The effectiveness of secretomes delivery using microneedling compared to laser-assisted drug delivery for facial skin rejuvenation: a systematic review

Submitted on: 01/07/2023
Approved on: 07/01/2024
Financial support: None.
Conflict of interest: None.
How to cite this article: Putri LPMV, Trifitriana M, Kurniawati Y, Toisuta RJS, Karyadi E. The effectiveness of secretomes delivery using microneedling compared to laser-assisted drug delivery for facial skin rejuvenation: a systematic review. Surg Cosmet Dermatol. 2024;16:e20240274.

Abstract

This study compared the effectiveness of secretome delivery using microneedling versus laser-assisted drug delivery for facial skin rejuvenation. The review included seven studies that demonstrated that both approaches were effective in delivering secretomes. However, microneedling had a higher patient satisfaction rate and fewer reported adverse events. We concluded that micro needling may be a more patient-friendly and safer option for facial rejuvenation. Further studies with larger sample sizes and extended follow-up periods are needed to confirm these results.

Keywords: Secretome; Laser Therapy; Systematic Review; Skin.

INTRODUCTION

Skin aging is a natural process caused by a combination of extrinsic and intrinsic factors, leading to wrinkles, loss of elasticity, and other visible changes.^1,2 One strategy to combat aging is the use of stem cells, such as amniotic membrane stem cells-conditioned medium (AMSC-CM), adipose-derived mesenchymal stem cells (ADMSCs), and human umbilical cord-derived mesenchymal stem cells-conditioned medium (hUC-MSCs-CM).^3,4 To reduce wrinkles and other photoaging-related facial deformities, AMSC-CM, ADMSC-CM, and hUC-MSCs-CM can stimulate dermal collagen production, growth factor, chemokines, dermal fibroblast proliferation and migration, and epidermal keratinocyte migration.^5,6,7

Several treatments, such as microneedling and laser therapy, can promote skin rejuvenation. The fractional CO₂ and erbium lasers are emerging technologies that show potential for improving skin rejuvenation.⁷ The microthermal zone (MTZ) of ablation in the skin facilitates penetration of topical big therapeutic molecules from the surface to the layer of interest while shortening the healing time following laser-induced tissue injury.^8,9 This study aims to compare the effectiveness of secretome delivery using microneedling versus laser-assisted drug delivery (LADD) for facial skin rejuvenation.

METHOD

A systematic review through various stages: (Figure 1)

Search strategy

We conducted a comprehensive investigation in 2023 to explore the efficacy of delivering secretome through microneedling or laser-assisted drug delivery (LADD) therapy for skin rejuvenation. The search utilized keywords such as "SECRETOME", "MESENCHYMAL STEM CELL-CONDITIONED MEDIUM", "AMSC-CM", "ADMSC-CM", "hUC-MSCs- CM", combined with "MICRONEEDLING", and "LASER ASSISTED DRUG DELIVERY", including synonyms. Electronic databases, including Pubmed, Cochrane Central Database, ClinicalTrials.gov, and Mendeley, were consulted from their inception up until June 2023. We assessed the retrieved records systematically using predetermined inclusion and exclusion criteria. Initially, four authors (LPM, MT, RJ, and EK) independently scanned all abstracts to identify relevant studies. In case of discrepancies, the remaining two authors (YK and MT) were involved in the final judgment and eligibility assessment by reviewing the full-text articles. Figure 1 provides a flowchart outlining the literature search strategy, following the Preferred Reporting Items for Systematic Reviews guidelines.

Selection Criteria

This study included all publications in 2023 that investigated the effectiveness of secretome delivery using microneedling or LADD therapy for skin rejuvenation. The selected publications consisted of original studies, excluding review articles, meta-analyses, epidemiological studies, abstracts only, non-English manuscripts, and editorials.

Data Extraction

Two independent authors (MT and LPM) performed the data extraction and quality assessment using a standardized extraction method in an Excel application.

Bias Analysis

We used the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) analysis to assess bias in several journals. Table 1 shows that all journals explicitly defined their population, intervention, comparison, and outcome criteria. Although original studies were the most prevalent, some journals exhibited bias in different aspects. One journal displayed biases in participant data, another had bias related to the intervention, one journal had biases due to missing data, and another had biases associated with reporting. Overall, all the included studies received low scores, indicating a risk of bias.

