scholarly journals 3D-Printable Hierarchical Nanogel-GelMA Composite Hydrogel System

Polymers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 2508
Author(s):  
Guangyue Zu ◽  
Marnix Meijer ◽  
Olga Mergel ◽  
Heng Zhang ◽  
Patrick van Rijn

The strength of the extracellular matrix (ECM) is that it is hierarchical in terms of matrix built-up, matrix density and fiber structure, which allows for hormones, cytokines, and other small biomolecules to be stored within its network. The ECM-like hydrogels that are currently used do not possess this ability, and long-term storage, along with the need for free diffusion of small molecules, are generally incompatible requirements. Nanogels are able to fulfill the additional requirements upon successful integration. Herein, a stable hierarchical nanogel–gelatin methacryloyl (GelMA) composite hydrogel system is provided by covalently embedding nanogels inside the micropore network of GelMA hydrogel to allow a controlled local functionality that is not found in a homogenous GelMA hydrogel. Nanogels have emerged as a powerful tool in nanomedicine and are highly versatile, due to their simplicity of chemical control and biological compatibility. In this study, an N-isopropylacrylamide-based nanogel with primary amine groups on the surface was modified with methacryloyl groups to obtain a photo-cross-linking ability similar to GelMA. The nanogel-GelMA composite hydrogel was formed by mixing the GelMA and the photo-initiator within the nanogel solution through UV irradiation. The morphology of the composite hydrogel was observed by scanning electron microscopy, which clearly showed the nanogel wrapped within the GelMA network and covering the surface of the pore wall. A release experiment was conducted to prove covalent bonding and the stability of the nanogel inside the GelMA hydrogel. In addition, 3D printability studies showed that the nanogel-GelMA composite ink is printable. Therefore, the suggested stable hierarchical nanogel-GelMA composite hydrogel system has great potential to achieve the in situ delivery and controllable release of bioactive molecules in 3D cell culture systems.

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4166
Author(s):  
Saliha Erikci ◽  
Patricia Mundinger ◽  
Heike Boehm

In this study, we demonstrate that small charged molecules (NH4+, GluA+, dHA+) can form physical cross-links between hyaluronan chains, facilitating polymerization reactions between synthetically introduced thiol groups (HA-DTPH). These hybrid hydrogels can be obtained under physiological conditions ideally suited for 3D cell culture systems. The type and concentration of a physical crosslinker can be adjusted to precisely tune mechanical properties as well as degradability of the desired hydrogel system. We analyze the influence of hydrogen bond formation, concentration and additional ionic interactions on the polymerization reaction of HA-DTPH hydrogels and characterize the resulting hydrogels in regard to mechanical and biocompatibility aspects.


2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Laurence Finot ◽  
Eric Chanat ◽  
Frederic Dessauge

AbstractIn vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.


Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2354
Author(s):  
Jimmy Jiun-Ming Su ◽  
Chih-Hsin Lin ◽  
Hsuan Chen ◽  
Shyh-Yuan Lee ◽  
Yuan-Min Lin

Gelatin methacryloyl (GelMA) hydrogel is a photopolymerizable biomaterial widely used for three-dimensional (3D) cell culture due to its high biocompatibility. However, the drawback of GelMA hydrogel is its poor mechanical properties, which may compromise the feasibility of biofabrication techniques. In this study, a cell-laden GelMA composite hydrogel with a combination incorporating silanized hydroxyapatite (Si-HAp) and a simple and harmless visible light crosslinking system for this hydrogel were developed. The incorporation of Si-HAp into the GelMA hydrogel enhanced the mechanical properties of the composite hydrogel. Moreover, the composite hydrogel exhibited low cytotoxicity and promoted the osteogenic gene expression of embedded MG63 cells and Human bone marrow mesenchymal stem cells (hBMSCs). We also established a maskless lithographic method to fabricate a defined 3D structure under visible light by using a digital light processing projector, and the incorporation of Si-HAp increased the resolution of photolithographic hydrogels. The GelMA-Si-HAp composite hydrogel system can serve as an effective biomaterial in bone regeneration.


