Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells
<p>Cell viability of gingival fibroblasts and HSC2. Cells were exposed overnight to the serum-free media with a serial dilution of DMF and formazan formation is normalized to untreated control cells. Representative live/dead staining of gingival fibroblasts allows to distinguish green living from red dead cells. Cells were grown with and without DMF in the presence of IL1β and TNFα overnight and subjected to live/dead staining. The scale bar represents 170 μm.</p> "> Figure 2
<p>Gene expression of chemokines in gingival fibroblasts exposed to IL1β and TNFα. A total of 100 μM DMF significantly reduced chemokine expression. Data are expressed as x-fold over the respective untreated controls. Data points represent six and four independent experiments for PCR and ELISA, respectively. Statistical analysis was based on ratio-paired <span class="html-italic">t</span>-tests, and <span class="html-italic">p</span>-values are indicated.</p> "> Figure 3
<p>Gene expression of chemokine in gingival fibroblasts under saliva (SLV). A total of 100 μM DMF significantly reduced chemokine expression. Data are expressed as x-fold over the respective untreated controls. Data points represent six and four independent experiments for PCR and ELISA, respectively. Statistical analysis was based on ratio-paired <span class="html-italic">t</span>-tests, and <span class="html-italic">p</span>-values are indicated.</p> "> Figure 4
<p>Gene expression of chemokine in HSC2 cells under IL1β and TNFα. A total of 100 μM DMF significantly reduced chemokine expression. Data are expressed as x-fold over the respective untreated controls. Data points represent six and four independent experiments for PCR and ELISA, respectively. Statistical analysis was based on ratio-paired <span class="html-italic">t</span>-tests, and <span class="html-italic">p</span>-values are indicated.</p> "> Figure 5
<p>Effects of DMF on phosphorylation of signaling molecules in IL1β and TNFα-stimulated gingival fibroblasts. The cell lysates were used for the detection of phosphorylated or total extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and p65 via Western blotting.</p> "> Figure 6
<p>Rheological properties of the hydrogels. Temperature-sweep measurements of the hydrogels with different components. 0.5%GG: 5 mg/mL gellan gum hydrogel, 0.75%GG: 7.5 mg/mL gellan gam hydrogel, 1.25%GG: 12.5 mg/mL gellan gum hydrogel, 1%GG: 10 mg/mL gellan gum hydrogel, LG: 10 mg/mL gellan gum hydrogel with 0.5 mM DMF, HG: 10 mg/mL gellan gum hydrogel with 1 mM DMF.</p> "> Figure 7
<p>(<b>A</b>) Representative SEM images of the gellan gum hydrogels with and without DMF; (<b>B</b>) injectability of the hydrogels; (<b>C</b>) swelling and degradation properties of the hydrogel. GG: gellan gum hydrogel alone; LG: gellan gum hydrogel with 0.5 mM DMF, HG: gellan gum hydrogel with 1 mM DMF.</p> "> Figure 8
<p>The release profile of the DMF-loaded hydrogels. Long-term slow-release kinetics of DMF from the gellan gum hydrogel in both LG and HG groups. LG: gellan gum hydrogel with 2.5 mM DMF, HG: gellan gum hydrogel with 5 mM DMF.</p> "> Figure 9
