Effect of orodispersible hyaluronic acid film on palatal mucosa wound healing
Jeong Hyun Lee
Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
Contribution: Data curation, Formal analysis, Writing - original draft
Search for more papers by this authorKo Eun Lee
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Contribution: Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorSang Wook Kang
Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul, South Korea
Contribution: Data curation, Formal analysis
Search for more papers by this authorSeung Hwan Park
Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
Contribution: Data curation, Formal analysis
Search for more papers by this authorYong Kwon Chae
Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Contribution: Writing - original draft
Search for more papers by this authorMyoung-Han Lee
Jinwoo Bio Co. Ltd., Yongin-si, South Korea
Contribution: Data curation, Formal analysis, Resources
Search for more papers by this authorDong-Keun Kweon
Jinwoo Bio Co. Ltd., Yongin-si, South Korea
Contribution: Data curation, Formal analysis, Resources
Search for more papers by this authorSung Chul Choi
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, South Korea
Contribution: Validation
Search for more papers by this authorCorresponding Author
Ok Hyung Nam
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, South Korea
Correspondence
Ok Hyung Nam, Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Kyungheedae-Ro 26, Dongdaemoon-Gu, Seoul 02447, South Korea.
Email: [email protected]
Contribution: Conceptualization, Data curation, Validation, Formal analysis, Funding acquisition, Writing - original draft, Writing - review & editing
Search for more papers by this authorJeong Hyun Lee
Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
Contribution: Data curation, Formal analysis, Writing - original draft
Search for more papers by this authorKo Eun Lee
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Contribution: Validation, Writing - original draft, Writing - review & editing
Search for more papers by this authorSang Wook Kang
Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul, South Korea
Contribution: Data curation, Formal analysis
Search for more papers by this authorSeung Hwan Park
Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
Contribution: Data curation, Formal analysis
Search for more papers by this authorYong Kwon Chae
Department of Dentistry, Graduate School, Kyung Hee University, Seoul, South Korea
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Contribution: Writing - original draft
Search for more papers by this authorMyoung-Han Lee
Jinwoo Bio Co. Ltd., Yongin-si, South Korea
Contribution: Data curation, Formal analysis, Resources
Search for more papers by this authorDong-Keun Kweon
Jinwoo Bio Co. Ltd., Yongin-si, South Korea
Contribution: Data curation, Formal analysis, Resources
Search for more papers by this authorSung Chul Choi
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, South Korea
Contribution: Validation
Search for more papers by this authorCorresponding Author
Ok Hyung Nam
Department of Pediatric Dentistry, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul, South Korea
Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Seoul, South Korea
Correspondence
Ok Hyung Nam, Department of Pediatric Dentistry, School of Dentistry, Kyung Hee University, Kyungheedae-Ro 26, Dongdaemoon-Gu, Seoul 02447, South Korea.
Email: [email protected]
Contribution: Conceptualization, Data curation, Validation, Formal analysis, Funding acquisition, Writing - original draft, Writing - review & editing
Search for more papers by this authorJeong Hyun Lee and Ko Eun Lee contributed equally to this work as first authors.
Abstract
Objective
The objective of the study was to evaluate the healing effect of hyaluronic acid films on palatal wounds.
Materials and Methods
After making 5-mm diameter palatal wounds, 72 rats were randomly assigned to three groups: control, hyaluronic acid gel, and hyaluronic acid film. The animals were sacrificed at 3, 7, and 21 days after the experiment. Clinical, histological, and RT-PCR analyses were performed. Human ex vivo oral mucosa models were used. Histological analysis and pan-cytokeratin staining were performed at 5 days after wound creation.
Results
In rat model, both gels and films showed favorable healing on Days 3 and 7 compared with healing in the control (p < 0.05). Film showed remarkable VEGF and α-SMA expression than did the others (p < 0.05). Immunohistochemical analysis showed that film exhibited significantly lower CD68 and greater α-SMA and vimentin expression levels than those in the others (p < 0.05). In human model, re-epithelialization rate of film group was significantly higher than that of the others. Complete epithelial regeneration was confirmed only in film group using pan-cytokeratin staining.
