In Vitro Wound Healing Properties of Novel Acidic Treatment Regimen in Enhancing Metabolic Activity and Migration of Skin Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jul 9

PMID 35806191

Authors

Pivian Sim

Yunmei Song

Gink N Yang

Allison J Cowin

Sanjay Garg

Affiliations

Soon will be listed here.

Abstract

Strategies that alter the pH of wounds to improve healing outcomes are an emerging area of interest. Currently, there is limited understanding of the effect of hydrogen (H) on the functionality of skin cells during proliferation and migration, highlighting the need for research to determine the effect of pH during wound healing. This study aimed to determine the effect of acidification on the metabolic activity and migration of human immortalized keratinocytes (HaCaT) and human foreskin fibroblasts (HFF). In vitro models were used with phosphoric and citric acid buffers at a pH range between 3 and 7. Our results showed that cells were more viable in buffers with low rather than high ionic strength. A time-dependent effect of the acidification treatment was also observed with cell metabolic activity varying with treatment duration and frequency. Our results showed that a 24 h treatment and subsequent resting phase significantly improved cell proliferation and migration. This in vitro study is the first to establish a correlation between the role of acidic pH, molarity and treatment regimen in cellular activity. Our data demonstrated a positive effect of acidic pH on cell metabolic activity and migration rate, suggesting a clinical potential in indications such as wound healing.

Citing Articles

The Acid-Buffered Engineered Gel Promotes In Vitro Cutaneous Healing and Fights Resistant Bacteria in Wounds.

Abid F, Virgo E, Kennewell T, Khetan R, Haidari H, Kopecki Z Pharmaceutics. 2024; 16(11).

PMID: 39598606 PMC: 11597482. DOI: 10.3390/pharmaceutics16111484.

Physically Cross-Linked PVA Hydrogels as Potential Wound Dressings: How Freezing Conditions and Formulation Composition Define Cryogel Structure and Performance.

Gorska A, Baran E, Knapik-Kowalczuk J, Szafraniec-Szczesny J, Paluch M, Kulinowski P Pharmaceutics. 2024; 16(11).

PMID: 39598512 PMC: 11597501. DOI: 10.3390/pharmaceutics16111388.

EHO-85, Novel Amorphous Antioxidant Hydrogel, Containing Leaf Extract-Rheological Properties, and Superiority over a Standard Hydrogel in Accelerating Early Wound Healing: A Randomized Controlled Trial.

Verdu-Soriano J, de Cristino-Espinar M, Luna-Morales S, Dios-Guerra C, Casado-Diaz A, Quesada-Gomez J Pharmaceutics. 2023; 15(7).

PMID: 37514112 PMC: 10383111. DOI: 10.3390/pharmaceutics15071925.

N,N-Dimethylglycine Sodium Salt Exerts Marked Anti-Inflammatory Effects in Various Dermatitis Models and Activates Human Epidermal Keratinocytes by Increasing Proliferation, Migration, and Growth Factor Release.

Lendvai A, Beke G, Hollosi E, Becker M, Volker J, Schulze Zur Wiesche E Int J Mol Sci. 2023; 24(14).

PMID: 37511024 PMC: 10379135. DOI: 10.3390/ijms241411264.

Physical Properties and pH Environment of Foam Dressing Containing Leaf Extract and Gelatin.

Hasatsri S, Suthi J, Siriwut N, Charoensappakit O Pharmaceuticals (Basel). 2023; 16(5).

PMID: 37242467 PMC: 10222729. DOI: 10.3390/ph16050685.

References

Pipelzadeh M, Naylor I . The in vitro enhancement of rat myofibroblast contractility by alterations to the pH of the physiological solution. Eur J Pharmacol. 1998; 357(2-3):257-9. DOI: 10.1016/s0014-2999(98)00588-3. View

Ying H, Zhou J, Wang M, Su D, Ma Q, Lv G . In situ formed collagen-hyaluronic acid hydrogel as biomimetic dressing for promoting spontaneous wound healing. Mater Sci Eng C Mater Biol Appl. 2019; 101:487-498. DOI: 10.1016/j.msec.2019.03.093. View

Kaufman T, Eichenlaub E, Angel M, Levin M, Futrell J . Topical acidification promotes healing of experimental deep partial thickness skin burns: a randomized double-blind preliminary study. Burns Incl Therm Inj. 1985; 12(2):84-90. DOI: 10.1016/0305-4179(85)90032-4. View

Hsu Y, Liu K, Yeh H, Lin H, Wu H, Tsai J . Sustained release of recombinant thrombomodulin from cross-linked gelatin/hyaluronic acid hydrogels potentiate wound healing in diabetic mice. Eur J Pharm Biopharm. 2018; 135:61-71. DOI: 10.1016/j.ejpb.2018.12.007. View