<p>(<b>A</b>) Schematic diagram of gingival fibroblast cocultured with hydrogel; (<b>B</b>) representative images of live/dead staining of gingival fibroblasts with hydrogels. Cells were grown with DMF-loaded hydrogels overnight and subjected to live/dead staining. WO: without treatment; GG: gellan gum hydrogel alone; LG: gellan gum hydrogel with 0.5 mM DMF, HG: gellan gum hydrogel with 1 mM DMF. Scale bars represent 170 μm.</p> "> Figure 10
<p>Gene expression of chemokines in gingival fibroblasts under IL1β and TNFα. HG and LG significantly reduced chemokine expression. Data are expressed as x-fold over the respective untreated controls. Data points represent four independent experiments for PCR and ELISA. Statistical analysis was based on ratio-paired <span class="html-italic">t</span>-tests and <span class="html-italic">p</span>-values are indicated.</p> ">
Abstract
:1. Introduction
2. Results
2.1. Screening of DMF Concentrations
2.2. DMF Reduced IL1β and TNFα or SLV-Induced Chemokines in Gingival Fibroblasts
2.3. DMF Reduced IL1β and TNFα-Induced Chemokines in HSC2 Cells
2.4. DMF Inhibits the Phosphorylation of ERK and JNK, but Not of p38 or p65, in IL1β and TNFα-Induced Gingival Fibroblasts
2.5. Rheological Properties of Gellan Gum Hydrogel Loaded with DMF
2.6. Morphology, Injectability and Swelling Properties of Gellan Gum Hydrogel Loaded with DMF
2.7. DMF Release
2.8. DMF Released from Hydrogel Reduced IL1β and TNFα-Induced Chemokines in Gingival Fibroblasts
3. Discussion
4. Materials and Methods
4.1. Gingival Fibroblasts and Oral Squamous Cell Carcinoma Cells HSC2
4.2. Dimethyl Fumarate and Inflammatory Agonist Stimulations
4.3. Dimethyl Fumarate-Loaded Gellan Gum Hydrogel
4.4. Physicochemical Properties of Gellan Gum Hydrogel
4.5. Release Kinetics of Dimethyl Fumarate from Gellan Gum Hydrogel
4.6. Cell Viability Assay
4.7. Trypan Blue Staining and Live/Dead Staining
4.8. Real-Time Polymerase Chain Reaction (RT-PCR) and Immunoassay
4.9. Immunofluorescence Analysis
4.10. Western Blot
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Kinane, D.F.; Stathopoulou, P.G.; Papapanou, P.N. Periodontal diseases. Nat. Rev. Dis. Primers 2017, 3, 17038. [Google Scholar] [CrossRef] [PubMed]
- Gruber, R. Osteoimmunology: Inflammatory osteolysis and regeneration of the alveolar bone. J. Clin. Periodontol. 2019, 46 (Suppl. S21), 52–69. [Google Scholar] [CrossRef]
- Bosshardt, D.D. The periodontal pocket: Pathogenesis, histopathology and consequences. Periodontology 2000 2018, 76, 43–50. [Google Scholar] [CrossRef] [PubMed]
- Salvi, G.E.; Aglietta, M.; Eick, S.; Sculean, A.; Lang, N.P.; Ramseier, C.A. Reversibility of experimental peri-implant mucositis compared with experimental gingivitis in humans. Clin. Oral Implants Res. 2012, 23, 182–190. [Google Scholar] [CrossRef] [PubMed]
- Jakubovics, N.S.; Goodman, S.D.; Mashburn-Warren, L.; Stafford, G.P.; Cieplik, F. The dental plaque biofilm matrix. Periodontology 2000 2021, 86, 32–56. [Google Scholar] [CrossRef]
- Renvert, S.; Roos-Jansaker, A.M.; Claffey, N. Non-surgical treatment of peri-implant mucositis and peri-implantitis: A literature review. J. Clin. Periodontol. 2008, 35, 305–315. [Google Scholar] [CrossRef]
- Heitz-Mayfield, L.J.; Trombelli, L.; Heitz, F.; Needleman, I.; Moles, D. A systematic review of the effect of surgical debridement vs non-surgical debridement for the treatment of chronic periodontitis. J. Clin. Periodontol. 2002, 29 (Suppl. S3), 92–102. [Google Scholar] [CrossRef]
