Harnessing PRF and Albumin

The pursuit of skin rejuvenation has become more common across all generations, driving demand for effective and natural treatments. Albumin platelet-rich fibrin (aPRF) is a novel autologous regenerative gel derived from a patient’s own blood. It offers a promising approach to skin rejuvenation by harnessing endogenous proteins and growth factors. 

The process of preparing aPRF begins with centrifugation of whole blood to isolate key components—platelet-rich fibrin (PRF) and human serum albumin (HAS). HSA, the most abundant protein in the body, is subjected to controlled heating to stimulate irreversible denaturation and promote intermolecular bonding, without the use of external additives.¹ The denaturing process allows the protein to unfold, providing a 3-dimensional scaffolding structure for intermolecular bonding with PRF. This thermally denatured albumin is subsequently combined with PRF to form aPRF.² Recent studies suggest that regenerative properties of aPRF stem from the slow release of growth factors in liquid PRF as the albumin gel degrades.³

Established regenerative principles state 3 key components are essential for tissue regeneration:

• A 3D matrix that can support tissue development.⁴
• Cells that can promote tissue formation.⁴
• Bioactive growth factors that enhance cell recruitment and differentiation on the biomaterial surface.⁴

PRF meets all 3 essential components for tissue regeneration. Its fibrin matrix serves as a scaffold for cellular growth, while its cellular content, including leukocytes, macrophages, neutrophils, and platelets, facilitates the attraction and recruitment of regenerative cells to the treatment site. Additionally, the fibrin network acts as a reservoir for growth factors, allowing for sustained release over time.⁴ These combined features make PRF a promising material for regenerative applications. 

Since platelet concentrates were introduced, advancements have aimed to improve growth factor concentration and quality. Compared to other concentrations of growth factors, PRF provides a fibrin mesh that favors a slower release of growth factor. However, the limited stability of the fibrin mesh may hinder its suitability for aesthetic procedures that require greater structural durability.⁴ The discovery of albumin’s structural change during heated denaturing provided a solution. When albumin is heated, it undergoes structural changes that form new hydrogen and disulfide bonds within the enzyme. These modifications promote a more complex 3-dimensional shape and significantly alter its absorption characteristics, resulting in enhanced stability.⁴ Combining PRF with heat-denatured albumin improves the filler’s structure and stability, making it a longer lasting and more effective option for regenerative and aesthetic treatments.

Recently, there has been backlash against filler injections due to increased information and misinformation on social media. Compared to aPRF, non-autologous fillers can cause various side effects including allergic reactions and early or late inflammatory responses such as swelling, irregularities, and nodule formation. 

These complications can result in facial asymmetry and negatively affect overall aesthetic outcomes.⁵ Unlike hyaluronic acid fillers, aPRF does not pose a significant risk for migration or long-term lymphatic obstruction and offers a more replenishing appearance. The regenerative properties of aPRF help boost collagen production. Rather than creating additional structure, aPRF restores natural volume. This is especially useful in patients with thin periorbital skin, who are not candidates for fillers. In addition to volume restoration, aPRF can address discoloration by increasing blood circulation in the treated area. 

OFFICE PROTOCOL

At Kian Aesthetic Institute, the preparation of our aPRF (ezGEL, CosmoFrance) begins with drawing 2 vials of blood from the patient. One vial is centrifuged at 2600 rpm for 7 minutes to separate albumin. The separated albumin is transferred into a heat-resistant syringe for heating at 75°C. At this temperature, albumin denatures, forming a gel-like consistency. Simultaneously, the second vial is centrifuged at 1100 rpm for 5 minutes to isolate PRF. To prevent premature coagulation (as there are no additives), the PRF is stored in a cold bath while the albumin-rich PRF completes its heating process. After 10 to 14 minutes, albumin is removed from the heat block and cooled to room temperature to avoid PRF denaturing upon mixing. The cooled albumin and PRF are combined at a ratio of 3.5 mL albumin to 1.5 mL PRF. The resulting mixture is transferred into 1-mL syringes and ready for injection. 

CLINICAL EVALUATION

A prospective study was conducted at our clinic to evaluate the safety and efficacy of aPRF in correcting moderate-to-severe nasolabial folds.⁶ Fifteen healthy participants over age 22 with clinically assessed moderate nasolabial folds were enrolled. Participants were instructed to refrain from any additional cosmetic treatments to the targeted area throughout the duration of the study. Each participant received an initial aPRF injection, with an optional touch-up at Week 4 and a retreatment at Week 16, based on the patient’s need and at the discretion of the primary investigator. By the end of the study, 48% of participants were rated as “very much improved” and 30.8% as “much improved” compared to baseline, as shown in the Global Aesthetic Improvement Scale (Figure 1). 

