COMPARISON OF THE EFFECTS OF PDRN, NIACINAMIDE AND HYALURONIC ACID, WHEN ASSOCIATED WITH THE MICRONEEDLING TECHNIQUE, IN THE TREATMENT OF FACIAL REJUVENATION: A SYSTEMATIC REVIEW

REGISTRO DOI: 10.70773/revistatopicos/777741809

ABSTRACT
Objective: To compare the efficacy of PDRN, niacinamide, and hyaluronic acid when associated with the microneedling technique in the treatment of facial rejuvenation. Materials and Methods: A systematic literature review with a qualitative–quantitative approach was carried out. Scientific articles were searched in the PubMed, ScienceDirect, Cochrane Library, and SciELO databases. Results: The analysis of the articles demonstrated that all the studied agents presented positive effects in facial rejuvenation when combined with microneedling. PDRN stood out for tissue regeneration and cellular biostimulation; niacinamide for its antioxidant, depigmenting, and DNA-protective effects; and hyaluronic acid for deep hydration and improvement of dermal texture and support. Conclusion: It was found that the association of microneedling with the agents PDRN, niacinamide, and hyaluronic acid constitutes a promising, safe, and effective approach for facial rejuvenation. Although all present complementary benefits, PDRN demonstrated greater regenerative potential, niacinamide greater versatility, and hyaluronic acid remains a reference for hydration and superficial filling.
Keywords: Skin biostimulation; Tissue regeneration; Neocollagenesis; Transdermal drug delivery; Aesthetic dermatology.

RESUMO
Objetivo: Comparar a eficácia do PDRN, da niacinamida e do ácido hialurônico quando associados à técnica de microagulhamento no tratamento do rejuvenescimento facial. Materiais e Métodos: Foi realizada uma revisão sistemática da literatura com abordagem qualitativa-quantitativa. Artigos científicos foram pesquisados ​​nas bases de dados PubMed, ScienceDirect, Cochrane Library e SciELO. Resultados: A análise dos artigos demonstrou que todos os agentes estudados apresentaram efeitos positivos no rejuvenescimento facial quando combinados com o microagulhamento. O PDRN destacou-se pela regeneração tecidual e bioestimulação celular; a niacinamida, por seus efeitos antioxidantes, despigmentantes e de proteção do DNA; e o ácido hialurônico, pela hidratação profunda e melhora da textura e sustentação dérmica. Conclusão: Constatou-se que a associação do microagulhamento com os agentes PDRN, niacinamida e ácido hialurônico constitui uma abordagem promissora, segura e eficaz para o rejuvenescimento facial. Embora todos apresentem benefícios complementares, o PDRN demonstrou maior potencial regenerativo, a niacinamida maior versatilidade e o ácido hialurônico permanece como referência para hidratação e preenchimento superficial.
Palavras-chave: Bioestimulação da pele; Regeneração tecidual; Neocolagênese; Administração transdérmica de medicamentos; Dermatologia estética.

INTRODUCTION

The search for interventions that promote facial rejuvenation has been intensified by the social valorization of youth and aesthetics, translated into a growing demand for minimally invasive procedures that provide effective and safe results.

Among these interventions, the microneedling technique stands out, which consists of the percutaneous induction of collagen through multiple perforations in the skin, promoting tissue regeneration. Associated with this technique, the use of agents such as PDRN (polydeoxyribonucleotide), niacinamide (vitamin B3), and hyaluronic acid has become a promising strategy to enhance the desired clinical effects.

In this context, the present research proposes to answer the following question: what is the efficacy of PDRN, niacinamide, and hyaluronic acid, when associated with the microneedling technique, in the treatment of facial rejuvenation? Thus, the general objective of this study is to compare the effects of these three agents in facial rejuvenation when used in conjunction with the microneedling technique.

The specific objectives are: to identify the main mechanisms of action of PDRN, niacinamide, and hyaluronic acid in facial rejuvenation; to analyze the clinical benefits of the association of these agents with microneedling; and to compare the results reported in the literature regarding the regenerative, antioxidant, and hydrating efficacy of these agents.

