Engineering the 3D Tumour microenvironment in vitro for Drug Discovery using Self-Assembling Peptide Hydrogels

Pancreatology ◽  
2020 ◽  
Vol 20 (8) ◽  
pp. e21
Author(s):  
A. Del Rio Hernandez ◽  
D. Lachowski ◽  
A. Miller
2010 ◽  
Vol 16 (2) ◽  
pp. 465-477 ◽  
Author(s):  
Paul W. Kopesky ◽  
Eric J. Vanderploeg ◽  
John S. Sandy ◽  
Bodo Kurz ◽  
Alan J. Grodzinsky

2020 ◽  
Author(s):  
Mostafa EzEldeen ◽  
Burak Toprakhisar ◽  
Denise Murgia ◽  
Nick Smisdom ◽  
Olivier Deschaume ◽  
...  

Abstract Tailored hydrogels mimicking the native extracellular environment could aid in overcoming the high variability in regenerative endodontics outcomes. This study aimed to evaluate the effect of the chemokine-binding and antimicrobial polymer, chlorite-oxidized oxyamylose (COAM), on the microstructural properties of fibrin and self-assembling peptide (SAP) hydrogels. Further, to assess the influence of the microstructural differences between the hydrogels on the in vitro behavior of dental pulp stem cells (DPSCs).Structural and mechanical characterization of the hydrogels with and without COAM was performed by atomic force microscopy and scanning electron microscopy to characterize their microstructure (roughness and fiber length, diameter, straightness and alignment) and by nanoindentation to measure their stiffness (elastic modulus). DPSCs were encapsulated in hydrogels with and without COAM. Cell viability and circularity was determined using confocal microscopy imaging, and proliferation was determined using DNA quantification. Inclusion of COAM did not alter the microstructure of the fibrin hydrogels at the fiber level, while affecting the SAP hydrogel microstructure (homogeneity) leading to fiber aggregation. The stiffness of the SAP hydrogels was 7-fold higher than the fibrin hydrogels. The viability and attachment of DPSCs and DNA content was significantly higher in fibrin hydrogels than in SAP hydrogels. The microstructural stability after COAM inclusion and the favorable DPSCs’ response observed in fibrin hydrogels suggest this system as a promising carrier for COAM and for application in endodontic regeneration.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mostafa EzEldeen ◽  
Burak Toprakhisar ◽  
Denise Murgia ◽  
Nick Smisdom ◽  
Olivier Deschaume ◽  
...  

AbstractTailored hydrogels mimicking the native extracellular environment could help overcome the high variability in outcomes within regenerative endodontics. This study aimed to evaluate the effect of the chemokine-binding and antimicrobial polymer, chlorite-oxidized oxyamylose (COAM), on the microstructural properties of fibrin and self-assembling peptide (SAP) hydrogels. A further goal was to assess the influence of the microstructural differences between the hydrogels on the in vitro behavior of human dental pulp stem cells (hDPSCs). Structural and mechanical characterization of the hydrogels with and without COAM was performed by atomic force microscopy and scanning electron microscopy to characterize their microstructure (roughness and fiber length, diameter, straightness, and alignment) and by nanoindentation to measure their stiffness (elastic modulus). Then, hDPSCs were encapsulated in hydrogels with and without COAM. Cell viability and circularity were determined using confocal microscopy, and proliferation was determined using DNA quantification. Inclusion of COAM did not alter the microstructure of the fibrin hydrogels at the fiber level while affecting the SAP hydrogel microstructure (homogeneity), leading to fiber aggregation. The stiffness of the SAP hydrogels was sevenfold higher than the fibrin hydrogels. The viability and attachment of hDPSCs were significantly higher in fibrin hydrogels than in SAP hydrogels. The DNA content was significantly affected by the hydrogel type and the presence of COAM. The microstructural stability after COAM inclusion and the favorable hDPSCs' response observed in fibrin hydrogels suggest this system as a promising carrier for COAM and application in endodontic regeneration.


2018 ◽  
Vol Volume 13 ◽  
pp. 6717-6733 ◽  
Author(s):  
Franziska Koch ◽  
Anne Wolff ◽  
Stephanie Mathes ◽  
Uwe Pieles ◽  
Sina Saxer ◽  
...  

2021 ◽  
Author(s):  
Adedamola Olayanju ◽  
Aline F Miller ◽  
Tahera Ansari ◽  
Christopher E. Goldring

AbstractA major challenge in advancing preclinical studies is the lack of robust in vitro culture systems that fully recapitulate the in vivo scenario together with limited clinical translational to humans. Organoids, as 3-dimensional (3D) self-replicating structures are increasingly being shown as powerful models for ex vivo experimentation in the field of regenerative medicine and drug discovery. Organoid formation requires the use of extracellular matrix (ECM) components to provide a 3D platform. However, the most commonly used ECM, essential for maintaining organoid growth is Matrigel and is derived from a tumorigenic source which limits its translational ability. PeptiGels® which are self-assembling peptide hydrogels present as alternatives to traditional ECM for use in 3D culture systems. Synthetic PeptiGels® are non-toxic, biocompatible, biodegradable and can be tuneable to simulate different tissue microenvironments. In this study, we validated the use of different types of PeptiGels® for porcine hepatic organoid growth. Hepatic organoids were assessed morphologically and using molecular techniques to determine the optimum PeptiGel® formulation. The outcome clearly demonstrated the ability of PeptiGel® to support organoid growth and offer themselves as a technological platform for 3D cultured physiologically and clinically relevant data.


Author(s):  
George C. Ruben ◽  
Kenneth A. Marx

Certain double stranded DNA bacteriophage and viruses are thought to have their DNA organized into large torus shaped structures. Morphologically, these poorly understood biological DNA tertiary structures resemble spermidine-condensed DNA complexes formed in vitro in the total absence of other macromolecules normally synthesized by the pathogens for the purpose of their own DNA packaging. Therefore, we have studied the tertiary structure of these self-assembling torus shaped spermidine- DNA complexes in a series of reports. Using freeze-etch, low Pt-C metal (10-15Å) replicas, we have visualized the microscopic DNA organization of both calf Thymus( CT) and linear 0X-174 RFII DNA toruses. In these structures DNA is circumferentially wound, continuously, around the torus into a semi-crystalline, hexagonal packed array of parallel DNA helix sections.


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