The efficacy, safety, and application of platelet-poor plasma gel as an autologous dermal filler for esthetic enhancements and facial rejuvenation – A pilot study

INTRODUCTION

Facial rejuvenation procedures have become increasingly popular in recent years, driven by a growing desire for esthetic enhancement and the correction of skin imperfections. As the demand for non-surgical interventions rises, practitioners are continuously seeking effective and safe options that cater to diverse patient needs. Among various modalities, autologous dermal fillers have gained prominence due to their biocompatibility, cost-effectiveness, and lower risk of adverse hypersensitivity reactions. Notably, platelet-poor plasma gel (PPP gel) has emerged as a valuable alternative, offering a cost-effective solution for facial augmentation and rejuvenation.^[1]

The history of dermal fillers dates back to the early 20^th century with materials such as paraffin and silicone, which, despite their innovation, often caused complications. The introduction of collagen-based fillers in the 1980s improved biocompatibility, but the demand for longevity led to the rise of hyaluronic acid (HA) fillers in the late 1990s, valued for their safety and reversibility. The shift toward autologous fillers, such as PPP gel, reflects the field’s evolution toward natural approaches.^[2] Activated by thermal treatment, PPP gel forms a stable, fibrin-rich material with enhanced consistency and volume, offering a promising alternative in regenerative esthetics.^[3]

The aim of this study is to evaluate the efficacy and safety profile of PPP gel in facial rejuvenation along with patients’ satisfaction. By utilizing the global esthetic improvement scale (GAIS) and assessing patient satisfaction scores with the Likert scale, we aim to provide a comprehensive understanding of the psychological and esthetic benefits of this innovative treatment.

MATERIALS AND METHODS

A total of 30 patients were enrolled in our study as per the convenience sampling method. Patients between 20 and 65 years of age with facial volume loss, scars, or requiring facial rejuvenation were included in our study excluding patients with unrealistic expectations, chronic illnesses, and who have undergone any other cosmetic procedures within the preceding two months. All patients were subjected to full history taking and dermatological examination.

Ethics

Approval by the Institute Ethical Committee, Pacific Medical College and Hospital, Udaipur was obtained before the commencement of the study.

Date of issuance: June 01, 2023.

Reference no.: PMU/PMCH/IEC/PG/2023/244

Informed and written consent for the study and procedure was explained. Consent for use of their clinical photographs for publishing purposes was obtained from all patients.

PPP gel preparation

Ten milliliters of the patient’s blood is drawn and mixed with 1 mL anticoagulant acid citrate dextrose. A two-staged centrifuging is performed using a Digital 8R Dermafuge Centrifuge device (Derma India, Chennai). It is rotated at 2400 rotations per minute (RPM) for 5 min in the centrifuge machine. The plasma solution is withdrawn and centrifuged again at 2600 RPM for 10 min. The upper part (upper 2/3^rd) that is platelet-poor plasma (PPP) is withdrawn in a tuberculin syringe or 2 mL syringe as per requirement and the lower part (lower 1/3^rd) that is Platelet-rich plasma (PRP) is withdrawn in tuberculin/insulin (1 mL) syringes (which can be used for rejuvenation if required). Calcium gluconate (activator) is added to the PPP in the proportion of 0.1 mL/1 mL of PPP. It is incubated in hot water [Figure 1] (heated in a metal container/hot water bath) at 60°C–100°C (gradually reducing to 98°C) for 3–5 min and then in a cold water bath in a metal container with initial temperature 7°C and gradually increasing to 10°C for 10 min. The temperatures are measured by a digital thermometer. The viscous gel obtained is the PPP gel, a bio-filler [Figure 2].

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Figure 1:

Platelet-poor plasma gel preparation by thermal treatment with monitoring of temperature using a digital thermometer.

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Figure 2:

Black arrow shows the prepared platelet-poor plasma gel.