RESULTS

Study selection

Figure 1 provides an overview of the process used to select the studies. Initially, the search identified a total of 82 articles, and after removing duplicates, 18 potentially relevant articles remained. Upon reviewing the titles and abstracts, 64 articles were excluded, resulting in seven studies that met the inclusion criteria. There were no disagreements during the study selection process.

Table 1 presents the characteristics of the seven studies that met the inclusion criteria. These studies encompassed various types, including prospective studies, randomized controlled spit-face studies, and analytical experimental controlled clinical trials. Most cases and studies were conducted in Indonesia, with one study from China. Among the 268 patients included in the studies, 240 were women, while the study by Liang et al. did not specify the gender of the 28 participants. The studies used microneedling, fractional CO₂ laser, and fractional erbium:YAG laser. The secretomes employed in the studies included AMSC-CM, ADMSCs, and hUC-MSCs-CM.

The effectiveness of included studies

Table 3 shows that microneedling and LADD proved to be effective therapies for delivering secretomes. Microneedling and LADD significantly reduced wrinkles and pore size, improved pigmentation and UV spots, and enhanced moisture and elasticity starting at six weeks.

Adverse events of included studies

Table 2 indicates that both groups experienced adverse events, including erythema, pain, burning sensation, itch, and urticaria. Also, the LADD group reported acne eruption. Microneedling exhibited a higher patient satisfaction rate and lower reported adverse events than the LADD group.

The comparison of microneedling and laser therapy

Table 4 reveals that LADD was slightly more effective than microneedling in facial skin rejuvenation, although the difference was not statistically significant. Microneedling demonstrated fewer adverse events and lower costs compared to LADD.

DISCUSSION

Microneedling and LADD procedures have been used in cosmetic dermatology for several goals, including skin aging therapy. Both methods successfully construct vertical microtunnels into the dermis, allowing transdermal topical drug delivery.^6-8

LADD is widely known for its capacity to increase collagen formation and remodeling, allowing photoaged skin's aberrant collagen fibers to rearrange as needed while microneedle creates microinjury and generates a regulated skin injury with little epidermal damage, which stimulates the dermal wound healing cascade (inflammation, proliferation, and remodeling).^1,2,6

Mild erythema, localized edema, and skin peeling are the most frequent and anticipated adverse events of microneedling and typically resolve within 48 to 72 hours.⁶ Compared to microneedling, LADD had more unfavorable effects, such as longer erythema, discomfort, burning sensation, and itch. In light of these findings, dermatologists can select between Microneedling and LADD to distribute secretome, given that LADD may not be available in every clinic due to high costs, while microneedling may be available in all settings. Microneedling is a beneficial option over more invasive procedures such as laser skin resurfacing and deep chemical peeling due to its quick post-treatment recovery, low adverse events profile, and remarkable clinical results.^2,5-7 To improve the therapeutic effect further, the AMSC-CM, ADMSCs, and hUC-MSCs- CM are delivered through laser channels. These cells exert their anti-wrinkle effects by upregulating procollagen type I production and inhibiting matrix metalloproteinase 1 (MMP- 1) secretion, which is responsible for the degradation of collagen fibers. The current study breaks down the skin barrier.^4,5

CONCLUSION

Microneedling and laser-assisted drug delivery are effective methods for delivering secretomes for skin rejuvenation. However, microneedling may be a more patient-friendly and safer option. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings.

AUTHOR'S CONTRIBUTION:

Luh Putu Mahatya Valdini Putri
ORCID: 0009-0008-8870-7700
Study design and planning; Preparation and writing of the manuscript; Collecting, analyzing, and interpreting data; Effective participation in research orientation; Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; Critical literature review.
Monica Trifitriana
ORCID: 0000-0002-9454-1961
Statistical analysis; Approval of the final version of the manuscript; Study design and planning; Preparation and writing of the manuscript; Collecting, analyzing, and interpreting data; Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; Critical literature review; Critical review of the manuscript.
Yuli Kurniawati
ORCID: 0000-0001-7587-5504
Study design and planning; Critical literature review; Critical review of the manuscript.
Riany Jade Sabrina Toisuta
ORCID: 0009-0008-9316-9281
Preparation and writing of the manuscript; Collecting, analyzing, and interpreting data; Effective participation in research orientation; Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases.
Erlinda Karyadi
ORCID: 0009-0008-5761-7534
Preparation and writing of the manuscript; Collecting, analyzing, and interpreting data; Effective participation in research orientation; Intellectual participation in propaedeutic and/or therapeutic conduct of studied cases.

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