- Williams, D.W.; Greenwell-Wild, T.; Brenchley, L.; Dutzan, N.; Overmiller, A.; Sawaya, A.P.; Webb, S.; Martin, D.; Genomics, N.N.; Computational Biology, C.; et al. Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity. Cell 2021, 184, 4090–4104.e15. [Google Scholar] [CrossRef]
- Mo, J.J.; Lai, Y.R.; Huang, Q.R.; Li, Y.R.; Zhang, Y.J.; Chen, R.Y.; Qian, S.J. Single-cell sequencing identifies inflammation-promoting fibroblast-neutrophil interaction in peri-implantitis. J. Clin. Periodontol. 2024, 51, 196–208. [Google Scholar] [CrossRef]
- Majkutewicz, I. Dimethyl fumarate: A review of preclinical efficacy in models of neurodegenerative diseases. Eur. J. Pharmacol. 2022, 926, 175025. [Google Scholar] [CrossRef]
- Venci, J.V.; Gandhi, M.A. Dimethyl fumarate (Tecfidera): A new oral agent for multiple sclerosis. Ann. Pharmacother. 2013, 47, 1697–1702. [Google Scholar] [CrossRef] [PubMed]
- Mrowietz, U.; Barker, J.; Boehncke, W.H.; Iversen, L.; Kirby, B.; Naldi, L.; Reich, K.; Tanew, A.; van de Kerkhof, P.C.M.; Warren, R.B. Clinical use of dimethyl fumarate in moderate-to-severe plaque-type psoriasis: A European expert consensus. J. Eur. Acad. Dermatol. Venereol. 2018, 32 (Suppl. S3), 3–14. [Google Scholar] [CrossRef] [PubMed]
- Bresciani, G.; Manai, F.; Davinelli, S.; Tucci, P.; Saso, L.; Amadio, M. Novel potential pharmacological applications of dimethyl fumarate-an overview and update. Front. Pharmacol. 2023, 14, 1264842. [Google Scholar] [CrossRef] [PubMed]
- Seidel, P.; Merfort, I.; Tamm, M.; Roth, M. Inhibition of NF-kappaB and AP-1 by dimethylfumarate correlates with down-regulated IL-6 secretion and proliferation in human lung fibroblasts. Swiss Med. Wkly. 2010, 140, w13132. [Google Scholar] [CrossRef]
- Seidel, P.; Merfort, I.; Hughes, J.M.; Oliver, B.G.; Tamm, M.; Roth, M. Dimethylfumarate inhibits NF-kappaB function at multiple levels to limit airway smooth muscle cell cytokine secretion. Am. J. Physiol. Lung Cell. Mol. Physiol. 2009, 297, L326–L339. [Google Scholar] [CrossRef] [PubMed]
- Grzegorzewska, A.P.; Seta, F.; Han, R.; Czajka, C.A.; Makino, K.; Stawski, L.; Isenberg, J.S.; Browning, J.L.; Trojanowska, M. Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways. Sci. Rep. 2017, 7, 41605. [Google Scholar] [CrossRef]
- Vandermeeren, M.; Janssens, S.; Borgers, M.; Geysen, J. Dimethylfumarate is an inhibitor of cytokine-induced E-selectin, VCAM-1, and ICAM-1 expression in human endothelial cells. Biochem. Biophys. Res. Commun. 1997, 234, 19–23. [Google Scholar] [CrossRef]
- Laselva, O.; Allegretta, C.; Di Gioia, S.; Avolio, C.; Conese, M. Anti-Inflammatory and Anti-Oxidant Effect of Dimethyl Fumarate in Cystic Fibrosis Bronchial Epithelial Cells. Cells 2021, 10, 2132. [Google Scholar] [CrossRef]
- Li, Y.; Tang, J.; Hu, Y. Dimethyl fumarate protection against collagen II degradation. Biochem. Biophys. Res. Commun. 2014, 454, 257–261. [Google Scholar] [CrossRef]
- McGuire, V.A.; Ruiz-Zorrilla Diez, T.; Emmerich, C.H.; Strickson, S.; Ritorto, M.S.; Sutavani, R.V.; Weibeta, A.; Houslay, K.F.; Knebel, A.; Meakin, P.J.; et al. Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation. Sci. Rep. 2016, 6, 31159. [Google Scholar] [CrossRef]