Fig. 1: Visual compression of nasolabial folds 20 weeks from baseline (left, baseline; right, Week 20, after three total treatments).

Additionally, participants demonstrated a progressive reduction in wrinkle severity scores over time, indicating sustained aesthetic improvement. No serious treatment-related adverse events were reported during the study, showcasing the effectiveness and safety of aPRF as an autologous filler for improving nasolabial folds. 

THE ART OF REVERSAL

Another clinical protocol with aPRF is in The Art of Reversal®, created by Amy Lynn Birkenstamm, RN, CANS. With the rise of dermal filler use in aesthetic medicine, complications such as overcorrection, migration, or undesired results have increased. Traditional filler reversal techniques rely primarily on hyaluronidase to dissolve undesired hyaluronic acid (HA) filler, often requiring a 2-week waiting period prior to retreatment. This approach, while effective in removing products, frequently leads to loss of natural volume, tissue disruption, and compromised dermal health due to repeated cycles of breakdown and reinjection. Additionally, patients may experience prolonged inflammation, swelling, and dissatisfaction with the temporary aesthetic outcome during the waiting phase. 

The Art of Reversal is a protocol that addresses these limitations by combining precise filler dissolution using hyaluronidase with or without ultrasound, with simultaneous regenerative restoration through aPRF. This dual-action approach enables immediate replenishment of lost volume using the patient’s own biologic material, supporting tissue health and accelerating recovery. 

Through live ultrasound mapping, filler deposits are identified and treated with hyaluronidase. In the same session, aPRF is injected into the reversal zones to initiate collagen production and restore volume naturally, eliminating the need for a waiting period between reversal and retreatment. This is especially useful in the periorbital and perioral regions.

In a retrospective clinical review of 45 patients treated with this technique, outcomes demonstrated significantly improved patient satisfaction, reduced inflammation, shortened recovery time, and visible enhancement in tissue quality. Figure 2 illustrates its application in complex zones such as the periorbital area, lips, and perioral region.⁷

Fig. 2. A patient with undereye filler (>2 years old) causing puffiness and irregularities (top) is treated with 0.8 mL hyaluronidase to dissolve the filler, followed by 2 mL aPRF (ezGEL, CosmoFrance) (bottom, 2 months post-treatment). 

The Art of Reversal represents a shift in aesthetic medicine—redefining reversal as not just a corrective procedure, but a regenerative one that preserves and restores natural beauty. 

PRF + FAT GRAFTING

Another area utilizing PRF is fat grafting. Fat grafting has been widely used as a filler due to its abundance of regenerative multipotent cells, such as adipose-derived stem cells (ADSCs). Once integrated into the host tissue, the graft can secrete a coordinated array of cytokines and growth factors that support tissue regeneration. In fat grafting, a patient’s own fat tissue is used to restore volume in areas with deficits. The success of fat transfer depends partly on the patient, but primarily on the surgical technique used. 

However, even with optimal techniques, fat graft survival remains unpredictable. One current method involves enriching the graft with mesenchymal stem cells. While this approach offers the highest potential for graft survival and integration, it is time-consuming, expensive, and produces variable results.⁸ Using PRF with fat grafting has been shown to be a cost-effective and possibly more effective approach. 

Before the widespread use of PRF, platelet-rich plasma (PRP) was the standard.6 PRP is prepared with additives to prevent coagulation and is spun at a high speed. 

Incorporating PRP into fat grafting preparation may enhance early nutrient delivery at the transplantation site, thereby improving fat graft viability and producing more consistent outcomes. PRP provides a concentrated release of growth factors in a balanced ratio, which stimulates angiogenesis, cellular differentiation, and proliferation. These biological processes contribute to the reconstruction of the extracellular matrix and support the proper 3-dimensional organization of adipocytes. Recent studies have showcased PRP improving fat grafting maintenance and function in patients undergoing plastic reconstructive surgery, potentially through the stimulation of ADSC proliferation.⁹

^{“The Art of Reversal represents a shift in aesthetic medicine—redefining 
reversal as not just a corrective procedure, but a regenerative one that
preserves and restores natural beauty.”}

While PRP was a core development in regenerative medicine, it is now considered obsolete by some, due to its reliance on additives to prevent coagulation and the use of high-speed centrifugation. These additives diminish the autologous nature of PRP.

