In vitro assessment of inflammatory skin potential of poly(methyl methacrylate) at non-cytotoxic concentrations.
NIH3T3
inflammatory skin potential
non-cytotoxic concentration
poly(methyl methacrylate)
reconstructed human epidermis
Journal
Journal of biomedical materials research. Part A
ISSN: 1552-4965
Titre abrégé: J Biomed Mater Res A
Pays: United States
ID NLM: 101234237
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
10
06
2023
received:
18
04
2023
accepted:
18
07
2023
medline:
13
9
2023
pubmed:
17
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
Poly(methyl methacrylate) (PMMA) is considered an attractive substrate material for fabricating wearable skin sensors such as fitness bands and microfluidic devices. Despite its widespread use, inflammatory and allergic responses have been attributed to the use of this material. Therefore, the main objective of this study was to obtain a comprehensive understanding of potential biological effects triggered by PMMA at non-cytotoxic concentrations using in vitro models of NIH3T3 fibroblasts and reconstructed human epidermis (RhE). It was hypothesized that concentrations that do not reduce cell viability are sufficient to activate pathways of inflammatory processes in the skin. The study included cytotoxicity, cell metabolism, cytokine quantification, histopathological, and gene expression analyses. The NIH3T3 cell line was used as a testbed for screening cell toxicity levels associated with the concentration of PMMA with different molecular weights (MWs) (i.e., MW ~5,000 and ~15,000 g/mol). The lower MW of PMMA had a half-maximal inhibitory concentration (IC
Substances chimiques
Polymethyl Methacrylate
9011-14-7
Cytokines
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1822-1832Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Jin H, Abu-Raya YS, Haick H. Advanced materials for health monitoring with skin-based wearable devices. Adv Healthc Mater. 2017;6(11):1700024. doi:10.1002/adhm.201700024
Smuck M, Odonkor CA, Wilt JK, Schmidt N, Swiernik MA. The emerging clinical role of wearables: factors for successful implementation in healthcare. Nat Partn J. 2021;4(1):45. doi:10.1038/s41746-021-00418-3
Ates HC, Nguyen PQ, Gonzalez-Macia L, et al. End-to-end design of wearable sensors. Nat Rev Mater. 2022;7(11):907. doi:10.1038/S41578-022-00460-X
Guk K, Han G, Lim J, et al. Evolution of wearable devices with real-time disease monitoring for personalized healthcare. Nanomaterials. 2019;9(6):1-23. doi:10.3390/nano9060813
Ates HC, Brunauer A, von Stetten F, et al. Integrated devices for non-invasive diagnostics. Adv Funct Mater. 2021;31(15):2010388. doi:10.1002/ADFM.202010388
Harito C, Utari L, Putra BR, et al. Review-The development of wearable polymer-based sensors: perspectives. J Electrochem Soc. 2020;167(3):037566. doi:10.1149/1945-7111/AB697C
Anastasova S, Crewther B, Bembnowicz P, et al. A wearable multisensing patch for continuous sweat monitoring. Biosens Bioelectron. 2017;93:139-145. doi:10.1016/J.BIOS.2016.09.038
Chung M, Fortunato G, Radacsi N. Wearable flexible sweat sensors for healthcare monitoring: A review. J R Soc Interface. 2019;16(159):20190217. doi:10.1098/RSIF.2019.0217