This study is justified by the growing relevance of microneedling associated with dermocosmetic agents in the aesthetic market, estimated at 89.64 billion dollars in 2024, with a projection to reach 239.98 billion dollars in 2033,¹ as well as by the scarcity of comparative studies that support the selection of therapeutic protocols according to the objectives of the treatment and the individual characteristics of the patients. In this context, the present systematic review analyzes the effects of these agents associated with microneedling in facial rejuvenation, contributing to technical-scientific strengthening and to a safer practice in the area of orofacial harmonization.

METHODOLOGY

This is a descriptive literature review with a qualitative–quantitative approach. Therefore, a search was carried out in the Scientific Electronic Library Online (SciELO), PubMed, ScienceDirect, and Cochrane Library databases, between the months of February and April 2025.

Scientific articles published in English and Portuguese were selected, filtered by the following descriptors: PDRN, Niacinamide, Hyaluronic Acid, Microneedling, and Facial Rejuvenation, combined by the Boolean operators AND and OR.

All original articles indexed with an experimental design (clinical trial — randomized or not) or observational (before-and-after studies, case-control studies) were included. Duplicate articles not available in full text, in full, and articles that did not address the use of the agents PDRN, niacinamide, and hyaluronic acid in interaction with the microneedling technique in the treatment of facial rejuvenation were excluded.

During the search, a technical reading of the resulting articles was carried out, a fundamental stage of the analysis of the material, guided by the inclusion and exclusion criteria, in which titles, abstracts, and keywords were examined, as well as information related to the publication, with a view to ensuring the indexing of the work. The obtained data were imported into a spreadsheet through a specialized program and, subsequently, subjected to descriptive analysis of the content, with the objective of translating them into statistical data of absolute and relative frequency, presented in a table attached to this work. Finally, the selected articles were evaluated regarding adherence to the theme, originality, and methodological quality, according to the flowchart presented in Image 1 (Appendices).

It is worth noting that this systematic review did not delimit specific age groups, sex, or phototypes, and did not seek to analyze differences in effects between men and women, nor between young or elderly individuals. The focus of the research was exclusively on comparing the clinical effects reported in the selected studies, without population segmentation, aiming to obtain an overview of the performance of the agents associated with microneedling in facial rejuvenation.

RESULTS

Among the twenty studies included in this stage (described in Table 1), different approaches were observed regarding the type of sample, frequency of applications, concentrations used, and follow-up time. The studies, originating from journals of dermatology, regenerative medicine, and aesthetic surgery, include both randomized clinical trials and systematic reviews, in vitro studies, and case series, focusing on visual, sensory, and histological parameters. The organization of the selected articles reveals that the investigation of biocompounds applied to facial rejuvenation has been consolidated based on multiple experimental and clinical strategies.

Table 1 – Studies included in the review

Source: Donato, Aurita, (2026).

DISCUSSION

The microneedling technique

Microneedling is a minimally invasive aesthetic procedure that consists of creating controlled microlesions in the skin, causing disruption of the cutaneous barriers. This process triggers an inflammatory response that stimulates collagen production (neocollagenesis), neovascularization, and elastin synthesis, in addition to creating microchannels that significantly increase skin permeability for topical agents.²²

The microneedling technique was first introduced in 1995 in South Africa (Cape Town), during a local medical congress, by the surgeon Desmond Fernandes,²³ who developed the Dermaroller in 1997.²⁴ The device consists of a cylinder containing 190 to 1080 stainless steel needles, attached to a polypropylene handle, which makes sterilization of the equipment unfeasible, therefore being intended for disposable use.²⁵

Another device used is the Dermapen, which operates with disposable microneedles in cartridges, producing vibratory movements that allow greater precision. The needles used may be made of stainless steel or titanium, ranging from 190 to 450 units. Both the Dermaroller and the Dermapen have depths ranging from 0.25 mm to 2.5 mm; from 2.0 mm onwards, use is restricted to medical professionals.²⁶

The induced microlesions facilitate the absorption of active agents, optimizing treatment protocols for facial rejuvenation, namely: skin flaccidity, wrinkles, expression lines, and improvement of skin texture and luminosity.²⁷ During application, force is applied, but it is not yet standardized, as it depends on the thickness of the stratum corneum and the skin biotype.