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Treatment procedure

After informed and written consent, topical 2.5% lidocaine plus 2.5% prilocaine anesthetic cream is applied over the patient’s face on the areas to be treated for 45 min (if required). Ten milliliters of the patient’s blood is drawn and mixed with 1 mL anticoagulant acid citrate dextrose. PPP gel is prepared as mentioned above. After cleaning the topical anesthetic cream, PRP is injected at multiple points over the forehead, cheeks, and chin through insulin syringes (This step is only done if required for rejuvenation to prevent wastage of PRP prepared). Then, PPP gel filler is injected in the deep dermis with tuberculin syringes with 25 G/27 G needle or 50 mm/38 mm blunt tip microcannula [Figure 3a and b] as per requirement at the desired site with appropriate needles and precautions. It is injected linearly along the desired site depositing the bio-filler while withdrawing the needle for lip augmentation (linear threading technique). Injections are placed away from blood vessels with facial anatomy kept in mind. The sites are gently massaged to allow uniform distribution of the injected plasma gel to maintain the contour of the surrounding tissues.

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Figure 3:

(a) Platelet-poor plasma gel prepared after activation and thermal treatment in tuberculin syringes. (b) Microcannula of 50 mm attached to tuberculin syringe.

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RESULTS

A total of 30 patients were included in our study with a male-to-female ratio of 1:1.6. The treated conditions included twelve patients for under-eye rejuvenation, eight patients with acne scars, four patients for chin augmentation, two patients each for lip augmentation and post-varicella scars, and one patient each with chemical scarring and facial hemiatrophy.

GAIS score point reduction in pre- and post-treatment scores are summarized in Graph 1. The majority of the patients had a two- to three-point reduction in GAIS. The conditions that exhibited the most significant four-point GAIS reduction post-treatment were facial hemiatrophy [Figure 4], lip augmentation [Figure 5], and chin augmentation [Figure 6]. Few cases of under-eye rejuvenation [Figures 7 and 8] and chemical scarring [Figure 9] also demonstrated substantial improvements with GAIS reductions of three to four points. The mean GAIS score significantly improved from 4.4 (pre-treatment) to 2 (post-treatment), reflecting an overall improvement of 54%. Effect size according to Cohen’s d was approximately 1.8 indicating a large treatment effect. The inter-rater agreement calculated using Cohen’s kappa shows that the chance-corrected agreement was 0.8, meaning their agreement was almost perfect.

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Graph 1:

Summarizes the global esthetic improvement scale (GAIS) point reduction percentage in study participants. X-axis shows the number of patients and Y-axis shows GAIS point reduction.

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Figure 4:

A 23-year-old female with facial hemiatrophy due to morphea (a) pre-treatment and (b) post-treatment.

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Figure 5:

A 32-year-old female for lip augmentation (a) pre-treatment and (b) post-treatment.

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Figure 6:

A 26-year-old female for chin augmentation (a) pre-treatment and (b) post-treatment.

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Figure 7:

A 37-year-old female with tear trough deformity and crow’s feet (a) pre-treatment and (b) post-treatment.

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Figure 8:

A 34-year-old female with tear trough deformity (a) pre-treatment and (b) post-treatment.

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Figure 9:

A 20-year-old male with chemical burn scar due to choona application (a) pre-treatment and (b) post-treatment.

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The mean patient satisfaction score was 3.52/5 with an overall satisfaction rate of 70.4%. The highest satisfaction rates were observed in patients who underwent chin augmentation, under-eye rejuvenation, facial hemiatrophy correction, and lip augmentation.

Wilcoxon signed-rank test results demonstrated a statistically significant difference between pre- and post-treatment GAIS scores where Wilcoxon test statistic (W) was 465.0 and the calculated p-value was ~1.86 × 10⁻⁹, that is <0.05, which strongly suggests autologous PPP gel to be efficacious.