Dias D, Cunha JPS. Wearable health devices-Vital sign monitoring, systems and Technologies. Sensors (Basel). 2018;18(8):2414. doi:10.3390/s18082414
Khatsenko K, Khin Y, Maibach H. Allergic contact dermatitis to components of wearable adhesive health devices. Am Contact Dermat Soc. 2020;31(5):283-286. doi:10.1097/DER.0000000000000575
Zhao Y, Huang X. Mechanisms and materials of flexible and stretchable skin sensors. Micromachines (Basel). 2017;8(3):69. doi:10.3390/MI8030069
Ullah H, Wahab MA, Will G, et al. Recent advances in stretchable and wearable capacitive electrophysiological sensors for long-term health monitoring. Biosensors. 2022;12(8):630. doi:10.3390/BIOS12080630
Matellan C, Del Río Hernández AE. Cost-effective rapid prototyping and assembly of poly(methyl methacrylate) microfluidic devices. Sci Rep. 2018;8(1):6971. doi:10.1038/S41598-018-25202-4
Trinh KTL, Thai DA, Chae WR, Lee NY. Rapid fabrication of poly(methyl methacrylate) devices for Lab-Ona-Chip applications using acetic acid and UV treatment. ACS Omega. 2020;5(28):17396-17404. doi:10.1021/ACSOMEGA.0C01770/SUPPL_FILE/AO0C01770_SI_001.PDF
Khan S, Ali S, Khan A, Bermak A. Wearable printed temperature sensors: short review on latest advances for biomedical applications. IEEE Rev Biomed Eng. 2023;16:152-170. doi:10.1109/RBME.2021.3121480
Liga A, Morton JAS, Kersaudy-Kerhoas M. Safe and cost-effective rapid-prototyping of multilayer PMMA microfluidic devices. Microfluid Nanofluid. 2016;20(12):1-12. doi:10.1007/S10404-016-1823-1/TABLES/1
Kitayama T, Shinozaki T, Masuda E, Yamamoto M, Hatada K. Highly syndiotactic poly(methyl methacrylate) with narrow molecular weight distribution formed by tert-butyllithium-trialkylaluminium in toluene. Polym Bull. 1988;20(6):505-510. doi:10.1007/BF00263663/METRICS
Ren JM, Knight AS, Van Ravensteijn BGP, et al. DNA-inspired Strand-exchange for switchable PMMA-based supramolecular morphologies. J Am Chem Soc. 2019;141(6):2630-2635. doi:10.1021/JACS.8B12964/SUPPL_FILE/JA8B12964_SI_001.PDF
Feuser PE, Bubniak LDS, Bodack CDN, et al. In vitro cytotoxicity of poly(methyl methacrylate) nanoparticles and nanocapsules obtained by miniemulsion polymerization for drug delivery application. J Nanosci Nanotechnol. 2016;16(7):7669-7676. doi:10.1166/JNN.2016.11610
Feuser PE, Gaspar PC, Ricci-Júnior E, et al. Synthesis and characterization of poly(methyl methacrylate) Pmma and evaluation of cytotoxicity for biomedical application. Macromol Symp. 2014;343(1):65-69. doi:10.1002/masy.201300194
Bastidas-Coral AP, Bakker AD, Kleverlaan CJ, Hogervorst JMA, Klein-Nulend J, Forouzanfar T. Polymethyl methacrylate does not adversely affect the osteogenic potential of human adipose stem cells or primary osteoblasts. J Biomed Mater Res B Appl Biomater. 2020;108(4):1536-1545. doi:10.1002/JBM.B.34501
International Organization for Standardization. ISO 10993-5: Biological Evaluation of Medical Devices-Part 5: Tests for in Vitro Cytotoxicity. 2009.
Emergency Care Research Institute (ECRI). Polymethyl Methacrylate Safety Profile Report for the U.S. FDA Center for Devices and Radiological Health. 2021.