Conclusions
Within the limits of this study, hyaluronic acid film outperformed gels in terms of palatal wound healing in both models.
CONFLICT OF INTEREST STATEMENT
The authors report that there are no direct or indirect conflicts of interest involving associations with commercial entities that supported the work reported in the submitted manuscript, associations with commercial entities that might have an interest in the submitted manuscript, financial associations involving family members and other relevant non-financial associations.
Open Research
DATA AVAILABILITY STATEMENT
Datasets related to this article will be available upon request to the corresponding author.
REFERENCES
- Agarwal, C., Tarun Kumar, A. B., & Mehta, D. S. (2015). Comparative evaluation of free gingival graft and AlloDerm(®) in enhancing the width of attached gingival: A clinical study. Contemporary Clinical Dentistry, 6(4), 483–488. https://doi.org/10.4103/0976-237x.169838
- Asparuhova, M. B., Kiryak, D., Eliezer, M., Mihov, D., & Sculean, A. (2019). Activity of two hyaluronan preparations on primary human oral fibroblasts. Journal of Periodontal Research, 54(1), 33–45. https://doi.org/10.1111/jre.12602
- Bao, P., Kodra, A., Tomic-Canic, M., Golinko, M. S., Ehrlich, H. P., & Brem, H. (2009). The role of vascular endothelial growth factor in wound healing. The Journal of Surgical Research, 153(2), 347–358. https://doi.org/10.1016/j.jss.2008.04.023
- Bosco, A. F., & Bosco, J. M. (2007). An alternative technique to the harvesting of a connective tissue graft from a thin palate: Enhanced wound healing. The International Journal of Periodontics & Restorative Dentistry, 27(2), 133–139.
- Chen, W. Y., & Abatangelo, G. (1999). Functions of hyaluronan in wound repair. Wound Repair and Regeneration, 7(2), 79–89. https://doi.org/10.1046/j.1524-475x.1999.00079.x
- Cheng, F., Shen, Y., Mohanasundaram, P., Lindström, M., Ivaska, J., Ny, T., & Eriksson, J. E. (2016). Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-β-slug signaling. Proceedings of the National Academy of Sciences of the United States of America, 113(30), E4320–E4327. https://doi.org/10.1073/pnas.1519197113
- Cho, J. R., Lee, M. H., Oh, H. K., Kim, H., Kweon, D. K., Kang, S. M., Kim, B. K., Heo, C. Y., Kim, D. W., & Kang, S. B. (2021). Efficacy of hyaluronic acid film on perianal wound healing in a rat model. Annals of Surgical Treatment and Research, 101(4), 206–213. https://doi.org/10.4174/astr.2021.101.4.206
- Cho, Y. D., Kim, K. H., Lee, Y. M., Ku, Y., & Seol, Y. J. (2021). Periodontal wound healing and tissue regeneration: A narrative review. Pharmaceuticals (Basel), 14(5), 456. https://doi.org/10.3390/ph14050456
- Del Pizzo, M., Modica, F., Bethaz, N., Priotto, P., & Romagnoli, R. (2002). The connective tissue graft: A comparative clinical evaluation of wound healing at the palatal donor site. A preliminary study. Journal of Clinical Periodontology, 29(9), 848–854. https://doi.org/10.1034/j.1600-051x.2002.290910.x
- Fallacara, A., Baldini, E., Manfredini, S., & Vertuani, S. (2018). Hyaluronic acid in the third millennium. Polymers (Basel), 10(7), 701. https://doi.org/10.3390/polym10070701
- Farsaei, S., Khalili, H., & Farboud, E. S. (2012). Potential role of statins on wound healing: Review of the literature. International Wound Journal, 9(3), 238–247. https://doi.org/10.1111/j.1742-481X.2011.00888.x
- Hämmerle, C. H., & Giannobile, W. V. (2014). Biology of soft tissue wound healing and regeneration--consensus report of group 1 of the 10th European workshop on periodontology. Journal of Clinical Periodontology, 41(Suppl 15), S1–S5. https://doi.org/10.1111/jcpe.12221
- Ke, C., Wang, D., Sun, Y., Qiao, D., Ye, H., & Zeng, X. (2013). Immunostimulatory and antiangiogenic activities of low molecular weight hyaluronic acid. Food and Chemical Toxicology, 58, 401–407. https://doi.org/10.1016/j.fct.2013.05.032
- Keswani, S. G., Balaji, S., Le, L. D., Leung, A., Parvadia, J. K., Frischer, J., Yamano, S., Taichman, N., & Crombleholme, T. M. (2013). Role of salivary vascular endothelial growth factor (VEGF) in palatal mucosal wound healing. Wound Repair and Regeneration, 21(4), 554–562. https://doi.org/10.1111/wrr.12065
- Kull, S., Martinelli, I., Briganti, E., Losi, P., Spiller, D., Tonlorenzi, S., & Soldani, G. (2013). Glubran2 surgical glue: in vitro evaluation of adhesive and mechanical properties. The Journal of Surgical Research, 157(1), e15–e21. https://doi.org/10.1016/j.jss.2009.01.034
- Kweon, D. K., & Park, S. H. (2021). Method for manufacturing hyaluronate fibers by using melt spinning and hyaluronate fibers manufactured thereby. In: Google Patents.
