Interpretation of findings in the clinical context

The findings of this systematic review indicate that Alb-PRF provides notable advantages during the early healing phase, particularly regarding soft-tissue volume maintenance, edema control, and postoperative comfort. Evidence from studies on mandibular third molar surgery and interdental papilla reconstruction consistently supports these short-term benefits [25, 33, 39].

These findings are further supported by clinical investigations. In a split-mouth randomized controlled trial performed during mandibular third molar extractions, Alb-PRF resulted in significantly greater reductions in postoperative pain, edema, and inflammatory biomarker levels compared with L-PRF [39]. Similarly, in interdental papilla reconstruction procedures, Alb-PRF gel injection increased papillary height, although no superiority was observed over conventional PRF in terms of CAL or PPD [33]. In gingival phenotype modification procedures, Alb-PRF application led to a significant increase in GTH at three months compared with connective tissue graft (CTG); however, this difference was not maintained at six months, and KTW remained more stable in the CTG group [22]. Collectively, these findings suggest that Alb-PRF may represent a biologically less invasive adjunct for procedures targeting early soft-tissue healing, although additional high-quality randomized controlled trials are needed to clarify its long-term regenerative potential.

In a prospective two-stage lateral sinus-lifting procedure using Alb-PRF alone, a mean vertical bone gain of 5.07 ± 1.78 mm and a bone density of approximately 323 HU (Hounsfield units) were achieved at 6 months. Although limited in scope, available prospective data suggest that Alb-PRF maintains volumetric stability at the graft site for up to 4–6 months, behaving as a biologically active filler material. However, this conclusion is based on a single uncontrolled study and requires further validation [40].

A recent case report combining Alb-PRF with an alloplastic bone graft for alveolar ridge preservation demonstrated substantial maintenance of bone volume both clinically and radiographically at 6 months, suggesting that Alb-PRF may function as a biological carrier that supports not only soft-tissue repair but also hard-tissue regeneration when used in appropriate combinations. These findings also imply that incorporating Alb-PRF into “sticky bone”–like composites may improve graft stability and reduce postoperative alveolar resorption [41]. In contrast, results in cystic bone cavities remain inconsistent. A three-dimensional volumetric analysis–based randomized controlled trial found no significant additional bone gain at 6 months compared with conventional clot application, though Alb-PRF was safely used without increasing complication rates [42]. Collectively, the evidence suggests that Alb-PRF’s regenerative effect depends on the defect type and surgical indication, and no current data confirm its superiority over classical PRF regarding attachment gain, probing depth reduction, or hard-tissue regeneration [33]. Thus, Alb-PRF should presently be regarded as an adjunctive biological material primarily supporting early soft-tissue healing rather than a primary regenerative agent.

Relationship between biological advantages and clinical outcomes

The thermally stabilized fibrin–albumin matrix supports the prolonged and controlled release of growth factors such as TGF-β1 and PDGF-AA/AB [19,20,21]. In addition to soluble growth factors, emerging evidence suggests that platelet-derived biomaterials may exert part of their biological activity through extracellular vesicles acting as paracrine mediators of immunomodulation and tissue repair [43]. These biological characteristics align well with Alb-PRF’s observed soft-tissue benefits during early healing. Nevertheless, no direct clinical or in vivo evidence currently confirms its immunomodulatory actions—particularly those involving M2 macrophage polarization [23]. The discrepancy between favorable experimental osteogenic signals and the limited clinical hard-tissue outcomes suggests a translational gap between laboratory-based observations and real clinical regenerative performance.

Recent experimental studies suggest that platelet-derived biomaterials can modulate the immune microenvironment by promoting a shift in macrophage phenotype from proinflammatory M1 to regenerative, anti-inflammatory M2, thereby accelerating healing [44]. Narrative syntheses have further contextualized these findings, proposing that such immunomodulatory effects may underlie interindividual variability in clinical outcomes and support phenotype-oriented and personalized periodontal therapy. Therefore, any potential immunoregulatory effects of Alb-PRF should currently be considered biologically plausible but unproven, and confirmation requires further controlled studies. In vitro evidence demonstrates that PRF membranes downregulate IL-1β and IL-6 expression while upregulating M2-associated markers such as arginase-1 and chitinase-like protein-3 (Chi3l3/YM-1), promoting inflammation resolution and tissue repair [45].

Despite its prolonged growth-factor release and enhanced mechanical stability, Alb-PRF lacks key biological prerequisites—such as osteoconductive architecture, space-maintaining capacity, and load-bearing rigidity—required for predictable periodontal hard-tissue regeneration. Specifically, the material does not provide sufficient space-maintaining capacity, osteoconductive architecture, or mechanical rigidity to support sustained bone formation under functional loading. Moreover, the gradual release of growth factors from Alb-PRF appears preferentially optimized for soft-tissue maturation and inflammation resolution rather than for the sustained induction of osteoblast differentiation and mineralized matrix deposition under regenerative conditions. These mechanistic limitations may explain why clinical studies have failed to demonstrate consistent improvements in bone fill, clinical attachment gain, or probing depth reduction when Alb-PRF is used as a stand-alone regenerative material.