- Wilms, H.; Sievers, J.; Rickert, U.; Rostami-Yazdi, M.; Mrowietz, U.; Lucius, R. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in-vitro model of brain inflammation. J. Neuroinflamm. 2010, 7, 30. [Google Scholar] [CrossRef]
- Gu, F.; Wu, H.; Huang, Z.; Wang, F.; Yang, R.; Bian, Z.; He, M. The effects of dimethyl fumarate on cytoplasmic LPS-induced noncanonical pyroptosis in periodontal ligament fibroblasts and dental pulp cells. Int. Endod. J. 2023, 56, 869–880. [Google Scholar] [CrossRef] [PubMed]
- Basilotta, R.; Lanza, M.; Filippone, A.; Casili, G.; Mannino, D.; De Gaetano, F.; Chisari, G.; Colarossi, L.; Motta, G.; Campolo, M.; et al. Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial-Mesenchymal Transition. Int. J. Mol. Sci. 2023, 24, 2777. [Google Scholar] [CrossRef] [PubMed]
- Osmalek, T.; Froelich, A.; Tasarek, S. Application of gellan gum in pharmacy and medicine. Int. J. Pharm. 2014, 466, 328–340. [Google Scholar] [CrossRef]
- Lalebeigi, F.; Alimohamadi, A.; Afarin, S.; Aliabadi, H.A.M.; Mahdavi, M.; Farahbakhshpour, F.; Hashemiaval, N.; Khandani, K.K.; Eivazzadeh-Keihan, R.; Maleki, A. Recent advances on biomedical applications of gellan gum: A review. Carbohydr. Polym. 2024, 334, 122008. [Google Scholar] [CrossRef] [PubMed]
- Alharbi, H.Y.; Alnoman, R.B.; Aljohani, M.S.; Al-Anazia, M.; Monier, M. Synthesis and characterization of gellan gum-based hydrogels for drug delivery applications. Int. J. Biol. Macromol. 2024, 258, 128828. [Google Scholar] [CrossRef]
- Villarreal-Otalvaro, C.; Coburn, J.M. Fabrication Methods and Form Factors of Gellan Gum-Based Materials for Drug Delivery and Anti-Cancer Applications. ACS Biomater. Sci. Eng. 2023, 9, 3832–3842. [Google Scholar] [CrossRef]
- Giavasis, I.; Harvey, L.M.; McNeil, B. Gellan gum. Crit. Rev. Biotechnol. 2000, 20, 177–211. [Google Scholar] [CrossRef]
- Mousavi, S.S.; Keshvari, H.; Daemi, H. Partial sulfation of gellan gum produces cytocompatible, body temperature-responsive hydrogels. Int. J. Biol. Macromol. 2023, 235, 123525. [Google Scholar] [CrossRef]
- Garcia, M.T.; Carmo, P.; Figueiredo-Godoi, L.M.A.; Goncalves, N.I.; Lima, P.M.N.; Ramos, L.P.; Oliveira, L.D.; Borges, A.L.S.; Shukla, A.; Junqueira, J.C. Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections. Pharmaceutics 2024, 16, 298. [Google Scholar] [CrossRef]
- Choi, J.H.; Park, A.; Lee, W.; Youn, J.; Rim, M.A.; Kim, W.; Kim, N.; Song, J.E.; Khang, G. Preparation and characterization of an injectable dexamethasone-cyclodextrin complexes-loaded gellan gum hydrogel for cartilage tissue engineering. J. Control. Release 2020, 327, 747–765. [Google Scholar] [CrossRef] [PubMed]
- Musazzi, U.M.; Cencetti, C.; Franze, S.; Zoratto, N.; Di Meo, C.; Procacci, P.; Matricardi, P.; Cilurzo, F. Gellan Nanohydrogels: Novel Nanodelivery Systems for Cutaneous Administration of Piroxicam. Mol. Pharm. 2018, 15, 1028–1036. [Google Scholar] [CrossRef]
- Osmalek, T.; Froelich, A.; Milanowski, B.; Bialas, M.; Hyla, K.; Szybowicz, M. pH-Dependent Behavior of Novel Gellan Beads Loaded with Naproxen. Curr. Drug Deliv. 2018, 15, 52–63. [Google Scholar] [CrossRef] [PubMed]