Gethin G, Cowman S, Conroy R . The impact of Manuka honey dressings on the surface pH of chronic wounds. Int Wound J. 2008; 5(2):185-94. PMC: 7951475. DOI: 10.1111/j.1742-481X.2007.00424.x. View

Lengheden A, Jansson L . pH effects on experimental wound healing of human fibroblasts in vitro. Eur J Oral Sci. 1995; 103(3):148-55. DOI: 10.1111/j.1600-0722.1995.tb00016.x. View

Soong H, Parkinson W, Bafna S, Sulik G, Huang S . Movements of cultured corneal epithelial cells and stromal fibroblasts in electric fields. Invest Ophthalmol Vis Sci. 1990; 31(11):2278-82. View

Chen X, Lv Q, Liu Y, Deng W . Effect of Food Additive Citric Acid on The Growth of Human Esophageal Carcinoma Cell Line EC109. Cell J. 2017; 18(4):493-502. PMC: 5086328. DOI: 10.22074/cellj.2016.4716. View

Kruse C, Singh M, Targosinski S, Sinha I, Sorensen J, Eriksson E . The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study. Wound Repair Regen. 2017; 25(2):260-269. DOI: 10.1111/wrr.12526. View

10.

Chang P, Sulik G, Soong H, Parkinson W . Galvanotropic and galvanotaxic responses of corneal endothelial cells. J Formos Med Assoc. 1996; 95(8):623-7. View

11.

Demetriou A, LEVENSON S, Rettura G, Seifter E . Vitamin A and retinoic acid: induced fibroblast differentiation in vitro. Surgery. 1985; 98(5):931-4. View

12.

Basha S, Ghosh S, Vinothkumar K, Ramesh B, Kumari P, Mohan K . Fumaric acid incorporated Ag/agar-agar hybrid hydrogel: A multifunctional avenue to tackle wound healing. Mater Sci Eng C Mater Biol Appl. 2020; 111:110743. DOI: 10.1016/j.msec.2020.110743. View

13.

LeVEEN H, Falk G, Borek B, Diaz C, Lynfield Y, Wynkoop B . Chemical acidification of wounds. An adjuvant to healing and the unfavorable action of alkalinity and ammonia. Ann Surg. 1973; 178(6):745-53. PMC: 1355839. DOI: 10.1097/00000658-197312000-00011. View

14.

Lonnqvist S, Emanuelsson P, Kratz G . Influence of acidic pH on keratinocyte function and re-epithelialisation of human in vitro wounds. J Plast Surg Hand Surg. 2015; 49(6):346-52. DOI: 10.3109/2000656X.2015.1053397. View

15.

Ren J, Yang M, Xu F, Chen J, Ma S . Acceleration of wound healing activity with syringic acid in streptozotocin induced diabetic rats. Life Sci. 2019; 233:116728. DOI: 10.1016/j.lfs.2019.116728. View

16.

Gonzalez M, Perez-Guaita D, Correa-Royero J, Zapata B, Agudelo L, Mesa-Arango A . Synthesis and biological evaluation of dehydroabietic acid derivatives. Eur J Med Chem. 2009; 45(2):811-6. DOI: 10.1016/j.ejmech.2009.10.010. View

17.

Ohgoda O, Sakai A, Koga H, Kanai K, Miyazaki T, Niwano Y . Fibroblast-migration in a wound model of ascorbic acid-supplemented three-dimensional culture system: the effects of cytokines and malotilate, a new wound healing stimulant, on cell-migration. J Dermatol Sci. 1998; 17(2):123-31. DOI: 10.1016/s0923-1811(98)00003-6. View

18.

Bruno M, Trucchi B, Burlando B, Ranzato E, Martinotti S, Akkol E . (+)-Usnic acid enamines with remarkable cicatrizing properties. Bioorg Med Chem. 2013; 21(7):1834-43. DOI: 10.1016/j.bmc.2013.01.045. View

19.

Makvandi P, Ali G, Della Sala F, Abdel-Fattah W, Borzacchiello A . Biosynthesis and characterization of antibacterial thermosensitive hydrogels based on corn silk extract, hyaluronic acid and nanosilver for potential wound healing. Carbohydr Polym. 2019; 223:115023. DOI: 10.1016/j.carbpol.2019.115023. View

20.

Jeong H, Lee B, Lee H, Kim H, Moon M, Suh I . Negative pressure wound therapy of chronically infected wounds using 1% acetic Acid irrigation. Arch Plast Surg. 2015; 42(1):59-67. PMC: 4297808. DOI: 10.5999/aps.2015.42.1.59. View