Heparin hydrogel sandwich cultures of primary hepatocytes

Foster, Elena; You, Jungmok; Siltanen, Christian; Patel, Dipali; Haque, Amranul; Anderson, Leif S.; Revzin, Alexander

doi:10.1016/j.eurpolymj.2014.12.033

Cited by 39 publications

(29 citation statements)

References 56 publications

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“…Albumin and urea secretion are a hallmark indicator of hepatocyte health . During the 28 d long cultures, the daily albumin secretion rate (always expressed per 10 4 cells) progressively reduced on both multiwell plate and flat silicon controls without heparin coating.…”

Section: Resultsmentioning

confidence: 99%

Microengineered Bioartificial Liver Chip for Drug Toxicity Screening

Delalat

Cozzi

Ghaemi

et al. 2018

Adv Funct Materials

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Microfluidic 3D cell culture is a promising technology for the screening of drug toxicity profiles. In this study, a bioartificial liver consisting of a surfaceengineered microfluidic silicon chip with microtrenches mimicking hepatic sinusoids is shown to extend 3D primary hepatocyte culture and improve in vitro drug screening for hepatotoxicity, with respect to the state-of-the-art literature on this subject. Primary hepatocytes hosted in the 3D heparin-coated microtrenches (the bioartificial liver) secrete high levels of albumin and urea over 4 weeks. The cytotoxicity of common drugs, namely, acetaminophen, chlorpromazine, and tacrine, was assessed on primary hepatocytes both at day 1 and day 7. The results suggest that mimicking hepatic sinusoids using a microtrench format allows the maintenance of difficult-to-culture primary hepatocytes to be extended to 4 weeks and provides an alternative model to animal studies for the screening of the cytotoxicity of new drugs.

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Section: Resultsmentioning

confidence: 99%

Microengineered Bioartificial Liver Chip for Drug Toxicity Screening

Delalat

Cozzi

Ghaemi

et al. 2018

Adv Funct Materials

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“…The sandwich configuration is normally obtained by culturing hepatocytes on a hydrogel substrate, followed by covering the cells with another layer of hydrogel once the confluence was reached. Various types of materials have been used to develop the sandwich cultures, including the ECM‐based cultures, such as collagen/collagen, Matrigel/collagen, and decellularized connected liver tissue matrix (dECM); and semisynthetic hydrogels, such as heparin–PEG/heparin/PEG . Although conventional ECM‐based scaffolds more accurately resemble in vivo liver environment, there are several problems associated with the use of these gels in the sandwich configuration, including batch‐to‐batch variation, such as composition and mechanical properties (e.g., in the case of Matrigel and dECM), and inherent low mass transfer efficacy.…”

Section: In Vitro Liver Modelsmentioning

confidence: 99%

“…Researchers have attempted to explore solutions to mediate these problems using two main approaches: incorporate the sandwich culture into a perfusion device; and replace the ECM‐based matrix with synthetic or semisynthetic polymers with controllable physical and chemical properties. Recently, Revzin and co‐workers have developed photo‐crosslinkable heparin‐modified PEG hydrogels for culturing hepatocytes . Heparin molecules are a key component of ECM, which are a highly sulfated anionic polysaccharide with affinity to various growth factors and proteins.…”

Section: In Vitro Liver Modelsmentioning

confidence: 99%

“…The HGFs were added in both heparin–PEG and collagen sandwich systems to generate a head‐to‐head comparison. Results showed that liver‐specific functions in the heparin–PEG system are similar or even superior than the collagen sandwich system, and the cells have demonstrated survival over three weeks . Skardal et al investigated the effect of the incorporation of acellular liver ECM and whole (fresh) liver tissue into HA (Extracel) or heparin‐conjugated HA hydrogels, to create a semisynthetic ECM .…”

Section: In Vitro Liver Modelsmentioning

confidence: 99%

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Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models

Liaw

Guvendiren

2018

Adv Healthcare Materials

109

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There is a growing interest in engineering hydrogels for 3D tissue and disease models. The major motivation is to better mimic the physiological microenvironment of the disease and human condition. 3D tissue models derived from patients' own cells can potentially revolutionize the way treatment and diagnostic alternatives are developed. This requires development of tissue mimetic hydrogels with user defined and tunable properties. In this review article, a recent summary of 3D hydrogel platforms for in vitro tissue and disease modeling is given. Hydrogel design considerations and available hydrogel systems are summarized, followed by the types of currently available hydrogel models, such as bulk hydrogels, porous scaffolds, fibrous scaffolds, hydrogel microspheres, hydrogel sandwich systems, microwells, and 3D bioprinted constructs. Although hydrogels are utilized for a wide range of tissue models, this article focuses on liver and cancer models. This article also provides a detailed section on current challenges and future perspectives of hydrogel-based tissue models.

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“…Foster et al studied the use of heparin-containing hydrogels as scaffolds for the culture and for the maintenance of functional primary hepatocytes [60]. Thiolated heparin was conjugated to diacrylated PEG via a thiol-ene photocatalysed reaction.…”

Section: Hydrogel-glycan Conjugatesmentioning

confidence: 99%

Bioresponsive Hydrogels: Chemical Strategies and Perspectives in Tissue Engineering

Sgambato

Cipolla

Russo

2016

Preprint

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Disease, trauma, and aging account for a significant number of clinical disorders. Regenerative medicine is emerging as a very promising therapeutic option. The design and development of new cell-customised biomaterials able to mimic extracellular matrix (ECM) functionalities represents one of the major strategies to control the cell fate and stimulate tissue regeneration. Recently, hydrogels have received a considerable interest for their use in the modulation and control of cell fate during the regeneration processes. Several synthetic bioresponsive hydrogels are being developed in order to facilitate cell-matrix and cell-cell interactions. In this review, new strategies and future perspectives of such synthetic cell microenvironments will be highlighted.

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Heparin hydrogel sandwich cultures of primary hepatocytes

Cited by 39 publications

References 56 publications

Microengineered Bioartificial Liver Chip for Drug Toxicity Screening

Microengineered Bioartificial Liver Chip for Drug Toxicity Screening

Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models

Bioresponsive Hydrogels: Chemical Strategies and Perspectives in Tissue Engineering

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