Engineering Regenerative Fibrin Scaffold from Balanced Protein-Concentrate Plasma: Structural and Biochemical Characterization

<b>Background:</b> This study evaluates the impact of fibrinogen enrichment on the structural, mechanical, and bioactive properties of fibrin scaffold derived from balanced protein-concentrate plasma (BPCP), an autologous platelet-rich plasma (PRP) formulation with elevated extraplatelet content. <b>Methods:</b> A novel high-fibrinogen BPCP (HF-BPCP) scaffold was produced by combining BPCP platelet lysate with a concentrated fibrinogen solution at a 1:1 ratio, yielding nearly four-fold physiological fibrinogen levels. Comparative analyses between HF-BPCP and standard BPCP included platelet and fibrinogen quantification, scanning electron microscopy (SEM), rheology, indentation, adhesion testing, coagulation kinetics, retraction assays, biodegradation profiling, and growth factor (GF) release kinetics. <b>Results:</b> HF-BPCP displayed significantly denser fibrin networks with thinner fibers, higher porosity, and markedly faster coagulation times compared to BPCP. Mechanically, HF-BPCP exhibited greater stiffness, higher energy dissipation, and more stable adhesion, while almost eliminating scaffold retraction at 24 h. Despite improved early handling and structural integrity, HF-BPCP degraded more rapidly in vitro under tissue plasminogen activator exposure. GF release analysis showed reduced early peaks of platelet-derived factors (TGF-β1, PDGF-AB, VEGF) but sustained release thereafter, while extraplatelet factors (IGF-1, HGF) exhibited similar profiles between scaffolds. <b>Conclusions:</b> These results indicate that fibrinogen enrichment synergizes with the elevated extraplatelet protein profile of BPCP to enhance scaffold mechanical stability, handling properties, and controlled GF delivery. HF-BPCP combines the adhesive, structural, and bioactive features of fibrin sealants with the regenerative potential of PRP, offering a fully autologous alternative for clinical applications requiring rapid coagulation, high mechanical support, and sustained GF availability. Further preclinical and clinical studies are needed to evaluate therapeutic efficacy in the regenerative medicine field.