de Leao RS, Maior JRS, de Lemos CAA, et al. Complications with PMMA compared with other materials used in cranioplasty: A systematic review and meta-analysis. Braz Oral Res. 2018;32(e31):1-12. doi:10.1590/1807-3107bor-2018.vol32.0031
Wesp D, Krenzlin H, Jankovic D, et al. Analysis of PMMA versus CaP titanium-enhanced implants for cranioplasty after decompressive craniectomy: A retrospective observational cohort study. Neurosurg Rev. 2022;45(6):3647-3655. doi:10.1007/S10143-022-01874-5/FIGURES/3
Limongi RM, Tao J, Borba A, et al. Complications and Management of polymethylmethacrylate (PMMA) injections to the midface. Aesthet Surg J. 2016;36(2):132-135. doi:10.1093/ASJ/SJV195
Pacheco K, Barker L, Mondello G, Mayer A. Patterns of methyl methacrylate sensitization in patients before or after joint replacement. J Allergy Clin Immunol. 2020;145(2):AB131. doi:10.1016/J.JACI.2019.12.521
Balduzzi M, Diociaiuti M, De Berardis B, Paradisi S, Paoletti L. In vitro effects on macrophages induced by noncytotoxic doses of silica particles possibly relevant to ambient exposure. Environ Res. 2004;96(1):62-71. doi:10.1016/J.ENVRES.2003.11.004
Zhang T, Zhang Q, Guo J, et al. Non-cytotoxic concentrations of acetaminophen induced mitochondrial biogenesis and antioxidant response in HepG2 cells. Environ Toxicol Pharmacol. 2016;46:71-79. doi:10.1016/J.ETAP.2016.06.030
Zarei MH, Pourahmad J, Aghvami M, Soodi M, Nassireslami E. Lead acetate toxicity on human lymphocytes at non-cytotoxic concentrations detected in human blood. Main gr Met Chem. 2017;40(5-6):105-112. doi:10.1515/MGMC-2017-0023/MACHINEREADABLECITATION/RIS
Mellati A, Valizadeh Kiamahalleh M, Dai S, Bi J, Jin B, Zhang H. Influence of polymer molecular weight on the in vitro cytotoxicity of poly (N-isopropylacrylamide). Mater Sci Eng C. 2016;59:509-513. doi:10.1016/J.MSEC.2015.10.043
Seneviratne S, Hu Y, Nguyen T, et al. A survey of wearable devices and challenges. IEEE Commun Surv Tutorials. 2017;19(4):2573-2620. doi:10.1109/COMST.2017.2731979
Engel JM, Chakravarthy BLN, Rothwell D, Chavan A. SEEQ™ MCT wearable sensor performance correlated to skin irritation and temperature. Annu Int Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Annu Int Conf. 2015;2015:2030-2033. doi:10.1109/EMBC.2015.7318785
Li D. Lifetime and Degradation Studies of Poly (Methyl Methacrylate) (PMMA) via Data-Driven Methods. Case Western Reserve University; 2020.
Abbott A. Cell culture: Biology's new dimension. Nature. 2003;424(6951):870-872. doi:10.1038/424870A
Chaklader M. Stem cells: stem cells in toxicology. Ref Modul Biomed Sci. 2023;1-8. doi:10.1016/B978-0-12-824315-2.00673-4
Jensen C, Teng Y. Is it time to start transitioning from 2D to 3D cell culture? Front Mol Biosci. 2020;7:33. doi:10.3389/FMOLB.2020.00033
Kapałczyńska M, Kolenda T, Przybyła W, et al. 2D and 3D cell cultures - A comparison of different types of cancer cell cultures. Arch Med Sci. 2018;14(4):910-919. doi:10.5114/AOMS.2016.63743
Organization for Economic Co-operation and Development (OECD). Test No. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method; OECD Guidelines for the Testing of Chemicals, Section 4. OECD; 2013. doi:10.1787/9789264203884-en
International Organization for Standardization. ISO 10993-23: Tests for Irritation; Switzerland. 2021.
Drazen A, Dreber A, Ozbay EY, Snowberg E. Journal-based replication of experiments: an application to “Being Chosen to Lead”. J Public Econ. 2021;202:104482. doi:10.1016/J.JPUBECO.2021.104482
Arezski N, Cobb A, Williams A, Brown B. Dermal Compositions Containing Unatural Hygroscopic Amino Acids. WO 2014/072747 A1, 2014.