- Landén, N. X., Li, D., & Ståhle, M. (2016). Transition from inflammation to proliferation: A critical step during wound healing. Cellular and Molecular Life Sciences, 73(20), 3861–3885. https://doi.org/10.1007/s00018-016-2268-0
- Lee, J. H., Lee, K. E., Nam, O. H., Chae, Y. K., Lee, M. H., Kweon, D. K., Kim, M. S., Lee, H. S., & Choi, S. C. (2022). Orodispersible hyaluronic acid film delivery for oral wound healing in rats. Journal of Dental Sciences, 17, 1595–1603. https://doi.org/10.1016/j.jds.2022.04.004
- Lee, J. H., Park, S. H., Mohammed, A. N., Lee, M. H., Kweon, D. K., Chae, Y., Lee, K., Kim, M., Lee, H., Choi, S., & Nam, O. H. (2022). Effects of ginsenoside Rb1 loaded films on oral wound healing. Journal Korean Acad Pediatr Dent, 49(3), 300–309. https://doi.org/10.5933/JKAPD.2022.49.3.300
10.5933/JKAPD.2022.49.3.300 Google Scholar
- Lee, O. J., Kim, J. H., Moon, B. M., Chao, J. R., Yoon, J., Ju, H. W., Lee, J. M., Park, H. J., Kim, D. W., Kim, S. J., & Park, H. S. (2016). Fabrication and characterization of hydrocolloid dressing with silk fibroin nanoparticles for wound healing. Tissue Engineering and Regenerative Medicine, 13, 218–226. https://doi.org/10.1007/s13770-016-9058-5
- Litwiniuk, M., Krejner, A., Speyrer, M. S., Gauto, A. R., & Grzela, T. (2016). Hyaluronic acid in inflammation and tissue regeneration. Wounds, 28(3), 78–88.
- Marin, S., Popovic-Pejicic, S., Radosevic-Caric, B., Trtić, N., Tatic, Z., & Selakovic, S. (2020). Hyaluronic acid treatment outcome on the post-extraction wound healing in patients with poorly controlled type 2 diabetes: A randomized controlled split-mouth study. Medicina Oral, Patología Oral y Cirugía Bucal, 25(2), e154–e160. https://doi.org/10.4317/medoral.23061
- Miller, P. D., Jr., & Allen, E. P. (1996). The development of periodontal plastic surgery. Periodontology 2000, 11, 7–17. https://doi.org/10.1111/j.1600-0757.1996.tb00178.x
- National Research Council Committee for the Update of the Guide for the, C., & Use of Laboratory, A. (2011). The national academies collection: Reports funded by National Institutes of Health. In Guide for the care and use of laboratory animals. National Academies Press (US).
