Safety and efficacy of injectable platelet-rich fibrin with fractional carbon dioxide versus fractional carbon dioxide per se in post-acne scars – A split-face study

INTRODUCTION

Acne vulgaris is a persistent inflammatory condition affecting the pilosebaceous unit.¹ Scarring is common sequelae of Grade 3 and 4 acne. This is more likely to result from delayed treatment since the length of inflammation is directly related to the production of scars.¹ There are several types of acne scars, including box, rolling, and ice pick scars. Injectable platelet-rich fibrin (iPRF), a second-generation platelet concentrate, has been created to improve growth factor release and eliminate anticoagulants due to concerns about hypersensitivity reactions.² Fibroblast migration is noticeably greater in fluid platelet-rich fibrin (PRF) than in PRP. Significantly higher cell proliferation and higher amounts of fibronectin messenger RNA (mRNA), transforming growth factor-beta, and collagen 1 are linked to fluid PRF, which increases the stimulation of collagen production.³

iPRF is an entirely autologous substance that aids in healing and regeneration by including cytokines, leukocytes, and growth factors. It uses a straightforward process that only needs one centrifugation stage and is reasonably priced.⁴ One of iPRF’s drawbacks is that it can be used quickly because PRF’s structural integrity changes over time. One of iPRF’s drawbacks is its rapid consumption, which occurs because PRF’s structural integrity varies with time. Because of the risk of bacterial contamination, PRF storage is challenging. Because it is an autologous product, there is not much PRF and it cannot be used over wide areas.⁴ PRF is used to treat a variety of ailments, including acne scars, androgenetic alopecia (in which case an injectable form is employed), face rejuvenation, and ulcers that do not heal from various causes including arterial, venous post-surgery, trophic and neuropathic (leprous/diabetic), and chronic wounds of any cause.⁵

The safety and effectiveness of fractional ablative carbon dioxide (CO₂) lasers in treating scars from various etiologies, including acne scars, have long been established. Procollagen, dermal elastin, heat shock protein, and other materials involved in wound remodeling can accumulate in the micropores created by the fractional CO₂ laser (FCL), ultimately resulting in scar remodeling that changes in texture and shape.⁶

We hereby compare the safety and efficacy of the combination of FCL with iPRF and FCL alone in post-acne atrophic scars.

MATERIAL AND METHODS

The Department of Dermatology at a tertiary care facility in India carried out this split-face prospective comparison study from August 2024 to March 2025.

The Institutional Ethics Committee gave the study its ethical approval. All of the patients provided their informed permission.

Adult patients (18–50 years old) who came to the hospital’s dermatology outpatient department with Grades 3 and 4 post-acne atrophic scars Goodman and Baron post acne scarring score [Table 1a and b]^7,8; these are reference for Table 1a and 1b on their faces and who agreed to take part in the study were recruited.

Patients who did not give consent, those with platelet dysfunction, hemoglobin <10 g/dL, hematologic malignancies, active infections, pregnant and lactating women, keloidal tendency, history of intake of oral nonsteroidal anti-inflammatory drugs in the past 2 days, currently on corticosteroids or anticoagulants, oral isotretinoin in the past 2 months or topical tretinoin in the past 24 h, or had undergone facial procedures in the past 2 months were excluded.

Forty adult patients (18–50 years) were included in the study. Five patients were lost to follow-up (four patients after one sitting and one patient after two sittings). High-quality pictures of the face’s two sides were captured. Severity scoring [Table 2] was done at baseline. Both cheeks were cleaned with cleanser, after which a eutectic mixture of local anesthesia (lignocaine 7% and tetracaine 7%) was administered under occlusion to the impacted area for 30 min. The affected area was cleaned with normal saline and protective eyewear was given. FCL was done (RF-excited FCL) keeping uniform laser parameters (power 12W, duration 1.5 ms, interval 1.0 ms, and distance 0.8 mm). 10 mL of blood was drawn from the antecubital fossa of the patients in a PET tube and centrifuged at 700 rpm for 3 min. From this, 1–2 mL iPRF was prepared. iPRF was prepared using the following technique [Figure 1].