Follow-up was done for a duration of two months post-procedure. There was a gradually progressing decrease in the filling and volumetric effect of the autologous PPP gel and 53.33% of the patients sustained the same overall response until the end of two months of follow-up duration. The majority of the patients with acne scars [Figure 10] and post-varicella scars [Figure 11] had a reduction in effect after one month of treatment. Patients who underwent under-eye rejuvenation, lip and chin augmentation, and facial hemiatrophy correction showed better maintenance of the overall results. Three patients – two cases of acne scars and one case of post-varicella scars were lost to follow-up probably due to the low overall improvement seen post-procedure.

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Figure 10:

A 27-year-old male with acne scars (a) pre-treatment and (b) post treatment.

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Figure 11:

A 28-year-old male with post post-varicella scars (a) pre-treatment and (b) post treatment.

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The most commonly observed side effect was transient erythema [Figure 12], followed by injection site edema [Figure 13], pain, and burning sensation. These side effects were self-limiting which resolved within a few hours post-procedure. No severe adverse events or complications were reported during the two-month follow-up period. Almost all patients experienced injection site pain and erythema while the least common side effect noted was asymmetry due to overfilling on one side in an under-eye rejuvenation patient [Figure 14], which was corrected by manual manipulation. There were no reported complications or adverse effects such as vascular occlusion, ecchymosis, infection, nodules, foreign body granuloma formation, or tissue necrosis.

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Figure 12:

Transient erythema immediately post-procedure.

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Figure 13:

Erythema with localized edema immediately post-procedure.

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Figure 14:

Asymmetry due to overfilling of platelet-poor plasma gel over right side (R) in comparison to the left side (L). Black arrows shown point the area overfilled.

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DISCUSSION

The evolution of dermal fillers has progressed significantly over the past century. In the early 20^th century, paraffin and liquid silicone were among the first substances used for facial augmentation. By the 1960s, collagen-based fillers derived from animal sources (bovine collagen) became popular, though they had limitations in longevity and potential allergic reactions. The 1990s saw the introduction of HA fillers, which were biocompatible and naturally integrated into the skin and are still being routinely used worldwide. The 2000s brought longer-lasting fillers, including cross-linked HA, calcium hydroxyapatite, and poly-L-lactic acid, offering enhanced durability and volume restoration. In the 2010s, the focus shifted to customization and non-surgical facelifts followed by advancements in fat transfer and biostimulatory fillers. The 2020s have been marked by the rise of longer-lasting HA fillers, PRP integration, and personalized treatments, along with the emergence of biofillers utilizing PPP, representing the latest innovation in regenerative esthetics.^[2]

Biofillers being natural dermal fillers can be classified into synthetically prepared HA fillers, collagen-based fillers, and those derived from natural substances or autologous fillers. Autologous dermal fillers are products that are derived from the patient’s own tissues, primarily used for facial volume restoration and skin rejuvenation. Unlike synthetic fillers, these fillers utilize materials such as fat or blood components taken from the patient, ensuring high biocompatibility and minimizing the risk of allergic reactions. Common types of blood-derived fillers such as PRP, PPP or platelet-rich fibrin harness the regenerative properties of growth factors in the blood. The use of autologous materials allows for natural-looking results while promoting healing and stimulating collagen production, making them a popular choice in esthetic medicine.^[4]

PPP although contains a lower concentration of platelets, is composed of 90% water, contains essential proteins (albumin, fibrinogen, and immunoglobulins), electrolytes (sodium, potassium, and calcium), gases (oxygen and carbon dioxide), essential nutrients (glucose, amino acids, and lipids), and hormones. Key growth factors such as transforming growth factor-β, fibroblast growth factors, platelet-derived growth factors, epidermal growth factors, and insulin-like growth factors in PPP play a crucial role in volumizing and rejuvenation. In addition, hepatocyte growth factor enhances tissue healing, and interleukins regulate inflammation and tissue recovery making PPP a valuable tool in regenerative esthetics.^[5]

Preparation of PPP using a double spin method in our study was done considering the rotor radius of our centrifuge machine. Activation of the prepared PPP by adding a clotting cascade activator such as calcium gluconate, calcium chloride, or thrombin, followed by thermal treatment, gives rise to the formation of a gelatinous material, PPP gel [Figure 1]. The thermal treatment can either be done in a hot water bath with a thermometer or an incubator fixed at the advised temperature. The duration of the heating process is directly proportional to the viscosity or the G prime of the PPP gel. That is, the more the duration, the higher the G prime.^[6]