2020 ◽  
pp. 201-236
Author(s):  
Omaer Syed ◽  
Chris Chapman ◽  
Catalina Vallejo-Giraldo ◽  
Martina Genta ◽  
Josef Goding ◽  
...  

2020 ◽  
pp. 193229682096365
Author(s):  
Stefan Pleus ◽  
Guido Freckmann ◽  
Annette Baumstark ◽  
Cornelia Haug

Background: Conflicting information is available regarding the stability of glucose concentrations in frozen plasma samples. Clinical trials could benefit from such long-term storage because it would allow usage of a central laboratory with higher-quality laboratory analyzers in contrast to mobile analyzers in a decentralized setting. Methods: In this study, venous blood samples were collected in lithium-heparin gel tubes. Plasma was separated immediately after blood was drawn, and from each of the 21 plasma samples, 6 aliquots were prepared for measurement at 6 time points: immediately and after 2, 4, 6, 8, and 12 weeks. Between sampling and measurement, aliquots were stored at less than −20°C. Transport on dry ice was simulated by placing aliquots in a −80°C freezer for 5 days between weeks 8 and 12. Measurements were performed on a hexokinase-based laboratory analyzer. Average relative differences and corresponding 99% confidence intervals (CIs) were calculated between the stored aliquots’ and the immediately measured aliquots’ glucose concentrations. Glucose concentrations were deemed stable as long as average relative differences were ≤±2.5%. Results: Over the whole 12-weeks duration, the largest average relative difference was −1.82% (99% CI: –2.25% to −1.39%). Shorter storage durations tended to lead to less bias. Conclusion: In this study, the stability of glucose concentrations in frozen plasma samples obtained with lithium-heparin gel tubes could be shown for up to 12 weeks. Future studies should be performed to assess whether this is independent of the glucose analyzer and the type of sampling tube used.


2013 ◽  
Vol 26 (6) ◽  
pp. 865-872 ◽  
Author(s):  
Daniel D. McKinnon ◽  
Dylan W. Domaille ◽  
Jennifer N. Cha ◽  
Kristi S. Anseth

2008 ◽  
Vol 1 (1) ◽  
pp. 67-78 ◽  
Author(s):  
M. Hafner ◽  
M. Sulyok ◽  
R. Schuhmacher ◽  
C. Crews ◽  
R. Krska

In this paper the stability and degree of epimerisation of six major ergot alkaloids at three different temperature levels (-20 °C, +4 °C and +20 °C) over periods of 18 hours and six weeks is reported for the first time. The behaviour of ergometrine, ergocornine, ergocristine, α-ergocryptine, ergosine and ergotamine was thoroughly studied in seven solvents which are employed for the preparation of calibrants and extraction mixtures, respectively. Moreover, the stability of the ergot alkaloids was tested in different cereal extracts (rye, wheat, barley, oats) for 1, 2 and 6 days. Of the toxins tested, the ergopeptide-type toxins ergosine, ergotamine, ergocornine, α-ergocryptine and ergocristine showed similar behaviour patterns. The simple lysergic acid derivative ergometrine was more stable and showed hardly any epimerisation to ergometrinine, with the sum of both epimers remaining constant in all seven solvents. The ergopeptides tested show variable epimerisation tendencies, and were also less stable during six weeks at 20 °C. Ergosine showed the highest degree of epimerisation (43% after 6 weeks at 20 °C). In general, the order of epimerisation promotion was methanol/dichloromethane > acetonitrile/buffer > extraction mix > stabilising solution > acetonitrile >> chloroform. Long-term storage at room temperature can only be carried out in chloroform, which showed no epimerisation for all toxins even at 20 °C and also kept the sum of R and S forms constant, which indicates no formation of aci-epimers or other degradation products. Long-term storage of ergot alkaloids in acetonitrile, the most convenient solvent with respect to HPLC analysis, should be carried out at temperatures of -20 °C or below. The constant epimer ratio of all ergot alkaloids in the extraction mixture acetonitrile/ammonium carbonate buffer (200 mg/l; 92:8, v/v) during an HPLC run (18 hours) demonstrates the stability of the toxins in this extraction mixture.


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