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Figure 1:

Preparation of injectable platelet-rich fibrin (iPRF).

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iPRF was injected intradermally (0.25 × 6 mm insulin syringe with 31G needle) using a multi-puncture technique on the right cheek within 10 min so as to prevent coagulation within the syringe. Two units were injected at the base of the scars and in the normal skin, two units were injected spaced 1 cm apart led to the formation of superficial blebs. Post-procedure ice pack application was done followed by the application of a moisturizer and physical sunscreen. Four sittings were done at an interval of 1 month. Severity scoring [Table 2] was done at each sitting and 2 months after the last sitting. Patients were instructed to use moderate face wash cleaners, a bland emollient at night, and physical sunscreen throughout the day.

Following each session, patients were monitored for 72 h to evaluate any procedure-related side-of-the-facial adverse effects (pain, edema, and erythema) using a Visual Analog Scale with a range of 0–10, where 10 is the most severe of the three requirements for each facial side.

RESULTS

Forty patients were part of the study. Five patients were lost to follow-up (four patients after one sitting and one patient after two sittings). A total of 35 patients, 23 men (66%) and 12 women (34%), completed the study [Figure 2]. The most common age group included in the study was that of 20– 30 years (54%), 6 (17%) were under 20 years of age, and ten (29%) were older than 30 years [Figure 3]. The duration of acne scars was <2 years in 25 participants (71.42%), while it was >2 years in 10 participants (28.57%). 17 (48.57%) patients had Fitzpatrick skin phototype 4, 2 participants (5.71%) had phototype II, 12 participants (34.28%) had phototype III, and 4 participants (11.42%) had phototype V. The mean baseline GB quantitative score on the right side was 11.96 ± 3.56 and on the left side was 11.31 ± 3.44 (P = 0.4568) [Figures 4 and 5, Table 2]. The mean score on the 5^th visit on the right side was 7.28 ± 2.89 and the mean score on the left side was 8.93 ± 3.28 (P = 0.0363) [Table 2]. The mean baseline GB quantitative score on the right side was 11.96 ± 3.56 and the mean score at the 5^th visit was 7.28 ± 2.89 (P < 0.0001) [Table 2]. On the left side, the mean baseline score was 11.31 ± 3.44 and the mean score at the 5^th visit was 8.93 ± 3.28 (P = 0.0064) [Table 2]. The mean difference after five visits on the right side was 4.59375 ± 1.27 and on the left side was 2.4375 ± 0.966 (P < 0.0001). Following each session, each patient was evaluated for subjective symptoms (such as pain, edema, and erythema) in the treated areas using the Visual Analog Scale 72 h later. As mentioned in Table 3, the differences between erythema and edema were statistically significant on the second visit between the right side (6.56 ± 0.84, 6.77 ± 0.86, respectively) and left side (5.10 ± 0.88, 5.06 ± 0.90, respectively) with P < 0.0001. There was also a statistically significant difference in the edema on the third visit between the right (6.46 ± 0.90) and left side (5.12 ± 1.04) with P < 0.0001 [Table 3].

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Figure 2:

Gender distribution.

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Figure 3:

Age distribution.

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Figure 4:

Goodman and Baron quantitative global scarring grading scale upper: Before (7), After (5) Right side, Fractional CO2 laser (FCL) + injectable platelet-rich fibrin Lower: Before (9), After (8), Left side FCL alone.

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Figure 5:

Goodman and Baron quantitative global scarring grading scale upper: Before (14) After (8) Right side. Fractional CO2 laser (FCL) + injectable platelet-rich fibrin Lower: Before (11) After (10), Left side FCL alone.

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DISCUSSION

Acne scars are a difficult dermatological problem that frequently needs to be treated with multiple modalities to provide the desired effects. The majority of the studies that are done to show the improvement of acne scars involving FCL followed by PRP while our study focuses on the effectiveness of FCL with iPRF [Table 4].

