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      Recent advances in photo-crosslinkable hydrogels for biomedical applications

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          Abstract

          Photo-crosslinkable hydrogels have recently attracted significant scientific interest. Their properties can be manipulated in a spatiotemporal manner through exposure to light to achieve the desirable functionality for various biomedical applications. This review article discusses the recent advances of the most common photo-crosslinkable hydrogels, including poly(ethylene glycol) diacrylate, gelatin methacryloyl and methacrylated hyaluronic acid, for various biomedical applications. We first highlight the advantages of photopolymerization and discuss diverse photosensitive systems used for the synthesis of photo-crosslinkable hydrogels. We then introduce their synthesis methods and review their latest state of development in biomedical applications, including tissue engineering and regenerative medicine, drug delivery, cancer therapies and biosensing. Lastly, the existing challenges and future perspectives of engineering photo-crosslinkable hydrogels for biomedical applications are briefly discussed.

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          Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

          Barbara J Klotz, Debby Gawlitta, Antoine J.W.P. Rosenberg … (2016)
          Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications.
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            A simple and high-resolution stereolithography-based 3D bioprinting system using visible light crosslinkable bioinks.

            Zongjie Wang, Raafa Abdulla, Benjamin Parker … (2015)
            Bioprinting is a rapidly developing technique for biofabrication. Because of its high resolution and the ability to print living cells, bioprinting has been widely used in artificial tissue and organ generation as well as microscale living cell deposition. In this paper, we present a low-cost stereolithography-based bioprinting system that uses visible light crosslinkable bioinks. This low-cost stereolithography system was built around a commercial projector with a simple water filter to prevent harmful infrared radiation from the projector. The visible light crosslinking was achieved by using a mixture of polyethylene glycol diacrylate (PEGDA) and gelatin methacrylate (GelMA) hydrogel with eosin Y based photoinitiator. Three different concentrations of hydrogel mixtures (10% PEG, 5% PEG + 5% GelMA, and 2.5% PEG + 7.5% GelMA, all w/v) were studied with the presented systems. The mechanical properties and microstructure of the developed bioink were measured and discussed in detail. Several cell-free hydrogel patterns were generated to demonstrate the resolution of the solution. Experimental results with NIH 3T3 fibroblast cells show that this system can produce a highly vertical 3D structure with 50 μm resolution and 85% cell viability for at least five days. The developed system provides a low-cost visible light stereolithography solution and has the potential to be widely used in tissue engineering and bioengineering for microscale cell patterning.
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              A liver-on-a-chip platform with bioprinted hepatic spheroids.

              Nupura Bhise, Vijayan Manoharan, Solange Massa … (2016)
              The inadequacy of animal models in correctly predicting drug and biothreat agent toxicity in humans has resulted in a pressing need for in vitro models that can recreate the in vivo scenario. One of the most important organs in the assessment of drug toxicity is liver. Here, we report the development of a liver-on-a-chip platform for long-term culture of three-dimensional (3D) human HepG2/C3A spheroids for drug toxicity assessment. The bioreactor design allowed for in situ monitoring of the culture environment by enabling direct access to the hepatic construct during the experiment without compromising the platform operation. The engineered bioreactor could be interfaced with a bioprinter to fabricate 3D hepatic constructs of spheroids encapsulated within photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. The engineered hepatic construct remained functional during the 30 days culture period as assessed by monitoring the secretion rates of albumin, alpha-1 antitrypsin, transferrin, and ceruloplasmin, as well as immunostaining for the hepatocyte markers, cytokeratin 18, MRP2 bile canalicular protein and tight junction protein ZO-1. Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.
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                Author and article information

                Journal
                Journal ID (publisher-id): BTN
                Title: BioTechniques
                Abbreviated Title: BioTechniques
                Abbreviated Title: BioTechniques
                Publisher: Future Science Ltd (London, UK )
                ISSN (Print): 0736-6205
                ISSN (Electronic): 1940-9818
                Publication date (Print): January 2019
                Publication date (Electronic): 15 January 2019
                Volume: 66
                Issue: 1
                Pages: 40-53
                Affiliations
                [1] 1Department of Mechanical Engineering, University of British Columbia, 2054–6250 Applied Science Lane, Vancouver, BC, V6T 1Z4, Canada
                [2] 2Centre for Blood Research, Life Sciences Centre, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada
                [3] 3Department of Chemical & Petroleum Engineering, Schulich School of Engineering, University of Calgary, Calgary, AB, T2N 1N4, Canada
                [4] 4Faculty of Medicine, University of Dundee, Dow Street, Dundee DD1 5EH, UK
                Author notes
                *Author for correspondence: janeruchoi@ 123456gmail.com
                **Author for correspondence: ronald_yong88@ 123456yahoo.com

                ‡Authors contributed equally

                Article
                DOI: 10.2144/btn-2018-0083
                PubMed ID: 30730212
                SO-VID: e8dd4748-7eac-4099-8d73-bac9d9a09a75
                Copyright © © 2019 Jane Ru Choi
                License:

                This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License

                History
                Date received : 14 June 2018
                Date accepted : 05 October 2018
                Date: 15 January 2019
                Categories
                Subject: Review

                ScienceOpen disciplines: General life sciences,Cell biology,Molecular biology,Biotechnology,Genetics,Life sciences
                Keywords: photo-crosslinkable hydrogels,cancer therapies,tissue engineering,drug delivery,biosensing
                Data availability:
                ScienceOpen disciplines: General life sciences, Cell biology, Molecular biology, Biotechnology, Genetics, Life sciences
                Keywords: photo-crosslinkable hydrogels, cancer therapies, tissue engineering, drug delivery, biosensing

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