Pellevoisin C, Videau C, Briotet D, et al. SkinEthic™ RHE for in vitro evaluation of skin irritation of medical device extracts. Toxicol In Vitro. 2018;50:418-425. doi:10.1016/J.TIV.2018.01.008
Misiak P, Niemirowicz- Laskowska K, Markiewicz KH, et al. Evaluation of cytotoxic effect of cholesterol end-capped poly(N-isopropylacrylamide)s on selected normal and neoplastic cells. Int J Nanomedicine. 2020;15:7263-7278. doi:10.2147/IJN.S262582
Biondi O, Motta S, Mosesso P. Low molecular weight polyethylene glycol induces chromosome aberrations in Chinese hamster cells cultured in vitro. Mutagenesis. 2002;17(3):261-264. doi:10.1093/MUTAGE/17.3.261
Monnery BD, Wright M, Cavill R, et al. Cytotoxicity of polycations: relationship of molecular weight and the hydrolytic theory of the mechanism of toxicity. Int J Pharm. 2017;521(1-2):249-258. doi:10.1016/J.IJPHARM.2017.02.048
Harris J, Daugulis AJ. Biocompatibility of low molecular weight polymers for two-phase partitioning bioreactors; biocompatibility of low molecular weight polymers for two-phase partitioning bioreactors. Biotechnol Bioeng. 2015;112:2450-2458. doi:10.1002/bit.25664/abstract
Greim H. Methyl methacrylate. The MAK-Collection for Occupational Health and Safety. Vol 26. John Wiley & Sons, Ltd; 2012:230-256. doi:10.1002/3527600418.MB8062E0026
Ertel SI, Ratner BD, Kaul A, Schway MB, Horbett' TA. In vitro study of the intrinsic toxicity of synthetic surfaces to cells. J Biomed Mater Res. 1994;6(28):667-675. doi:10.1002/jbm.820280603
Smolina N, Bruton J, Kostareva A, Sejersen T. Assaying mitochondrial respiration as an indicator of cellular metabolism and fitness. Methods Mol Biol. 2017;1601:79-87. doi:10.1007/978-1-4939-6960-9_7
Technologies A. Agilent Technologies Agilent Seahorse XF Cell Mito Stress Test Kit User Guide; Wilmington. 2019.
Gu X, Ma Y, Liu Y, Wan Q. Measurement of mitochondrial respiration in adherent cells by seahorse XF96 cell Mito stress test. STAR Protoc. 2021;2(1):100245. doi:10.1016/J.XPRO.2020.100245
Altintas MM, DiBartolo S, Tadros L, Samelko B, Wasse H. Metabolic changes in peripheral blood mononuclear cells isolated from patients with end stage renal disease. Front Endocrinol (Lausanne). 2021;12:114. doi:10.3389/FENDO.2021.629239/BIBTEX
Marchetti P, Fovez Q, Germain N, Khamari R, Kluza J. Mitochondrial spare respiratory capacity: mechanisms, regulation, and significance in non-transformed and cancer cells. FASEB J. 2020;34(10):13106-13124. doi:10.1096/FJ.202000767R
Diaz-Vegas A, Sanchez-Aguilera P, Krycer JR, et al. Is mitochondrial dysfunction a common root of noncommunicable chronic diseases? Endocr Rev. 2020;41(3):491-517. doi:10.1210/ENDREV/BNAA005
Zhu J, Thompson CB. Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol. 2019;20(7):436-450. doi:10.1038/S41580-019-0123-5
Deberardinis RJ, Thompson CB. Cellular metabolism and disease: what do metabolic outliers teach us? Cell. 2012;148(6):1132-1144. doi:10.1016/J.CELL.2012.02.032
Teh JT, Zhu WL, Newgard CB, Casey PJ, Wang M. Respiratory capacity and reserve predict cell sensitivity to mitochondria inhibitors: mechanism-based markers to identify metformin-responsive cancers. Mol Cancer Ther. 2019;18(3):693-705. doi:10.1158/1535-7163.MCT-18-0766
Roche HM, Roche M. Metabolism and inflammation: new synergies and insights. Mol Nutr Food Res. 2021;65(1):2000994. doi:10.1002/MNFR.202000994
Chacko BK, Kramer PA, Ravi S, et al. The bioenergetic health index: A new concept in mitochondrial translational research. Clin Sci. 2014;127(6):367-373. doi:10.1042/CS20140101