- Mahdi, M.H.; Conway, B.R.; Mills, T.; Smith, A.M. Gellan gum fluid gels for topical administration of diclofenac. Int. J. Pharm. 2016, 515, 535–542. [Google Scholar] [CrossRef] [PubMed]
- Santos, A.F.P.; Cervantes, L.C.C.; Panahipour, L.; Souza, F.A.; Gruber, R. Proof-of-Principle Study Suggesting Potential Anti-Inflammatory Activity of Butyrate and Propionate in Periodontal Cells. Int. J. Mol. Sci. 2022, 23, 11006. [Google Scholar] [CrossRef]
- Cvikl, B.; Lussi, A.; Moritz, A.; Sculean, A.; Gruber, R. Sterile-filtered saliva is a strong inducer of IL-6 and IL-8 in oral fibroblasts. Clin. Oral Investig. 2015, 19, 385–399. [Google Scholar] [CrossRef]
- Panahipour, L.; Botta, S.; Abbasabadi, A.O.; Afradi, Z.; Gruber, R. Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells. Int. J. Mol. Sci. 2023, 24, 13991. [Google Scholar] [CrossRef] [PubMed]
- Vanoli, V.; Delleani, S.; Casalegno, M.; Pizzetti, F.; Makvandi, P.; Haugen, H.; Mele, A.; Rossi, F.; Castiglione, F. Hyaluronic acid-based hydrogels: Drug diffusion investigated by HR-MAS NMR and release kinetics. Carbohydr. Polym. 2023, 301, 120309. [Google Scholar] [CrossRef]
- Maderuelo, C.; Zarzuelo, A.; Lanao, J.M. Critical factors in the release of drugs from sustained release hydrophilic matrices. J. Control. Release 2011, 154, 2–19. [Google Scholar] [CrossRef]
- Ameen, D.; Michniak-Kohn, B. Transdermal delivery of dimethyl fumarate for Alzheimer’s disease: Effect of penetration enhancers. Int. J. Pharm. 2017, 529, 465–473. [Google Scholar] [CrossRef]
- Litjens, N.H.; van Strijen, E.; van Gulpen, C.; Mattie, H.; van Dissel, J.T.; Thio, H.B.; Nibbering, P.H. In vitro pharmacokinetics of anti-psoriatic fumaric acid esters. BMC Pharmacol. 2004, 4, 22. [Google Scholar] [CrossRef] [PubMed]
- Moutsopoulos, N.M.; Moutsopoulos, H.M. The oral mucosa: A barrier site participating in tissue-specific and systemic immunity. Oral Dis. 2018, 24, 22–25. [Google Scholar] [CrossRef] [PubMed]
- Dutzan, N.; Abusleme, L.; Bridgeman, H.; Greenwell-Wild, T.; Zangerle-Murray, T.; Fife, M.E.; Bouladoux, N.; Linley, H.; Brenchley, L.; Wemyss, K.; et al. On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity 2017, 46, 133–147. [Google Scholar] [CrossRef]
- Kim, T.S.; Ikeuchi, T.; Theofilou, V.I.; Williams, D.W.; Greenwell-Wild, T.; June, A.; Adade, E.E.; Li, L.; Abusleme, L.; Dutzan, N.; et al. Epithelial-derived interleukin-23 promotes oral mucosal immunopathology. Immunity 2024, 57, 859–875.e811. [Google Scholar] [CrossRef] [PubMed]
- Zhu, H.; Chen, G.; Wang, Y.; Lin, X.; Zhou, J.; Wang, Z.; Suo, N. Dimethyl fumarate protects nucleus pulposus cells from inflammation and oxidative stress and delays the intervertebral disc degeneration. Exp. Ther. Med. 2020, 20, 269. [Google Scholar] [CrossRef]
- Zinger, N.; Ponath, G.; Sweeney, E.; Nguyen, T.D.; Lo, C.H.; Diaz, I.; Dimov, A.; Teng, L.; Zexter, L.; Comunale, J.; et al. Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions. Neurol. Neuroimmunol. Neuroinflamm. 2022, 9, e1138. [Google Scholar] [CrossRef]
- Pakulska, M.M.; Vulic, K.; Tam, R.Y.; Shoichet, M.S. Hybrid Crosslinked Methylcellulose Hydrogel: A Predictable and Tunable Platform for Local Drug Delivery. Adv. Mater. 2015, 27, 5002–5008. [Google Scholar] [CrossRef]