Impact of protocol heterogeneity on outcomes

The included studies revealed substantial variation in Alb-PRF heating duration, gel-to-PRF ratio, and centrifugation parameters (Table 3). This methodological heterogeneity reduces the comparability of clinical outcomes and limits the strength of conclusions regarding Alb-PRF’s regenerative potential. According to the GRADE framework (see Supplementary Files X and Y), the overall certainty of evidence was rated as low to moderate due to small sample sizes and protocol heterogeneity.

Table 3 Main methodological parameters reported for Alb-PRF preparation across the included studies

Notably, evidence indicating that heat-treated platelet-poor plasma may limit growth-factor activity suggests that preparation parameters exert a direct influence on clinical performance [21]. Therefore, future research employing Alb-PRF should prioritize multicenter collaboration under harmonized, standardized preparation protocols to improve reproducibility and validity.

Comparison with other PRF variants

Because different PRF variants vary in fibrin architecture, cellular composition, and growth-factor release kinetics, comparative analyses are essential to accurately position Alb-PRF in clinical practice. A-PRF, Alb-PRF, and i-PRF are third-generation modifications of PRF that aim to enhance mechanical stability and extend growth-factor release through thermal and centrifugation adjustments [25].

As summarized in Table 4, Alb-PRF demonstrates a distinct, prolonged release profile and marked soft-tissue biomodulatory potential, primarily attributed to the albumin gel formed from heat-treated platelet-poor plasma [21, 46]. Nonetheless, current evidence does not support the use of Alb-PRF as a primary agent for hard-tissue regeneration; instead, it should be applied in combination with grafts or barrier membranes for optimal outcomes.

Table 4 Comparative structural and biological characteristics of major PRF variants, including Alb-PRF. Alb-PRF is characterized by a dense fibrin–albumin matrix and a prolonged release profile; however, evidence supporting its superiority over other PRF variants in hard-tissue regeneration remains limited [2, 18, 19, 39, 47]Strengths of the available evidence

The available literature provides several notable strengths. First, the biological rationale of Alb-PRF is relatively well characterized, particularly regarding the formation of a heat-stabilized fibrin–albumin matrix and its potential for sustained growth-factor release [21]. Second, despite the limited number of studies, clinical investigations across different indications have consistently suggested favorable effects on early postoperative healing, pain, and edema control [21, 33, 39]. Third, the inclusion of both clinical and preclinical in vivo evidence contributes to a broader understanding of the biological behavior and translational relevance of Alb-PRF.

Limitations of the present systematic review

Several limitations of the present systematic review should be acknowledged. First, the number of available studies was limited, and most clinical investigations were characterized by small sample sizes, single-center designs, and relatively short follow-up periods, thereby restricting external validity and long-term interpretation. Second, substantial heterogeneity existed across the included studies with respect to surgical indication, study design, comparator groups, Alb-PRF preparation parameters, and reported outcome measures, which precluded quantitative synthesis. Third, some included studies presented methodological concerns, including limited reporting of allocation concealment, non-comparative designs, or potential performance and detection bias. Fourth, evidence regarding hard-tissue regeneration remains especially limited, making it difficult to draw robust conclusions on the regenerative predictability of Alb-PRF beyond early soft-tissue healing. These limitations underline the need for future well-designed, multicenter randomized controlled trials with standardized protocols and longer follow-up periods.

Recommendations for future research 1.

Conduct multicenter randomized controlled trials with follow-up periods of ≥12 months to verify the long-term stability and clinical predictability of Alb-PRF outcomes.

2.

Standardize Alb-PRF preparation parameters—particularly heating duration, albumin-to-serum ratio, and centrifugation settings—to minimize methodological heterogeneity and enhance reproducibility across studies.

3.

Evaluate biological and immunological markers (e.g., TGF-β1, IL-10, VEGF, pSTAT3, IL-17) in parallel with clinical endpoints to clarify the underlying mechanisms of action.

4.

Compare Alb-PRF with other platelet-derived biomaterials (L-PRF, i-PRF, and A-PRF) and its combinations with grafts, membranes, or soft-tissue substitutes to determine its relative regenerative potential in different clinical indications, such as peri-implant phenotype management, papilla stability, and soft-tissue volume preservation after extraction.

Clinical positioning of Alb-PRF based on biological function

Based on the synthesis of current clinical outcomes and biological rationale, Alb-PRF should not be interpreted as a universal regenerative material but rather as a context-dependent adjunct with indication-specific utility. The indication-specific clinical positioning of Alb-PRF is summarized in Table 5. Overall, the currently available evidence suggests that Alb-PRF provides its most consistent benefit during the early healing phase, particularly by supporting soft-tissue stability, epithelial maturation, and postoperative comfort. In contrast, evidence for periodontal and peri-implant hard-tissue regeneration remains limited, heterogeneous, and insufficient for definitive clinical recommendations. Accordingly, Alb-PRF should presently be interpreted primarily as an indication-specific adjunctive biomaterial rather than a stand-alone regenerative substitute.

Table 5 Evidence-based clinical positioning of Alb-PRF according to its biological function in periodontal and peri-implant therapy. This table summarizes indication-specific recommendations regarding the use of Alb-PRF as a stand-alone material or as an adjunctive biomaterial in periodontal and peri-implant therapies