Microneedling using Dermaroller or Dermapen is not recommended for individuals with active skin infections, tendency to develop keloids, coagulation disorders, herpes zoster, pregnant or lactating women, or patients with uncontrolled autoimmune diseases.²⁸

The procedure involves: (a) anamnesis: a thorough analysis of the area to be treated, considering thickness, biotype (especially skin phototypes V and VI), and clinical functional physiology; (b) asepsis: cleaning, exfoliation, and hygiene of the site; (c) application: use of the Dermapen with adjustment of needle depth according to the treated region (the 36-needle cartridge is usually the most indicated for facial rejuvenation treatment).²⁹ During the technique, the Dermapen device or Dermaroller must be moved horizontally and vertically, longitudinally to the right and to the left, in an average of 10 to 15 passes, applying appropriate force according to the region and the objective of the treatment. After evaluating the skin response (for example, the presence of hyperemia and redness), the professional must inform the patient about these responses and may then proceed to other areas. The entire process must be documented with photographs (before and after). The cartridges used must, obligatorily, be sterile, disposable, and registered with ANVISA.³⁰

Facial rejuvenation treatment using the microneedling technique may require three to six sessions, respecting the interval between sessions (28 to 30 days), also referred to as the dermal cycle.

Since the previously mentioned medical congress, microneedling has evolved into more advanced models, such as robotic microneedling associated with radiofrequency microneedling, which offers more effective results in aesthetic treatments, especially facial ones.³¹

The needles used in robotic microneedling are gold-coated, through which radiofrequency is delivered during the procedure.³² With radiation ranging between 60° and 70°, this thermogenic technique stimulates neocollagenesis at the level of the reticular dermis, promoting type I collagen production. Integrated into the concept of drug delivery, the technique facilitates the penetration of agents such as PDRN, niacinamide, and hyaluronic acid, promoting deep hydration and epidermal renewal, in addition to acting in the treatment of flaccidity and infraorbital and periorbital wrinkles (areas that require increased attention regarding speed).³³

More recent studies on the microneedling technique in facial rejuvenation have employed modern microneedling pens, such as Dr. Pen A20 and Dermapen 4 (Figures 1 and 2 attached), according to the studies by Gordon H. Sasaki³⁴ and José A. Foppiani.³⁵

PDRN

Regenerative aesthetics is an emerging field within Dermatology and Aesthetic Medicine, which focuses on tissue repair, cellular biostimulation, and modulation of inflammation, aiming to restore the integrity and functionality of the skin.

Among innovative biotechnological agents, polydeoxyribonucleotide (PDRN) stands out, a compound derived from salmon DNA with potent regenerative properties. It has a DNA fraction with a molecular weight ranging from 50–1500 kDa, being mainly obtained from the sperm of the salmon Oncorhynchus keta, through enzymatic purification techniques.³⁶

The combination with other agents, such as hyaluronic acid, through the microneedling technique in skin treatment and regeneration, has achieved synergistic effects and stimulation of type II and V collagen, in addition to facial rejuvenation, antioxidant action, and neocollagenesis in facial aesthetic treatments.³⁷

PDRN is presented as a polymer of deoxyribonucleotides which, when applied topically or injected, acts in DNA and RNA synthesis during the tissue regeneration process. Among the observed benefits are: improvement of skin elasticity and firmness, reduction of fine lines and expression lines, dermal restructuring after procedures such as laser or microneedling, and promotion of collagen remodeling.³⁸

Regarding administration, it may be performed by: (a) intradermal route (mesotherapy); (b) topical application associated with microneedling or fractional radiofrequency; (c) combination with hyaluronic acid and niacinamide, with synergistic effect. The agent presents a high level of safety, low risk of immunogenicity, compatibility with other bioactive compounds, and mild adverse reactions (erythema and local edema)³⁹

PDRN represents a significant advancement in regenerative aesthetics, offering a safe, effective, and physiological approach to skin revitalization and tissue regeneration. Its therapeutic versatility and profound biological mechanisms consolidate it as a pillar in regenerative and genetic therapies and in the management of protocols in advanced aesthetics, making it promising in orofacial harmonization, with growing potential in combined protocols.⁴⁰

In Brazil, the use of PDRN began approximately 15 years ago, mainly focused on medical applications in regenerative therapies. In its early uses, it was associated with the regeneration of bone, skin, and joint tissues, in addition to assisting in the management of chronic pain.

