Collagen Restoration from Combined Radiofrequency Microneedling and Polydioxanone Filler in Oxidative Stress-Mediated Skin Aging

Ruth Agustina Sinaga, Cindra Paskaria, Wahyu Widowati

Abstract


BACKGROUND: Oxidative stress plays a central role in skin aging by promoting reactive oxygen species–mediated collagen degradation, fibroblast senescence, and dermal thinning. Although radiofrequency microneedling (RFM) and polydioxanone (PDO) filler individually stimulate collagen remodeling, evidence regarding their combined efficacy in oxidative stress induced skin aging models remains limited. This study evaluated the effects of combined RFM and PDO filler therapy in a D-galactose–induced oxidative stress model of skin aging.

METHODS: Thirty female Sprague-Dawley rats were randomly assigned into five groups (n=5): normal control (NC), aging control (AC), RFM monotherapy, PDO monotherapy, and combination therapy. Oxidative aging was induced by daily intraperitoneal injections of 50 mg/kg for 8 weeks, followed by a single post-induction treatment session. Skin samples were collected at 12 weeks post-treatment for histological assessment of dermal thickness (hematoxylin–eosin), collagen density (Masson’s trichrome), and fibroblast count.

RESULTS: D-galactose significantly reduced dermal thickness, collagen density, and fibroblast count in AC compared with NC (p<0.001). All treatment groups showed significant improvement versus AC (p<0.05). Notably, only the combination therapy restored collagen density to a level comparable with normal skin (35.22 [28.74–40.35]% vs. 37.83 [33.11–40.69]%, p=0.124). The combination group also showed the highest increases in dermal thickness and fibroblast numbers among treatment groups.

CONCLUSION: In this preclinical model, combined RFM and PDO filler therapy demonstrated enhanced restoration of dermal structure and collagen under oxidative stress–mediated skin aging, supporting its potential role in skin rejuvenation strategies.

KEYWORDS: collagen density, dermal regeneration, D-galactose, oxidative stress, skin aging


Full Text:

PDF

References


Russell-Goldman E, Murphy GF. The pathobiology of skin aging. Am J Pathol. 2020; 190(7): 1356-69, CrossRef.

Gu Y, Han J, Jiang C, Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev. 2020; 59: 101036, CrossRef.

Azman KF, Zakaria R. D-Galactose-induced accelerated aging model: An overview. Biogerontology. 2019; 20(6): 763-82, CrossRef.

Umbayev B, Askarova S, Almabayeva A, Saliev T, Masoud AR, Bulanin D. Galactose-induced skin aging: the role of oxidative stress. Oxid Med Cell Longev. 2020; 2020: 7145656, CrossRef.

Ho SC, Liu JH, Wu RY. Establishment of the mimetic aging effect in mice caused by D-galactose. Biogerontology. 2003; 4(1): 15-8, CrossRef.

Tan MG, Jo CE, Chapas A, Khetarpal S, Dover JS. Radiofrequency microneedling: A comprehensive and critical review. Dermatol Surg. 2021; 47(6): 755-61, CrossRef.

Xu Y, Zhang Y, Wang H, Tang H, Zeng W, Wen X. Microneedle radiofrequency induces extracellular matrix remodeling through fibroblast activation: a histological study in a porcine model. Lasers Surg Med. 2025; 57(6): 528-43, CrossRef.

Kwon T, Han SW, Yeo IK, Kim JH, Kim JM, Hong J, et al. Biostimulatory effects of polydioxanone, poly-d,l-lactic acid, and polycaprolactone fillers in mouse model. J Cosmet Dermatol. 2019; 18(4): 1002-8, CrossRef.

Zhou SY, Kang SM, Gu YJ, Zhang XR, Yon DK, Shin BH, et al. Bio-characteristics and efficacy analysis of biodegradable poly dioxanone dermal filler in a mouse model and humans. In Vivo. 2023; 37(3): 1093-102, CrossRef.

Jin Y, Lee YH, Kim DH, Jin C, Zhang X, Yoo JR, et al. Synergistic CO₂ cryotherapy and EGF delivery for accelerated wound healing through anti-inflammatory and regenerative pathways. Int J Mol Sci. 2025; 26(18): 8796, CrossRef.

Song H, Fu F, Chen Y, Yang R, Luo Z, Shao J, et al. A poly(lipoic acid)-based elastomer adhesive with synergistic activity of microenvironment regulation and peripheral neuropathy repair facilitates infectious diabetic wound healing. Biomaterials. 2026; 324: 123489, CrossRef.

Wu X, Cen Q, Wang X, Xiong P, Wu X, Lin X. Microneedling radiofrequency enhances poly-L-lactic acid penetration that effectively improves facial skin laxity without lipolysis. Plast Reconstr Surg. 2024; 154(6): 1189-97, CrossRef.

Seo KY, Yoon MS, Kim DH, Lee HJ. Skin rejuvenation by microneedle fractional radiofrequency treatment in Asian skin; clinical and histological analysis. Lasers Surg Med. 2012; 44(8): 631-6, CrossRef.

Kim H, Park KY, Choi SY, Koh HJ, Park SY, Park WS, et al. The efficacy, longevity, and safety of combined radiofrequency treatment and hyaluronic acid filler for skin rejuvenation. Ann Dermatol. 2014; 26(4): 447-56, CrossRef.