- Holloway, J.L.; Ma, H.; Rai, R.; Burdick, J.A. Modulating hydrogel crosslink density and degradation to control bone morphogenetic protein delivery and in vivo bone formation. J. Control. Release 2014, 191, 63–70. [Google Scholar] [CrossRef]
- Mehdi-Alamdarlou, S.; Ahmadi, F.; Azadi, A.; Shahbazi, M.A.; Heidari, R.; Ashrafi, H. A cell-mimicking platelet-based drug delivery system as a potential carrier of dimethyl fumarate for multiple sclerosis. Int. J. Pharm. 2022, 625, 122084. [Google Scholar] [CrossRef]
- Sinha, S.; Garg, V.; Sonali; Singh, R.P.; Dutt, R. Chitosan-alginate core-shell-corona shaped nanoparticles of dimethyl fumarate in orodispersible film to improve bioavailability in treatment of multiple sclerosis: Preparation, characterization and biodistribution in rats. J. Drug Deliv. Sci. Technol. 2021, 64, 102645. [Google Scholar] [CrossRef]
- Subhash, S.; Chaurawal, N.; Raza, K. Promises of Lipid-Based Nanocarriers for Delivery of Dimethyl Fumarate to Multiple Sclerosis Brain. Methods Mol. Biol. 2024, 2761, 457–475. [Google Scholar] [CrossRef] [PubMed]
- Ferrara, F.; Benedusi, M.; Cervellati, F.; Sguizzato, M.; Montesi, L.; Bondi, A.; Drechsler, M.; Pula, W.; Valacchi, G.; Esposito, E. Dimethyl Fumarate-Loaded Transethosomes: A Formulative Study and Preliminary Ex Vivo and In Vivo Evaluation. Int. J. Mol. Sci. 2022, 23, 8756. [Google Scholar] [CrossRef] [PubMed]
- Horimoto, K.; Suyama, Y.; Sasaki, T.; Fukui, K.; Feng, L.; Sun, M.; Tang, Y.; Zhang, Y.; Chen, D.; Han, F. Phosphorylated protein chip combined with artificial intelligence tools for precise drug screening. J. Biomed. Res. 2024, 38, 195–205. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Li, A.; Zhang, D.; Zhang, M.; Ma, L.; Li, Y.; Wang, W.; Nan, K.; Chen, H.; Li, L. Injectable double-network hydrogel for corneal repair. Chem. Eng. J. 2023, 455, 140698. [Google Scholar] [CrossRef]
Genes | Forward Sequences | Afterward Sequences |
---|---|---|
CXCL1 | TCCTGCATCCCCCATAGTTA | CTTCAGGAACAGCCACCAGT |
CXCL2 | CCCATGGTTAAGAAAATCATCG | CTTCAGGAACAGCCACCAAT |
CXCL8 | AACTTCTCCACAACCCTCTG | TTGGCAGCCTTCCTGATTTC |
CXCL10 | TGCCATTCTGATTTGCTGCC | TGCAGGTACAGCGTACAGTT |
CCL2 | AGAATCACCAGCAGCAAGTGTC | TCCTGAACCCACTTCTGCTTG |
GAPDH | AAGCCACATCGCTCAGACAC | GCCCAATACGACCAAATCC |
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Wang, L.; dos Santos Sanches, N.; Panahipour, L.; Imani, A.; Yao, Y.; Zhang, Y.; Li, L.; Gruber, R. Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells. Int. J. Mol. Sci. 2024, 25, 9485. https://doi.org/10.3390/ijms25179485
Wang L, dos Santos Sanches N, Panahipour L, Imani A, Yao Y, Zhang Y, Li L, Gruber R. Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells. International Journal of Molecular Sciences. 2024; 25(17):9485. https://doi.org/10.3390/ijms25179485
Chicago/Turabian StyleWang, Lei, Natalia dos Santos Sanches, Layla Panahipour, Atefe Imani, Yili Yao, Yan Zhang, Lingli Li, and Reinhard Gruber. 2024. "Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells" International Journal of Molecular Sciences 25, no. 17: 9485. https://doi.org/10.3390/ijms25179485
APA StyleWang, L., dos Santos Sanches, N., Panahipour, L., Imani, A., Yao, Y., Zhang, Y., Li, L., & Gruber, R. (2024). Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells. International Journal of Molecular Sciences, 25(17), 9485. https://doi.org/10.3390/ijms25179485