Niacinamide

For more than seven decades, vitamin B3 (niacinamide) has been used as a supplement. The discovery of its aesthetic potential occurred through its use in the treatment of pellagra, a disease known as the three Ds: dementia, dermatitis, and diarrhea.

Currently, it presents a protective effect against DNA damage induced by UV radiation in epidermal melanocytes⁴¹ and acts to enhance the effect of individual compounds, such as PDRN and hyaluronic acid, when used in the treatment of photoaging through the microneedling technique. Studies indicate topical applications with excellent results, including in serum form, according to research conducted using the microneedling technique with the Dermapen device equipped with a 36-needle cartridge.⁴²

This protective effect against DNA damage increases type I, II, and V collagen, optimizing neocollagenesis, making this agent an ally in skin management in orofacial harmonization procedures, preparing the skin and prolonging the durability of facial procedures in HOF.⁴³

Hyaluronic Acid

Aging reduces the production of hyaluronic acid (HA) in the skin, triggering the appearance of wrinkles and the process of skin flaccidity. Present in various connective tissues, this glycosaminoglycan is known for its water-retention capacity and is therefore a key component of the extracellular matrix, providing structural support and playing a crucial role in maintaining skin integrity.⁴⁴

Injectable products based on hyaluronic acid have demonstrated efficacy in reducing wrinkles and improving skin hydration and radiance. Skin hydration is essential to keep it nourished and healthy, helping it perform its primary function, which is to retain molecules, resulting in skin with a youthful and healthy appearance, with glow and vitality.⁴⁵

Hyaluronic acid has been the focus of significant interest in dermatology and advanced aesthetic research due to its potential benefits, including the reduction of expression wrinkles. Another analyzed benefit is the stimulation of fibroblast growth, resulting in increased production of collagen and elastin, contributing to skin firmness.⁴⁶

Studies by Zhou et al.⁴⁷ demonstrate that treatments associated with hyaluronic acid, at the correct dosage and timing in patients with aged skin, contribute to skin radiance, luminosity, and nourishment, thus confirming its efficacy in facial rejuvenation treatment.

CONCLUSION

The present systematic review demonstrated that the association of microneedling with the agents PDRN, niacinamide, and hyaluronic acid constitutes an effective approach for facial rejuvenation, since each substance presents complementary mechanisms of action. PDRN stands out for its role in tissue regeneration and cellular biostimulation; niacinamide for its antioxidant, depigmenting, and DNA-protective effects; and hyaluronic acid for promoting deep hydration, improvement of skin texture, and dermal support. The choice of the most appropriate agent depends on individual clinical needs and therapeutic objectives, with hyaluronic acid being widely established in protocols for hydration and superficial rejuvenation.

Despite the promising results, there is a need for more robust and standardized clinical studies to establish safe parameters regarding the concentration, frequency, and method of application of these agents associated with microneedling. Although the scarcity of direct comparative studies limits definitive conclusions, the available findings provide relevant support for improving clinical practice in orofacial harmonization, contributing to safer, more effective, and scientifically grounded therapeutic decisions.

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APPENDICES

Figure 1 - Prism Flowchart 2020

Figure 2 - Comparison table of the effects of active ingredients on facial rejuvenation

ANEXOS

Image 1: Dr. Pen A20 - (FDN registration: K230420)

Image 2: Dermapenword 4 - (registrations: FDA-cleared (K510), CE Mark and TFDA)

Image 3: Mechanism of action of microneedle radiofrequency

¹ Student in the International Master’s Program in Orofacial Harmonization at the European Face & Body Institute, located at: Rua do Cabo Espichel, 570, Porto/Portugal. E-mail: [clique para visualizar o e-mail]acesse o artigo original para visualizar o e-mail

² Professor in the International Master’s Program in Orofacial Harmonization at the European Face & Body Institute, located at: Rua do Cabo Espichel, 570, Porto/Portugal. E-mail: [clique para visualizar o e-mail]acesse o artigo original para visualizar o e-mail

³ Professor in the Lollobrigida Health Institute and Academic Advice/translation into English, located at: 15000 Stratus Loop, Winter Garden, USA. E-mail: [clique para visualizar o e-mail]acesse o artigo original para visualizar o e-mail