| Reference | [1]. Polymers (Basel). 2020 Jul 3;12(7):1489. doi: 10.3390/polym12071489.<br />
The Photoinitiator Lithium Phenyl (2,4,6-Trimethylbenzoyl) Phosphinate with Exposure to 405 nm Light Is Cytotoxic to Mammalian Cells but Not Mutagenic in Bacterial Reverse Mutation Assays.<br />
Nguyen AK(1)(2), Goering PL(2), Elespuru RK(2), Sarkar Das S(2), Narayan RJ(1).<br />
Author information: (1)Joint UNC/NCSU Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695, USA. (2)Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.<br />
Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP) is a free radical photo-initiator used to initiate free radical chain polymerization upon light exposure, and is combined with gelatin methacryloyl (GelMA) to produce a photopolymer used in bioprinting. The free radicals produced under bioprinting conditions are potentially cytotoxic and mutagenic. Since these photo-generated free radicals are highly-reactive but short-lived, toxicity assessments should be conducted with light exposure. In this study, photorheology determined that 10 min exposure to 9.6 mW/cm2 405 nm light from an LED light source fully crosslinked 10 wt % GelMA with >3.4 mmol/L LAP, conditions that were used for subsequent cytotoxicity and mutagenicity assessments. These conditions were cytotoxic to M-1 mouse kidney collecting duct cells, a cell type susceptible to lithium toxicity. Exposure to ≤17 mmol/L (0.5 wt %) LAP without light was not cytotoxic; however, concurrent exposure to ≥3.4 mmol/L LAP and light was cytotoxic. No condition of LAP and/or light exposure evaluated was mutagenic in bacterial reverse mutation assays using S. typhimurium strains TA98, TA100 and E. coli WP2 uvrA. These data indicate that the combination of LAP and free radicals generated from photo-excited LAP is cytotoxic, but mutagenicity was not observed in bacteria under typical bioprinting conditions.<br />
DOI: 10.3390/polym12071489 PMCID: PMC7408440 PMID: 32635323<br />
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[2]. Materials (Basel). 2020 Oct 2;13(19):4401. doi: 10.3390/ma13194401.<br />
Photopolymerization-Based Synthesis of Uniform Magnetic Hydrogels and Colorimetric Glucose Detection.<br />
Mun SJ(1), Ko D(2), Kim HU(1), Han Y(2), Roh YH(1), Kim BG(2), Na HB(2), Bong KW(1).<br />
Author information: (1)Department of Chemical and Biological Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Korea. (2)Department of Chemical Engineering, Myongji University, Yongin, Gyeonggi-do 17058, Korea.<br />
Magnetic hydrogels have been commonly used in biomedical applications. As magnetite nanoparticles (MNPs) exhibit peroxidase enzyme-like activity, magnetic hydrogels have been actively used as signal transducers for biomedical assays. Droplet microfluidics, which uses photoinitiated polymerization, is a preferred method for the synthesis of magnetic hydrogels. However, light absorption by MNPs makes it difficult to obtain fully polymerized and homogeneous magnetic hydrogels through photoinitiated polymerization. Several methods have been reported to address this issue, but few studies have focused on investigating the light absorption properties of photoinitiators. In this study, we developed a simple method for the synthesis of poly(ethylene glycol) (PEG)-based uniform magnetic hydrogels that exploits the high ultraviolet absorption of a photoinitiator. Additionally, we investigated this effect on shape deformation and structural uniformity of the synthesized magnetic hydrogels. Two different photoinitiators, Darocur 1173 and lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP), with significantly different UV absorption properties were evaluated based on the synthesis of magnetic hydrogels. The magnetic characteristics of the PEG-stabilized MNPs in hydrogels were investigated with a vibrating sample magnetometer. Finally, the colorimetric detection of hydrogen peroxide and glucose was conducted based on the enzyme-like property of MNPs and repeated several times to observe the catalytic activity of the magnetic hydrogels.<br />
DOI: 10.3390/ma13194401 PMCID: PMC7579115 PMID: 33023165<br />
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[3]. J Biomater Sci Polym Ed. 2021 Jun;32(8):1057-1071. doi: 10.1080/09205063.2021.1899888. Epub 2021 Mar 23.<br />
Methacrylated pullulan/polyethylene (glycol) diacrylate composite hydrogel for cartilage tissue engineering.<br />
Qin X(1), He R(1), Chen H(1), Fu D(1), Peng Y(1), Meng S(2), Chen C(2), Yang L(1).<br />
Author information: (1)Center for Joint Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China. (2)College of Medical Informatics, Chongqing Medical University, Chongqing, China.<br />
Pullulan hydrogels are widely used in tissue engineering and drug delivery. However, these hydrogels do not meet the requirements of articular cartilage repair because of their fast degradation rate and poor mechanical strength. Herein, we fabricated a hybrid hydrogel system by combining pullulan with synthetic polymers polyethylene (glycol) diacrylate (PEGDA). In this study, pullulan was modified with methacrylic anhydride (MA) to obtain photo-crosslinkable methacrylated pullulan (PulMA). Moreover, the lithium phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP) was used as a water-soluble UV photoinitiator to form the PulMA/PEGDA hydrogel by photopolymerization strategy. Compared with the pure PulMA hydrogel, the increase of PEGDA concentration led to a slower degradation rate and an increase of residual mass from 63.9% to 86.8%. There was about 8-fold increase in storage modulus (G') (reach to 16.0 × 103 Pa) and 13-fold increase in compressive modulus (reach to 1.17 ± 0.17 MPa) with increasing the concentration of PEGDA to 15% (w/v) in the hydrogel. In cell culture in vitro, the rabbit's mesenchymal stem cells (MSCs) encapsulated in the PulMA/PEGDA hydrogel could adhere and proliferate, indicating that the PulMA/PEGDA hydrogel had a good biocompatibility. Furthermore, the hydrogels supported glycosaminoglycan (GAG) synthesis, and chondrogenic phenotype of MSCs with TGF-β3-containing chondrogenic medium. This study demonstrated that the photo-crosslinking PulMA/PEGDA hydrogels, with good mechanical properties and slow degradation rate are promising scaffolds for cartilage repair and regeneration.<br />