Yue L, Yao H. Mitochondrial dysfunction in inflammatory responses and cellular senescence: pathogenesis and pharmacological targets for chronic lung diseases. Br J Pharmacol. 2016;173(15):2305-2318. doi:10.1111/BPH.13518
Mahadevan G, Valiyaveettil S. Understanding the interactions of poly(methyl methacrylate) and poly(vinyl chloride) nanoparticles with BHK-21 cell line. Sci Rep. 2021;11(1):1-15. doi:10.1038/s41598-020-80708-0
Jennemann R, Rabionet M, Gorgas K, et al. Loss of ceramide synthase 3 causes lethal skin barrier disruption. Hum Mol Genet. 2012;21(3):586-608. doi:10.1093/HMG/DDR494
Baroni A, Buommino E, De Gregorio V, Ruocco E, Ruocco V, Wolf R. Structure and function of the epidermis related to barrier properties. Clin Dermatol. 2012;30(3):257-262. doi:10.1016/J.CLINDERMATOL.2011.08.007
Chen L, Deng H, Cui H, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018;9(6):7204-7218. doi:10.18632/ONCOTARGET.23208
Lee BM, Park SJ, Noh I, Kim CH. The effects of the molecular weights of hyaluronic acid on the immune responses. Biomater Res. 2021;25(1):1-13. doi:10.1186/S40824-021-00228-4/FIGURES/7
McGarry N, Murray CL, Garvey S, et al. Double stranded RNA drives anti-viral innate immune responses, sickness behavior and cognitive dysfunction dependent on DsRNA length, IFNAR1 expression and age. Brain Behav Immun. 2021;95:413-428. doi:10.1016/J.BBI.2021.04.016
Mueller FS, Richetto J, Hayes LN, et al. Influence of poly(I:C) variability on thermoregulation, immune responses and pregnancy outcomes in mouse models of maternal immune activation. Brain Behav Immun. 2019;80:406-418. doi:10.1016/J.BBI.2019.04.019
Ansel J, Perry P, Brown J, et al. Cytokine modulation of keratinocyte cytokines. J Invest Dermatol. 1990;94(6 Suppl):s101-s107. doi:10.1111/1523-1747.EP12876053
Oo YH, Shetty S, Adams DH. Immunology and liver disease the role of chemokines in the recruitment of lymphocytes to the liver. Dig Dis. 2010;28(1):31-44. doi:10.1159/000282062
Marques RE, Guabiraba R, Russo RC, Teixeira MM. Targeting CCL5 in inflammation. Expert Opin Ther Targets. 2013;17(12):1439-1460. doi:10.1517/14728222.2013.837886
Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118(11):3546-3556. doi:10.1172/JCI36130
Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20(23):6008. doi:10.3390/IJMS20236008
Gelb H, Schumacher HR, Cuckler J, Baker DG. In vivo inflammatory response to polymethylmethacrylate particulate debris: effect of size, morphology, and surface area. J Orthop Res. 1994;8(1):83-92. doi:10.1002/jor.1100120111
Thomson LA, Law FC, James KH, Rushton N. Biocompatibility of particulate polymethylmethacrylate bone cements: A comparative study in vitro and in vivo. Biomaterials. 1992;13(12):811-818. doi:10.1016/0142-9612(92)90173-l
Evans SJ, Clift MJD, Singh N, et al. In vitro detection of in vitro secondary mechanisms of genotoxicity induced by engineered nanomaterials. Part Fibre Toxicol. 2019;16(1):1-14. doi:10.1186/S12989-019-0291-7/FIGURES/6
Awan T, Babendreyer A, Wozniak J, et al. Expression of the metalloproteinase ADAM8 is upregulated in liver inflammation models and enhances cytokine release In vitro. Mediat Inflamm. 2021;2021:1-15. doi:10.1155/2021/6665028
Wang J, Xu S, Lv W, et al. Uridine phosphorylase 1 is a novel immune-related target and predicts worse survival in brain glioma. Cancer Med. 2020;9(16):5940-5947. doi:10.1002/CAM4.3251
Ryniawec JM, Coope MR, Loertscher E, et al. GLUT3/SLC2A3 is an endogenous marker of hypoxia in prostate cancer cell lines and patient-derived xenograft tumors. Diagnostics. 2022;12(3):676. doi:10.3390/DIAGNOSTICS12030676/S1