10.17226/25801 Google Scholar
- Pastar, I., Stojadinovic, O., Yin, N. C., Ramirez, H., Nusbaum, A. G., Sawaya, A., Patel, S. B., Khalid, L., Isseroff, R. R., & Tomic-Canic, M. (2014). Epithelialization in wound healing: A comprehensive review. Adv Wound Care (New Rochelle), 3(7), 445–464. https://doi.org/10.1089/wound.2013.0473
- Piipponen, M., Li, D., & Landén, N. X. (2020). The immune functions of keratinocytes in skin wound healing. International Journal of Molecular Sciences, 21(22), 8790. https://doi.org/10.3390/ijms21228790
- Rateitschak, K. H., Egli, U., & Fringeli, G. (1979). Recession: A 4-year longitudinal study after free gingival grafts. Journal of Clinical Periodontology, 6(3), 158–164. https://doi.org/10.1111/j.1600-051x.1979.tb02195.x
- Santoro, M. M., & Gaudino, G. (2005). Cellular and molecular facets of keratinocyte reepithelization during wound healing. Experimental Cell Research, 304(1), 274–286. https://doi.org/10.1016/j.yexcr.2004.10.033
- Silva, C. O., Ribeiro Edel, P., Sallum, A. W., & Tatakis, D. N. (2010). Free gingival grafts: Graft shrinkage and donor-site healing in smokers and non-smokers. Journal of Periodontology, 81(5), 692–701. https://doi.org/10.1902/jop.2010.090381
- Simões, D., Miguel, S. P., Ribeiro, M. P., Coutinho, P., Mendonça, A. G., & Correia, I. J. (2018). Recent advances on antimicrobial wound dressing: A review. European Journal of Pharmaceutics and Biopharmaceutics, 127, 130–141. https://doi.org/10.1016/j.ejpb.2018.02.022
- Taskan, M. M., Balci Yuce, H., Karatas, O., Gevrek, F., Isiker Kara, G., Celt, M., & Sirma Taskan, E. (2021). Hyaluronic acid with antioxidants improve wound healing in rats. Biotechnic & Histochemistry, 96(7), 536–545. https://doi.org/10.1080/10520295.2020.1832255
- Walicová, V., & Gajdziok, J. (2016). Oral films as perspective dosage form. Ceská a Slovenská Farmacie, 65(1), 15–21.
- Wilhelm, K. P., Wilhelm, D., & Bielfeldt, S. (2017). Models of wound healing: An emphasis on clinical studies. Skin Research and Technology, 23(1), 3–12. https://doi.org/10.1111/srt.12317
- Wyrębek, B., Górski, B., & Górska, R. (2018). Patient morbidity at the palatal donor site depending on gingival graft dimension. Dental and Medical Problems, 55(2), 153–159. https://doi.org/10.17219/dmp/91406
- Yang, K.-J., Son, J., Jung, S. Y., Yi, G., Yoo, J., Kim, D. K., & Koo, H. (2018). Optimized phospholipid-based nanoparticles for inner ear drug delivery and therapy. Biomaterials, 171, 133–143. https://doi.org/10.1016/j.biomaterials.2018.04.038
- Yao, Z., Huang, Y., Luo, G., Wu, J., & He, W. (2014). A biological membrane-based novel excisional wound-splinting model in mice (with video). Burns Trauma, 2(4), 196–200. https://doi.org/10.4103/2321-3868.143625
- Yıldırım, S., Özener, H., Doğan, B., & Kuru, B. (2018). Effect of topically applied hyaluronic acid on pain and palatal epithelial wound healing: An examiner-masked, randomized, controlled clinical trial. Journal of Periodontology, 89(1), 36–45. https://doi.org/10.1902/jop.2017.170105
- Yussif, N., Wagih, R., & Selim, K. (2021). Propylene mesh versus acrylic resin stent for palatal wound protection following free gingival graft harvesting: A short-term pilot randomized clinical trial. BMC Oral Health, 21(1), 208. https://doi.org/10.1186/s12903-021-01541-z
- Zucchelli, G., Tavelli, L., McGuire, M. K., Rasperini, G., Feinberg, S. E., Wang, H. L., & Giannobile, W. V. (2020). Autogenous soft tissue grafting for periodontal and peri-implant plastic surgical reconstruction. Journal of Periodontology, 91(1), 9–16. https://doi.org/10.1002/jper.19-0350