The primary mechanism of action for PPP gel involves volumization and stimulation of collagen production. On injection, PPP gel occupies space beneath the skin, filling in lines and hollows while simultaneously triggering a biological response that promotes the body’s own collagen synthesis due to fibrin bundles that provide a scaffold for platelets trapping them in the treatment area to serve as a source for sustained release of growth factors over time.^[3,6] The gel gets absorbed gradually by the body over a period of time making it a temporary option for a natural volumizing effect.

PPP gel offers multiple advantages in esthetic treatments providing a natural volumizing effect similar to that of synthetic HA biofillers. As an autologous, biocompatible material, it eliminates the risk of allergic reactions and adverse hypersensitivity reactions. Its ability to stimulate collagen production enhances skin rejuvenation along with a long-term structural and textural improvements. In addition, PPP gel is well-tolerated, with minimal downtime, making it an effective alternative to traditional dermal fillers. Furthermore, its cost-effectiveness reduces the need for expensive synthetic biofiller, offering a sustainable and economical solution for people seeking esthetic enhancements.^[1,3]

While biofillers are generally considered safe, it is crucial to acknowledge potential side effects and adverse reactions. Commonly reported side effects include transient erythema, localized edema, bruising, pain, and burning sensation at the injection site, which are typically mild and temporary. Although, there were no reports of any serious complications in this study, complications such as vascular occlusion and allergic reactions have been documented and require immediate attention.^[7] Practitioners with a high level of expertise and training have significantly reduced the incidence of these complications. Awareness and appropriate management of these risks are vital for ensuring patient safety and satisfaction. By prioritizing thorough training and patient education, practitioners can help mitigate risks leading to a more positive overall experience for patients considering PPP gel.

PPP gel biofillers offer several advantages primarily due to their easy accessibility, biocompatibility, and cost-effectiveness. However, it is of utmost importance to understand that they are non-dissolvable in contrast to HA fillers that can be lysed with hyaluronidase and provide a better safety profile for serious complications.^[8]

In comparison, HA fillers are often preferred over PPP gel due to their immediate volumizing effect, predictable results, and longer-lasting outcomes. HA fillers offer instant correction with reversible outcomes, making them a safer and more versatile option in esthetic treatments. In addition, HA fillers have Food and Drug Administration approval and extensive clinical research backing their efficacy and safety.^[8]

The increasing societal emphasis on idealized beauty standards has placed significant pressure on the current generation to conform to specific esthetic norms, driving a growing demand for esthetic procedures as individuals seek to enhance their appearance and align with these expectations. Research indicates that improvements in physical appearance can lead to enhanced self-esteem and quality of life. Patients frequently report increased confidence and greater social engagement following treatment.^[9] The patient satisfaction scores in this study illustrate this trend, highlighting the importance of addressing both the physical and emotional aspects of dermatological care.

As the field of esthetic medicine evolves, ongoing research into biofillers continues to yield innovative formulations. For example, hybrid fillers that combine different types of biofillers are being explored to enhance efficacy and longevity.^[10] The versatility of autologous dermal fillers and their application across various dermatological and surgical contexts are yet to be explored. Future studies may explore the potential use of PPP gel and other biofillers in reconstructive surgery, post-trauma repair, and other medical applications beyond esthetic enhancements. Further researches and explorations in near future will likely lead to innovative formulations and expanded uses, reinforcing the significance of biofillers in both esthetic and therapeutic settings.

CONCLUSION

Autologous PPP gel proved to be an effective, well-tolerated, and economical simple clinic procedure for facial rejuvenation and esthetic enhancements, demonstrating significant improvements in patient outcomes. The procedure was associated with high satisfaction rates and a favorable safety profile. Although the maintenance period of plasma gel is relatively short, initial results are favorable and encouraging.