Ziegler GC, Almos P, McNeill RV, Jansch C, Lesch KP. Cellular effects and clinical implications of SLC2A3 copy number variation. J Cell Physiol. 2020;235(12):9021-9036. doi:10.1002/JCP.29753
Gao H, Liang J, Duan J, et al. A prognosis marker SLC2A3 correlates with EMT and immune signature in colorectal cancer. Front Oncol. 2021;11:638099. doi:10.3389/fonc.2021.638099
Yao X, He Z, Qin C, et al. SLC2A3 promotes macrophage infiltration by glycolysis reprogramming in gastric cancer. Cancer Cell Int. 2020;20(1):503. doi:10.1186/S12935-020-01599-9
Zhang Y, Tian Z, Gerard D, et al. Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated. Sci Rep. 2021;11(1):1804. doi:10.1038/S41598-021-81495-Y
Biddlestone J, Bandarra D, Rocha S. The role of hypoxia in inflammatory disease (Review). Int J Mol Med. 2015;35(4):859-869. doi:10.3892/IJMM.2015.2079/HTML
Fuhrmann DC, Brüne B. Mitochondrial composition and function under the control of hypoxia. Redox Biol. 2017;12:208-215. doi:10.1016/J.REDOX.2017.02.012
Di Ianni E, Møller P, Vogel UB, Jacobsen NR. Pro-inflammatory response and genotoxicity caused by clay and graphene nanomaterials in A549 and THP-1 cells. Mutat Res Toxicol Environ Mutagen. 2021;872:503405. doi:10.1016/J.MRGENTOX.2021.503405
Ray PD, Huang B-W, Tsuji Y. Reactive Oxygen Species (ROS) Homeostasis and Redox Regulation in Cellular Signaling. 2012. doi:10.1016/j.cellsig.2012.01.008
Food and Drug Administration. Conveying Materials Information about Medical Devices to Patients and Healthcare Providers: Considerations for a Framework. 2021.
Ahmad Z, Al-Awadi NA, Al-Sagheer F. Thermal degradation studies in poly(vinyl chloride)/poly(methyl methacrylate) blends. Polym Degrad Stab. 2008;93(2):456-465. doi:10.1016/J.POLYMDEGRADSTAB.2007.11.019
Abouelezz M, Waters PF. Studies on the Photodegradation of Poly(Methyl Methacrylate); Washington DC. 1978. doi:10.6028/NBS.IR.78-1463
Michel RE, Chapman FW, Mao TJ. Electron spin resonance studies of photodegradation in poly(methylmethacrylate) electron spin resonance studies of photo degradation in poly(methylmethacrylate). Cit J Chem Phys. 1966;45:15-4611. doi:10.1063/1.1727543
Speight JG. Monomers, polymers, and plastics. Handbook of Industrial Hydrocarbon Processes. Gulf Professional Publishing; 2019:597-649. doi:10.1016/b978-0-12-809923-0.00014-x
Wochnowski C, Eldin MAS, Metev S. UV-laser-assisted degradation of poly(methyl methacrylate). Polym Degrad Stab. 2005;89(2):252-264. doi:10.1016/J.POLYMDEGRADSTAB.2004.11.024
Danilewicz-Stysiak Z. Experimental investigations on the cytotoxic nature of methyl methacrylate. J Prosthet Dent. 1980;44(1):13-16. doi:10.1016/0022-3913(80)90038-4
Ansteinsson V, Kopperud HB, Morisbak E, Samuelsen JT. Cell toxicity of methacrylate monomers-the role of glutathione adduct formation. J Biomed Mater Res A. 2013;101(12):3504-3510. doi:10.1002/JBM.A.34652
Teo AJT, Mishra A, Park I, Kim YJ, Park WT, Yoon YJ. Polymeric biomaterials for medical implants and devices. ACS Biomater Sci Eng. 2016;2(4):454-472. doi:10.1021/acsbiomaterials.5b00429
Jiao Y, Ma S, Li J, et al. The influences of N-acetyl cysteine (NAC) on the cytotoxicity and mechanical properties of poly-methylmethacrylate (PMMA)-based dental resin. PeerJ. 2015;2015(3):1-16. doi:10.7717/PEERJ.868
International Organization for Standardization. ISO 10993-12: Biological Evaluation of Medical Devices-Part 12: Sample Preparation and Reference Materials; Switzerland. 2012.
Hamajima K, Ozawa R, Saruta J, et al. The effect of TBB, as an initiator, on the biological compatibility of PMMA/MMA bone cement. Int J Mol Sci. 2020;21(11):4016. doi:10.3390/IJMS21114016