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Liver diseases represent a considerable burden to patients and healthcare systems. Hydrogels play an important role in the engineering of soft tissues and may be useful for embedding hepatocytes for different therapeutic interventions or the development of in vitro models to study the pathogenesis of liver diseases or testing of drugs. Here, we developed two types of hydrogels by crosslinking hydrazide-functionalized gelatin with either oxidized dialdehyde hyaluronan or alginate through the formation of hydrazone bonds. Gel formulations were studied through texture analysis and rheometry, showing mechanical properties comparable to those of liver tissue while also demonstrating long-term stability. The biocompatibility of hydrogels and their ability to host hepatocytes was studied in vitro in comparison to pure gelatin hydrogels crosslinked by transglutaminase using the hepatocellular line HepG2. It was found that HepG2 cells could be successfully embedded in the hydrogels, showing no signs of gel toxicity and proliferating in a 3D environment comparable to pure transglutaminase cross-linked gelatin hydrogels used as control. Altogether, hydrazide gelatin in combination with oxidized polysaccharides makes stable in situ gelling systems for the incorporation of hepatocytes, which may pave the way for use in liver tissue engineering and drug testing. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a major cause of early death worldwide. By 2030, 14.5 million people will have end‐stage kidney disease (ESKD, or CKD stage 5), yet only 5.4 million will receive kidney replacement therapy (KRT) due to economic, social, and political factors. Even for those who are offered KRT by various means of dialysis, the life expectancy remains far too low. Observation: Researchers from different fields of artificial organs collaborate to overcome the challenges of creating products such as Wearable and/or Implantable Artificial Kidneys capable of providing long‐term effective physiologic kidney functions such as removal of uremic toxins, electrolyte homeostasis, and fluid regulation. A focus should be to develop easily accessible, safe, and inexpensive KRT options that enable a good quality of life and will also be available for patients in less‐developed regions of the world. Conclusions: Hence, it is required to discuss some of the limits and burdens of transplantation and different techniques of dialysis, including those performed at home. Furthermore, hurdles must be considered and overcome to develop wearable and implantable artificial kidney devices that can help to improve the quality of life and life expectancy of patients with CKD. [ABSTRACT FROM AUTHOR]

Surface coatings prepared by layer‐by‐layer technique permit loading of growth factors (GFs) and their spatially controlled release. Here, native chondroitin sulfate (nCS), oxidized CS (oCS100), or mixture of both (oCS50) are combined with collagen I (Col I) to fabricate polyelectrolyte multilayers (PEMs) that exhibit structural, mechanical, and biochemical cues like the natural extracellular‐matrix. The use of oCS enables intrinsic cross‐linking of PEM that offers higher stability, stiffness, and better control of bone morphogenetic protein‐2 (BMP‐2) release compared to nCS. oCS100 PEMs have enhanced stiffness, promote Col I fibrillization, and present BMP‐2 in a matrix‐bound manner. oCS50 PEMs show intermediate effects on osteogenesis, soft surface, high water content but also moderately slow BMP‐2 release profile. C2C12 myoblasts used for osteogenesis studies show that oCS PEMs are more stable and superior to nCS PEMs in supporting cell adhesion and spreading as well as in presenting BMP‐2 to the cells. oCS PEMs are triggering more osteogenesis as proved by the quantitative real‐time polymerase chain reaction, immune and histochemical staining. These findings show that intrinsic cross‐linking in oCS/Col I multilayers provides a successful tool to control GFs delivery and subsequent cell differentiation which opens new opportunities in regenerative therapies of bone and other tissues. [ABSTRACT FROM AUTHOR]

Hydrogels have been developed for different biomedical applications such as in vitro culture platforms, drug delivery, bioprinting and tissue engineering. Enzymatic cross-linking has many advantages for its ability to form gels in situ while being injected into tissue, which facilitates minimally invasive surgery and adaptation to the shape of the defect. It is a highly biocompatible form of cross-linking, which permits the harmless encapsulation of cytokines and cells in contrast to chemically or photochemically induced cross-linking processes. The enzymatic cross-linking of synthetic and biogenic polymers also opens up their application as bioinks for engineering tissue and tumor models. This review first provides a general overview of the different cross-linking mechanisms, followed by a detailed survey of the enzymatic cross-linking mechanism applied to both natural and synthetic hydrogels. A detailed analysis of their specifications for bioprinting and tissue engineering applications is also included. [ABSTRACT FROM AUTHOR]

The thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) is widely applied in the biomedical field particularly as thermoresponsive substrate for culture of cells. To be used as a stimuli-responsive coating for cell culture, combining PNIPAM with glycosaminoglycans might be an effective approach to improve its bioactivity. In this study, chitosan is grafted with PNIPAM moieties (PCHI) possessing a cloud point at 31 °C and used as a polycation to fabricate thermoresponsive polyelectrolyte multilayers (PEM) with the bioactive polyanion chondroitin sulfate (CS) at pH 4 by layer-by-layer technique. The in-situ investigation by surface plasmon resonance and quartz crystal microbalance with dissipation monitoring confirms that the formation of PEMs with CS can be achieved despite the bulky structure of PCHI at 25 °C. The stability of the PEMs is further improved at physiological pH 7.4 by chemical crosslinking using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide. Moreover, these PEMs exhibit de-swelling and swelling ability with different surface wettability in response to temperature, which triggers the adsorption and desorption of adhesive protein vitronectin on the PEMs. At 37 °C, the PEMs containing PNIPAM particularly associated with CS terminal layer supports protein adsorption and consequently enhances cell adhesion using multipotent murine stem cells. Overall, due to improved stability, crosslinked PNIPAM-modified biogenic multilayers are cytocompatible and hold great potential as culture substrate for different tissue cells and application in tissue engineering. [ABSTRACT FROM AUTHOR]