Thirty-five of the forty patients who participated in our study completed it, comprising 23 men and 12 women. GB quantitative and qualitative scoring was done at baseline and only quantitative scoring was done at every sitting and at 2 months after the last session. The mean baseline scores of the right side and left side were comparable with no statistical significance while the mean end score on the 5^th visit was statistically significant which showed improvement of the quality of scars on both sides. Ice pick scars showed the least improvement while rolling scars and box scars showed maximum improvement. Scars with lesser duration showed more improvement when compared to the scars that were present for a longer duration. One female with hyperpigmentation on both sides of her face showed marked improvement in pigmentation on the right side compared to the left side [Figure 6].

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Figure 6:

(a) Upper: Right side Fractional CO2 laser (FCL) + injectable platelet-rich fibrin shows improvement in pigmentation on right side compared to the left side (b). (b) Lower: Left side FCL alone.

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Kar et al. studied 30 patients, most of whom were between the ages of 18 and 25.⁹ Duration of scars was <2 years in most patients. Comparing FCL just on the left side of the face with FCL + PRP on the right was the aim of the study. The mean baseline GB quantitative score on the right side was 13.16 ± 6.87; however, the study’s mean final score was 8.66 ± 5.37 (P = 0.001).⁹ The mean final score on the left was 7.33 ± 5.68, while the mean baseline score was 11.93 ± 8.004. These results were similar to our study (P = 0.0001). Similar outcomes were observed on the left side (P = 0.0064), whereas the before and after scores on the right side were statistically significant (P < 0.0001), similar to the results of our study. Both the left and right face’s baseline scores indicated that the scars were equivalent in severity on both sides (P = 0.1242) and that they were comparable at the beginning of therapy (P = 0.4568).

In one study, Lee et al. treated 14 patients with acne scars by performing two FCL treatments on both sides of their faces.¹⁰ They also administered intradermal PRP and saline to one side of this group. According to a quartile rating system, the PRP-treated location showed superior clinical improvement as follows: Improvement score – 0. No improvement; 1. Improvement <25%; 2. Improvement 25–50%; 3. Improvement 51–75%; and 4. Improvement >75%.¹⁰

Shah et al. conducted a split-face study on 30 patients who, on the 5^th day following laser treatment, received intradermal saline and PRP on the one side and FCL on the other.¹¹ Notable progress was shown on both sides of the face; however, the PRP-treated area showed the most improvement, according to the patient and the blinded observer.¹¹

Zhu et al. treated 22 patients with acne scars using topical PRP and an erbium fractional laser.¹² They noted that the PRP-treated patients experienced both clinical improvement and patient satisfaction.¹²

Compared to PRP, iPRF has several benefits. While iPRF preparation time is constrained, PRP is a time-consuming process. In iPRF, an external anticoagulant is not necessary. Growth factors in PRP only last for a short period of time, whereas growth factors are constantly released over time in iPRF. Cellular migration and growth factor mRNA expression are both elevated in iPRF.¹³ iPRF is a low-cost, straightforward process that only needs one centrifugation stage.⁴ In iPRF, the morphology is maintained for at least 10 days, whereas PRP degrades in a week or less.¹³

PRF modules’ structural integrity varies over time. Because of the possibility of bacterial infection and dehydration, PRF cannot be stored. There is not much PRF because it is an autologous product.⁴

CONCLUSION

Combination therapy of FCL with iPRF is a safe and effective modality for post-acne atrophic acne scars. Furthermore, both modalities showed lesser improvement in ice pick and punched-out deep scars. The earlier we are able to treat the post-acne scars, the better the outcome. iPRF is a safe, quick, and easy modality that can be undertaken in both private and public setups. It can be considered for sequential therapy or combination therapy with Trichloroacetic acid chemical reconstruction of skin scars (TCA CROSS), subcision, and microneedling radiofrequency (MNRF).