In contrast, PRF is 100% autologous, as it contains no additives and is spun at a lower speed. This low-speed protocol allows for the spontaneous formation of a fibrin matrix at the injection site. This matrix binds and gradually releases growth factors, promoting collagen synthesis and enhancing tissue regeneration.¹⁰ PRF offers all the clinical benefits of PRP, with the added advantage of a naturally forming scaffold that supports clot formation, sustains growth factor release, and prolongs the presence of stem cells.¹¹ During one study, different groups of mice were treated with PRP plus fat graft, PRF plus fat graft, and normal saline plus fat grafts. Results showed the group with PRF plus fat grafts had an increased tissue retention compared to that of the control group. PRP plus fat graft did not yield statistically significant results. Additionally, the PRF-treated group had a high vascularization compared to the PRP-treated group. Although the PRP-treated group showed a higher vessel density compared to that of the control group, they did not demonstrate enhanced tissue retention.¹²

PRF + BIOSTIMULANTS 

PRF can be used in combination with different biostimulants to boost skin rejuvenation—including one designed to restore volume and replenish areas affected by fat loss (Renuva, MTF Biologics). Once injected, this biostimulant forms a matrix that helps support the body’s natural fat regeneration process. Over the course of 3 to 6 months, this matrix gradually degrades, leaving behind newly generated fat.¹³

In our practice, this biostimulant is combined with PRF to enhance its delivery and regenerative effects. PRF supports fat grafting and promotes tissue healing. When used together, PRF and the biostimulant provide a smoother injection experience and potentially boost overall fat regeneration (Figure 3). 

Fig. 3: A patient is treated with 3 cc biostimulant (Renuva, MTF Biologics) mixed with 2 cc PRF to the midface (left, baseline; right, 6 months post treatment).

Another biostimulant is poly-L-lactic acid (PLLA) (Sculptra, Galderma), a compound that works by stimulating collagen production.¹⁴ PLLA creates a supportive framework within the skin, gradually restoring volume and improving skin texture. Studies have shown that PLLA effectively enhances the skin’s inner structure by promoting new collagen formation.¹⁵

For our clinical use, it is common to combine PLLA with PRF to introduce additional growth factors that may amplify collagen production, further improving skin quality and rejuvenation outcomes. Not only does this boost the quality of treatment, but it also allows for multiple sustained treatments over time. This allows for overall better absorption and layered treatments, for maximum compounded results. 

Fig. 4: A patient receives 3 cc of PLLA (Sculptra, Galderma) mixture per side in the temples and 1.5cc per side in the buccal hollows; the mixture consists of 1 vial of PLLA combined with 3 cc PRF, 5 cc bacteriostatic water (BSW), and 1 cc of 2% lidocaine (left, baseline; right, 1-month post-treatment).

CONCLUSION

Building on this regenerative approach, aPRF demonstrated a strong safety profile and promising efficacy as a regenerative treatment for skin rejuvenation across diverse age groups. As the demand for natural, minimally invasive aesthetic procedures continues to grow, autologous treatments offer a compelling alternative to synthetic dermal fillers. The evolving role of PRF in aesthetic medicine highlights a shift toward regenerative, biologically driven approaches that go beyond surface correction to promote deep tissue restoration. Whether paired with autologous fat grafts or certain biostimulants, PRF enhances the efficacy of these treatments by providing a matrix of growth factors that stimulate cellular repair, support collagen synthesis, improve graft survival and volumization, and support long-term skin rejuvenation and tissue integrity. 

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10. Tuan TL, Song A, Chang S, et al. In vitro fibroplasia: matrix contraction, cell growth, and collagen production of fibroblasts cultured in fibrin gels. Exp Cell Res. 1996;223(1):127-134. https://doi.org/10.1006/excr.1996.0065

11. Utomo DN, Jusuf AA, Rizki A, et al. Implantation of platelet-rich fibrin and allogenic mesenchymal stem cells facilitate the healing of muscle injury: an experimental study on animals. Int J Surg Open. 2018;11:4-9. https://doi.org/10.1016/j.ijso.2018.03.001

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13. The safe and effective way to replace volume loss. Renuva. https://www.myrenuva.com/. Accessed September 11, 2025. 

14. Sculptra®: skin that feels like you again. Sculptra. https://www.sculptrausa.com/. Accessed July 18, 2025. 

15. Goldberg DJ, Berlin AL, Phelps R, et al. Single-arm study for the characterization of human tissue response to injectable poly-L-lactic acid. Dermatol Surg. 2013;39(6):915-922. https://doi.org/10.1111/dsu.12164