Sgonc R, Gruber J. Age-related aspects of cutaneous wound healing: A mini-review. Gerontology. 2013; 59(2): 159-64, CrossRef.

Russell WMS, Burch RL. The Principles of Humane Experimental Technique. London: Methuen; 1959, NLMID.

Chen J, Li Y, Zhu Q, Li T, Lu H, Wei N, et al. Anti-skin-aging effect of epigallocatechin gallate by regulating epidermal growth factor receptor pathway on aging mouse model induced by d-galactose. Mech Ageing Dev. 2017; 164: 1-7, CrossRef.

Wang H, Wei S, Xue X, You Y, Ma Q. Adipose stem cells' antagonism in glycosylation of D-galactose-induced skin aging of nude mice and its skin recovery function. Int J Immunopathol Pharmacol. 2016; 29(3): 376-85, CrossRef.

Kim HK, Kim HJ, Kim JY, Ban MJ, Son J, Hwang Y, et al. Immediate and late effects of pulse widths and cycles on bipolar, gated radiofrequency-induced tissue reactions in in vivo rat skin. Clin Cosmet Investig Dermatol. 2023; 16: 721-9, CrossRef.

Kwon T, Han SW, Yeo IK, Kim JH, Kim JM, Hong J, et al. Biostimulatory effects of polydioxanone, poly-d,l-lactic acid, and polycaprolactone fillers in mouse model. J Cosmet Dermatol. 2019; 18(4): 1002-8, CrossRef.

Widowati W, Darsono L, Lucianus J, Setiabudi E, Obeng SS, Stefani S, et al. Butterfly pea flower (Clitoria ternatea L.) extract displayed antidiabetic effect through antioxidant, anti-inflammatory, lower hepatic GSK-3β, and pancreatic glycogen on diabetes mellitus and dyslipidemia rat. J King Saud Univ Sci. 2023; 35(4): 102579, CrossRef.

Islam MA, Kumar S. Masson's trichrome staining technique to evaluate tissue fibrosis. In: Fibrosis: Methods and Protocols. New York: Humana Press; 2026. p.91-100, CrossRef.

Inforzato HCB, Carbonel AAF, Simões RS, da Silva Sasso GR, Azevedo Lima PD, Soares-Júnior JM, et al. Histomorphometric analysis of the skin of women during the reproductive period. Clinics. 2018; 73: e387, CrossRef.

Utoyo FS, Widowati W, Ratnawati H. The potency of Centella asiatica leaf extract on VEGF expression and angiogenesis in second-degree burn wound in mice. Hayati J Biosci. 2025; 32(1): 140-6, CrossRef.

Mao GX, Zheng LD, Cao YB, Chen ZM, Lv YD, Wang YZ, et al. Antiaging effect of pine pollen in human diploid fibroblasts and in a mouse model induced by D-galactose. Oxid Med Cell Longev. 2012; 2012: 750963, CrossRef.

Siswanto FM. Resveratrol protects Caenorhabditis elegans from ultraviolet B-induced photoaging via skn-1. Mol Cell Biomed Sci. 2025; 9(1): 48-57, CrossRef.

Girsang E, Lister IN, Ginting CN, Bethasari M, Amalia A, Widowati W. Comparison of antiaging and antioxidant activities of protocatechuic and ferulic acids. Mol Cell Biomed Sci. 2020; 4(2): 68-75, CrossRef.

Valentina I, Achadiyani A, Adi SS, Lesmana R, Farenia R. Effect of Lactobacillus reuteri administration on wrinkle formation and type I procollagen levels in UVB-exposed male Balb/c mice (Mus musculus). Mol Cell Biomed Sci. 2020; 4(3): 113-20, CrossRef.

Wang Q, Ma C, Zhang L. A scoping review of radiofrequency microneedling: clinical application and outcome assessment. Aesthetic Plast Surg. 2025; 49(18): 5199-210, CrossRef.

Meiliana A, Dewi NM, Wijaya A. Mitochondrial dysfunction in stem cell aging. Indones Biomed J. 2015; 7(1): 15-30, CrossRef.

Meiliana A, Dewi NM, Wijaya A. Stem cell quiescence versus senescence: the key for healthy aging. Indones Biomed J. 2021; 13(4): 337-49, CrossRef.

Dewi DA, Sandra F. Conditioned media of human umbilical cord blood mesenchymal stem cell inhibits ultraviolet B-induced apoptosis in fibroblasts. Indones Biomed J. 2019; 11(1): 85-90, CrossRef.

Wu X, Cen Q, Wang X, Xiong P, Wu X, Lin X. Microneedling radiofrequency enhances poly-L-lactic acid penetration that effectively improves facial skin laxity without lipolysis. Plast Reconstr Surg. 2024; 154(6): 1189-97, CrossRef.

Zhu Q, Zhu L, Lang J, Zhu J, Chen D, Huang Y, et al. Dopamine-functionalized bioinspired pre-chondrogenic hydrogel for cell-free cartilage regeneration. J Control Release. 2026; 389: 114407, CrossRef.




DOI: https://doi.org/10.18585/inabj.v18i2.4024

Copyright (c) 2026 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 Indexed by:

                  

                     

          

 

 

The Prodia Education and Research Institute