PRP vs Fluid-PRF for Skin Regeneration: How Preparation Influences Fibroblast Activity and Collagen Synthesis
Wang X, Yang Y, Zhang Y, Miron RJ. Fluid platelet-rich fibrin stimulates greater dermal skin fibroblast cell migration, proliferation, and collagen synthesis when compared to platelet-rich plasma. Journal of Cosmetic Dermatology. 2019;18(6):2004-2010. doi:10.1111/jocd.12955.
Introduction
Platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) are both autologous blood-derived preparations used in regenerative and aesthetic medicine, but they are not biologically identical. Their differences begin with how the blood is processed: conventional PRP is prepared with an anticoagulant and higher centrifugal forces, whereas fluid-PRF is produced without anticoagulant using low-speed centrifugation, allowing fibrin formation to occur after preparation.
Wang et al. compared these two preparations in human dermal fibroblasts to determine whether their different processing methods translate into different regenerative responses. The study assessed cell viability, migration, spreading, proliferation, expression of key dermal and extracellular-matrix markers, and collagen type I synthesis, providing a mechanistic comparison of PRP and fluid-PRF rather than a clinical treatment trial.
Key Preparation Differences Between PRP and Fluid-PRF
Table 1. PRP versus fluid-PRF preparation and dermal biological differences These preparation differences are more than technical variations: they shape the composition and fibrin-forming behaviour of each preparation. The next section examines how those differences may influence dermal fibroblast activity and extracellular matrix signalling. Dermal Biology: Why PRP and Fluid-PRF Behave Differently Although both are autologous platelet concentrates, PRP and fluid-PRF differ substantially in how they are prepared and how they interact with dermal fibroblasts.
In Wang et al., PRP was prepared from anticoagulated blood using higher-speed, two-step centrifugation, producing a liquid platelet-rich plasma fraction. Fluid-PRF was prepared without anticoagulant using low-speed centrifugation at 60 g for 3 minutes. The resulting preparation remains injectable for approximately 15 minutes before fibrin polymerisation occurs.
This fibrin-forming environment is an important biological distinction. PRF retains platelets, leukocytes and growth factors within a developing fibrin network, which may allow more sustained release of regenerative mediators during tissue remodelling.
Figure 1. PRP versus fluid-PRF preparation and dermal biological differences
Both preparations supported high fibroblast viability, but fluid-PRF produced stronger regenerative responses. Fibroblast migration increased to approximately 200% of control with PRP and to more than 300% with fluid-PRF. Fluid-PRF also produced greater fibroblast proliferation by day 5 and higher expression of TGF-β, collagen type I and fibronectin-related genes.
Collagen type I staining was also highest in the fluid-PRF group, supporting a stronger extracellular matrix response under the in-vitro conditions studied. These biological differences provide the rationale for the study’s subsequent comparison of fibroblast migration, proliferation, gene expression and collagen synthesis.
Study Model and Experimental Technique To test these biological differences directly, normal facial skin was obtained from three human donors undergoing cleft lip repair. Dermal fibroblasts were isolated from skin above the lip and cultured for the experimental comparisons. Cells from passages 3–7 were used.
PRP and fluid-PRF were incubated for three days to generate conditioned media. Human dermal fibroblasts were then cultured with 20% PRP-conditioned media, 20% fluid-PRF-conditioned media or control media. The investigators assessed viability, migration, cell spreading, proliferation, expression of PDGF, TGF-β, collagen type I alpha 1 (COL1A1) and fibronectin (FN1), and collagen type I staining.
Figure 2. Human dermal fibroblast migration after 24 hours.
Cell Migration and Poliferation
Fibroblast migration is an early component of wound repair and tissue remodelling. In the transwell assay, PRP increased migration to approximately 200% of control, while fluid-PRF increased migration to more than 300% of control and was significantly higher than PRP.
Both preparations also promoted fibroblast spreading during the early observation period. For proliferation, there was no significant difference between groups at day 1. By days 3 and 5, both PRP and fluid-PRF significantly increased fibroblast proliferation, with fluid-PRF showing the highest cell numbers at day 5.
Figure 3. Effects of PRP and fluid‐PRF on the morphology and proliferation of human skin fibroblasts (A) Cell morphology at 2, 4, 8, and 24 hours; (B) average surface planar area of cells (C) Cell proliferation at 1, 3, and 5 days
Regenerative Signalling and Extracellular Matrix Gene Expression Next, gene expression associated with regenerative signalling and extracellular matrix production was assessed. Both PRP and fluid-PRF increased PDGF and TGF-β expression. Fluid-PRF produced the highest PDGF mRNA levels at day 3 and the highest TGF-β mRNA levels at both days 3 and 7.
For extracellular matrix markers, PRP significantly increased COL1A1 expression at day 7 compared with control. Fluid-PRF significantly increased COL1A1 at both days 3 and 7 compared with the other groups. Fibronectin expression also increased with both preparations, with fluid-PRF producing the highest levels.
Figure 4. Expression of regeneration‐ related and ECM‐related genes of gingival fibroblasts cultured with PRP and fluid‐PRF at 3 and 7 days
Collagen Type I Synthesis To evaluate matrix production directly, the authors performed collagen type I immunofluorescent staining after seven days. PRP produced a significant increase in collagen type I staining compared with control, while fluid-PRF produced an approximately twofold increase and was significantly higher than both control and PRP.
This finding is particularly relevant because type I collagen is a major structural component of the dermis. However, an in-vitro increase in collagen staining should be interpreted as a mechanistic finding, not as proof of a predictable clinical increase in dermal thickness or visible rejuvenation.
Figure 5. Immunofluorescent collagen type 1 (COL1) staining of skin fibroblasts cultured with PRP and fluid‐PRF at 7 days
Clinical Interpretation and Limitations Wang et al. demonstrate that PRP and fluid-PRF are biologically distinct preparations. Under the conditions tested, fluid-PRF produced greater fibroblast migration, higher proliferation at day 5, stronger regenerative and extracellular-matrix gene expression, and greater collagen type I synthesis than PRP. Both preparations maintained >95% fibroblast viability, with no evidence of cytotoxicity in vitro.
These findings remain pre-clinical. The study used fibroblasts from only three donors and did not assess facial injection outcomes, durability, patient satisfaction or clinical adverse events. The results are also specific to the preparation protocols studied, so they do not establish clinical superiority of fluid-PRF over PRP for facial rejuvenation.
Conclusion In conclusion, there is mechanistic evidence that fluid-PRF produces a stronger regenerative response in human dermal fibroblasts than conventional PRP under the experimental conditions studied. Fluid-PRF enhanced fibroblast migration and later proliferation, increased expression of PDGF, TGF-β, COL1A1 and fibronectin, and produced the greatest collagen type I staining.
The broader implication is that anticoagulant use, centrifugation force, centrifugation duration and fibrin formation can materially change the biological behaviour of platelet concentrates. These findings support viewing fluid-PRF as a distinct autologous biomaterial, while clinical studies are still required to determine whether its in-vitro advantages translate into superior aesthetic outcomes. Reference: Wang X, Yang Y, Zhang Y, Miron RJ. Fluid platelet-rich fibrin stimulates greater dermal skin fibroblast cell migration, proliferation, and collagen synthesis when compared to platelet-rich plasma. Journal of Cosmetic Dermatology. 2019;18(6):2004-2010. doi:10.1111/jocd.12955.
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