The goal of this clinical trial is to learn if exosomes from human umbilical cord and bone marrow can improve atrophic acne scars when used after fractional CO₂ laser treatment in adults.

The main questions it aims to answer are:

• Do exosomes improve acne scars more than standard treatment alone?
• Are exosomes safe when used after laser treatment? Researchers will compare one side of the face treated with exosomes to the other side treated with a control solution (hyaluronic acid) to see if exosomes improve scar appearance and skin texture.

Participants will:

• Receive two sessions of fractional CO₂ laser treatment, 4 weeks apart
• Have exosomes applied to one side of the face and a control solution applied to the other side after each treatment
• Continue applying the assigned solution at home for 2 days after each session
• Attend follow-up visits to assess scar improvement, skin texture, healing time, and side effects Researchers will measure changes in acne scars using clinical scoring systems, skin imaging, and patient satisfaction. Safety will also be monitored by recording any side effects such as redness, swelling, or acne flare.

This study may help determine whether exosomes can improve the results of laser treatment for acne scars without increasing side effects

Atrophic acne scars are a common sequela of acne vulgaris and are associated with significant psychosocial burden, including reduced self-esteem and impaired quality of life. Despite the availability of multiple treatment modalities, complete resolution remains challenging. Among current options, ablative fractional carbon dioxide (CO₂) laser is considered one of the most effective approaches due to its ability to induce dermal remodeling and stimulate collagen production. However, its clinical use is limited by downtime, risk of adverse effects such as post-inflammatory hyperpigmentation, and the need for multiple treatment sessions.

Exosomes derived from mesenchymal stem cells (MSCs) have recently emerged as a promising adjunctive therapy in dermatology. These nano-sized extracellular vesicles contain bioactive molecules, including growth factors, cytokines, and nucleic acids, which play a key role in intercellular communication and tissue regeneration. Preclinical studies have demonstrated that MSC-derived exosomes enhance fibroblast proliferation, promote collagen synthesis, and modulate inflammatory responses by shifting macrophage polarization toward an anti-inflammatory phenotype. These mechanisms suggest that exosomes may improve wound healing and optimize outcomes following laser-based treatments.

This study is a randomized, double-blind, split-face, controlled prospective clinical trial designed to evaluate the efficacy and safety of human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-exo) and bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-exo) as an adjunct to ablative fractional CO₂ laser in the treatment of atrophic acne scars. The study was conducted at the Dermatology and Skin Aesthetics Department, University Medical Center, Ho Chi Minh City, Vietnam.

A total of 22 adult participants with bilateral atrophic acne scars were enrolled. All participants underwent two sessions of ablative fractional CO₂ laser treatment at 4-week intervals. Immediately after each laser session, one side of the face was treated with a topical exosome solution (containing hUC-MSC-exo and BM-MSC-exo), while the contralateral side received a hyaluronic acid-based control solution. Participants continued applying the assigned topical treatment twice daily for two additional days following each session. Allocation of treatment sides was randomized, and both participants and outcome assessors were blinded to group assignment.

Clinical assessments were performed at baseline (T0), 4 weeks after the first session (T1), and 4 weeks after the second session (T2). The primary outcome was the percentage improvement in the Echelle d'Évaluation Clinique des Cicatrices d'Acné (ECCA) score from baseline to T2. Secondary outcomes included changes in ECCA scores by scar subtype (ice-pick, boxcar, and rolling scars), skin texture improvement measured using the VISIA® imaging system, Investigator's Global Assessment (IGA), patient satisfaction, and healing-related parameters.

Safety evaluation included monitoring and recording all adverse events, such as erythema, edema, pain, crusting, post-inflammatory hyperpigmentation, acne flare, infection, and scarring. The severity and duration of these events were compared between exosomes and control sides.

This study aims to determine whether the addition of hUC-MSC-exo and BM-MSC-exo can enhance the clinical efficacy of fractional CO₂ laser in improving atrophic acne scars while maintaining a favorable safety profile. The findings may provide evidence for a novel adjunctive approach to optimize acne scar treatment outcomes.

Inclusion Criteria:

• Adults aged ≥18 years
• Presence of bilateral atrophic acne scars on the face
• Eligible for ablative fractional CO₂ laser treatment

Exclusion Criteria:

• - Pregnancy or breastfeeding
• History of keloid or hypertrophic scarring
• Active acne inflammation or facial infection
• Use of oral isotretinoin within the past 6 months
• Recent facial procedures within the past 6 months, including ablative laser, radiofrequency microneedling, dermabrasion, or medium-to-deep chemical peel
• Use of systemic corticosteroids or non-steroidal anti-inflammatory drugs affecting wound healing

Individual participant data will not be shared due to privacy and confidentiality concerns and institutional data protection policies.

This is a double-blind study. Participants, treating physicians (care providers), and outcome assessors are blinded to treatment allocation. The exosome solution and control solution are prepared in identical containers with identical appearance and texture and are labeled only as "Right" or "Left" according to a computer-generated randomization sequence. This ensures that neither participants nor investigators can distinguish between treatments. Outcome assessments are performed by independent blinded evaluators.