DOI: 10.1080/09205063.2021.1899888 PMID: 33685369<br />
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[4]. Macromol Biosci. 2019 Jun;19(6):e1900098. doi: 10.1002/mabi.201900098. Epub 2019 Apr 26.<br />
Visible Light Cross-Linking of Gelatin Hydrogels Offers an Enhanced Cell Microenvironment with Improved Light Penetration Depth.<br />
Lim KS(1)(2)(3), Klotz BJ(4), Lindberg GCJ(1)(2), Melchels FPW(5), Hooper GJ(1), Malda J(6)(7)(8), Gawlitta D(4), Woodfield TBF(1)(2)(3).<br />
Author information: (1)Christchurch Regenerative Medicine and Tissue Engineering (CReaTE) Group, Department of Orthopaedic Surgery and Musculoskeletal Medicine, University of Otago Christchurch, Christchurch, 8011, New Zealand. (2)Medical Technologies Centre of Research Excellence, Auckland, 1010, New Zealand. (3)Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, 1010, New Zealand. (4)Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, PO 85500, Utrecht, GA, 3508, The Netherlands. (5)Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, United Kingdom. (6)Regenerative Medicine Center Utrecht, PO 85500, Utrecht, GA, 3508, The Netherlands. (7)University Medical Center Utrecht, PO 85500, Utrecht, GA, 3508, The Netherlands. (8)Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, Utrecht, CM, 3584, The Netherlands.<br />
In this study, the cyto-compatibility and cellular functionality of cell-laden gelatin-methacryloyl (Gel-MA) hydrogels fabricated using a set of photo-initiators which absorb in 400-450 nm of the visible light range are investigated. Gel-MA hydrogels cross-linked using ruthenium (Ru) and sodium persulfate (SPS), are characterized to have comparable physico-mechanical properties as Gel-MA gels photo-polymerized using more conventionally adopted photo-initiators, such as 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propan-1-one (Irgacure 2959) and lithium phenyl(2,4,6-trimethylbenzoyl) phosphinate (LAP). It is demonstrated that the Ru/SPS system has a less adverse effect on the viability and metabolic activity of human articular chondrocytes encapsulated in Gel-MA hydrogels for up to 35 days. Furthermore, cell-laden constructs cross-linked using the Ru/SPS system have significantly higher glycosaminoglycan content and re-differentiation capacity as compared to cells encapsulated using I2959 and LAP. Moreover, the Ru/SPS system offers significantly greater light penetration depth as compared to the I2959 system, allowing thick (10 mm) Gel-MA hydrogels to be fabricated with homogenous cross-linking density throughout the construct. These results demonstrate the considerable advantages of the Ru/SPS system over traditional UV polymerizing systems in terms of clinical relevance and practicability for applications such as cell encapsulation, biofabrication, and in situ cross-linking of injectable hydrogels.<br />
DOI: 10.1002/mabi.201900098 PMID: 31026127 [Indexed for MEDLINE]<br />
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[5]. Polymers (Basel). 2020 Jul 3;12(7):1489. doi: 10.3390/polym12071489.<br />
The Photoinitiator Lithium Phenyl (2,4,6-Trimethylbenzoyl) Phosphinate with Exposure to 405 nm Light Is Cytotoxic to Mammalian Cells but Not Mutagenic in Bacterial Reverse Mutation Assays.<br />
Nguyen AK(1)(2), Goering PL(2), Elespuru RK(2), Sarkar Das S(2), Narayan RJ(1).<br />
Author information: (1)Joint UNC/NCSU Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695, USA. (2)Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.<br />
Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP) is a free radical photo-initiator used to initiate free radical chain polymerization upon light exposure, and is combined with gelatin methacryloyl (GelMA) to produce a photopolymer used in bioprinting. The free radicals produced under bioprinting conditions are potentially cytotoxic and mutagenic. Since these photo-generated free radicals are highly-reactive but short-lived, toxicity assessments should be conducted with light exposure. In this study, photorheology determined that 10 min exposure to 9.6 mW/cm2 405 nm light from an LED light source fully crosslinked 10 wt % GelMA with >3.4 mmol/L LAP, conditions that were used for subsequent cytotoxicity and mutagenicity assessments. These conditions were cytotoxic to M-1 mouse kidney collecting duct cells, a cell type susceptible to lithium toxicity. Exposure to ≤17 mmol/L (0.5 wt %) LAP without light was not cytotoxic; however, concurrent exposure to ≥3.4 mmol/L LAP and light was cytotoxic. No condition of LAP and/or light exposure evaluated was mutagenic in bacterial reverse mutation assays using S. typhimurium strains TA98, TA100 and E. coli WP2 uvrA. These data indicate that the combination of LAP and free radicals generated from photo-excited LAP is cytotoxic, but mutagenicity was not observed in bacteria under typical bioprinting conditions.<br />
DOI: 10.3390/polym12071489 PMCID: PMC7408440 PMID: 32635323
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