Journal September 25, 2026 5 min read

Which Peptides Are Studied in Relation to Microneedling?

A research-supply review of the compounds investigated alongside microneedling, including tranexamic acid, metformin, glutathione, hyaluronic acid, and polynucleotides such as PDRN.

peptides-pro Editorial

The compounds most frequently studied in relation to microneedling are not, strictly speaking, all peptides. The literature indexed in the evidence base centres on tranexamic acid (TXA), a synthetic lysine derivative with the molecular formula C8H15NO2 and a molecular weight of approximately 157.2 g/mol, supplied in the cited trial as a 100 mg/mL topical ampoule formulation [1]. Alongside it sit metformin, glutathione, hyaluronic acid, and the polynucleotide class — most notably polydeoxyribonucleotide (PDRN), a DNA-derived polymer obtained from salmon or trout [3]. These are the agents that appear in registered protocols where microneedling is used as the delivery or disruption step.

The mechanistic thread running through this work is not a single receptor family but the physical bypass of the stratum corneum, which is the principal barrier to transdermal delivery [9]. Once that barrier is disrupted, the studied endpoints cluster around pigmentary pathways, inflammatory signalling, and connective-tissue remodelling — including tissue levels of platelet-derived growth factor (PDGF) and connective tissue growth factor (CTGF) in hypertrophic scar models [6].

Research Studies

Tranexamic acid and striae rubra in a split-side clinical trial

A registered trial evaluates microneedling with topical tranexamic acid against microneedling with placebo in striae rubra [1]. The intervention side receives TXA at 100 mg/mL followed by a microneedling session; the contralateral control side receives 0.9% normal saline followed by microneedling performed in the same manner. Sessions are scheduled every three weeks, up to a maximum of five, depending on the protocol's stopping criteria [1]. The split-side design is notable because it uses each participant as their own control, isolating the contribution of the topical agent from that of the needling itself.

Tranexamic acid, metformin and modified Kligman's formula in melasma

A separate randomized, parallel-group trial compares microneedling-assisted topical metformin, topical tranexamic acid, and modified Kligman's formula against microneedling-assisted saline in adult women with melasma [2]. Eighty participants are randomly assigned across four treatment groups. The primary outcome is change in Melasma Area and Severity Index (MASI) score from baseline to end of follow-up [2]. This is one of the few head-to-head designs in the evidence set, and it places two non-peptide small molecules and a multi-agent topical formula in direct comparison.

Agent	Comparator	Population	Primary outcome
Topical metformin	Microneedling + saline	Adult women with melasma	MASI change [2]
Topical tranexamic acid	Microneedling + saline	Adult women with melasma	MASI change [2]
Modified Kligman's formula	Microneedling + saline	Adult women with melasma	MASI change [2]

Glutathione gel and gingival depigmentation in a split-mouth trial

Gingival colour is described as a determinant of smile aesthetics, and gingival depigmentation has gained popularity among periodontal plastic procedures over the past decade [4]. A split-mouth clinical trial compares microneedling alone with microneedling combined with glutathione gel for this indication [4]. The split-mouth format mirrors the split-side design used in the striae work, again separating the mechanical effect from the topical contribution.

Hyaluronic acid and thin gingival phenotype

A trial evaluates microneedling alone versus microneedling with hyaluronic acid in thin gingival phenotype [5]. The periodontal phenotype is defined as the combination of gingival phenotype and buccal bone plate thickness, and while the full phenotype cannot be completely assessed, gingival phenotype can be evaluated in a standard and reproducible way [5]. Gingival recession is typically observed with trauma and inflammation in thin phenotypes, whereas pocket formation is reported in thick phenotypes [5]. Conventional soft tissue augmentation — subepithelial connective tissue graft, free gingival graft, modified roll technique, and acellular dermal matrix — carries the drawback of a second surgical site [5], which is the rationale context for testing a less invasive adjunct.

Polynucleotides and PDRN in skin booster formulations

Skin boosters are injectable and topical treatments intended to improve dermal quality and restore skin health, and the category typically includes hyaluronic acid formulations, biostimulatory agents, platelet-rich plasma, growth factors, and polynucleotides [3]. PDRN, derived from salmon or trout DNA, is described as exhibiting dual regenerative and anti-inflammatory properties, promoting tissue repair by supplying nucleotides essential for DNA synthesis [3]. This is the closest the evidence base comes to a true peptide-adjacent polymer class in the microneedling context.

PDGF and CTGF in hypertrophic scar models

A comparative study examines fractional microneedling radiofrequency versus intralesional steroid injection, with and without microneedling, on tissue levels of PDGF and CTGF in hypertrophic scars [6]. These two growth factors are the only named molecular endpoints in the evidence set, and they anchor the scar-remodelling arm of the literature.

Permeability enhancement in ex vivo human skin models

An ex vivo evaluation assessed skin permeability enhancement using a cooling-assisted delivery device in human-derived skin tissue models [9]. The stratum corneum is described as a significant barrier to transdermal delivery, and the device was developed to enhance penetration, with potential synergistic effects when combined with microneedling systems including a 0.5 mm pin and a 1.5 mm MTS configuration [9]. This work is ex vivo and tissue-based, not a clinical endpoint study.

Antioxidant serum formulations and temporal application

A multicentre clinical investigation evaluated complementary day and night antioxidant serums, built on the rationale that sensitive skin is linked to oxidative stress, barrier dysfunction, and disrupted skin biorhythms, and that daytime defence and nighttime repair cycles justify temporally optimized formulations [7]. This work does not centre on microneedling and is included here as supporting context for topical formulation design.

Acne-induced hyperpigmentation across skin types

A review of practical therapeutic strategies addresses post-inflammatory hyperpigmentation and post-inflammatory erythema as common sequelae of acne, particularly in individuals with skin of colour; up to 85% of patients with Fitzpatrick phototypes IV–VI develop post-inflammatory hyperpigmentation following inflammatory acne lesions [8]. This is background on the pigmentary conditions that several of the microneedling trials above are designed to treat.

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