Maedeh Alizadeh, Mohammadamin Momeny, Elaheh Khodadoust, Seyed Bagher Mahmoudi, Somayeh Abolghasemi-Dehaghani, Morteza Zarrabi, Masoumeh Nouri, Sanaz Alizadeh
Platelet-rich fibrin (PRF), a natural fibrin matrix enriched with growth factors and cytokines, has gained prominence in regenerative medicine when integrated with biocompatible polymers. This review explores the macromolecular interactions, structural dynamics, and functional efficacy of PRF-loaded polymer composites in wound healing. We analyze how natural (e.g., chitosan, collagen, hyaluronic acid) and synthetic (e.g., PLGA, PCL) polymers modulate the sustained release of PRF-derived bioactive macromolecules, enhancing cellular recruitment, angiogenesis, and extracellular matrix remodeling. Key emphasis is placed on the physicochemical properties (e.g., cross-linking density, degradation kinetics) of these composites and their influence on wound microenvironments. Preclinical and clinical evidence underscores their ability to accelerate chronic and acute wound closure while addressing infections and inflammation. Challenges in standardization, scalability, and long-term stability are critically evaluated. Finally, we highlight emerging trends, including stimuli-responsive polymers and hybrid scaffolds, positioning PRF-polymer systems as a transformative approach in advanced wound care. This work aligns with the journal's focus on macromolecular structure-function relationships in biological applications.