a wide spectrum of tissue engineering applications.

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