Differences between first- and second-generation autologous platelet concentrates.

Autologous platelet concentrates (APCs) applied alone or combined with other biomaterials are popular bioactive factors employed in regenerative medicine. The main biological rationale of using such products is to concentrate blood-derived growth factors and cells into the wound microenvironment to enhance the body's natural healing capacity. First-generation APC is represented by platelet-rich plasma (PRP). While different protocols have been documented for PRP preparation, they overall consist of two cycles of centrifugation and have important limitations related to the use of an anticoagulant first and an activator afterward, which may interfere with the natural healing process and the release of bioactive molecules. The second generation of platelet concentrates is represented by leukocyte and platelet-rich fibrin (L-PRF). L-PRF protocols involve a single centrifugation cycle and do not require the use of anticoagulants and activators, which makes the preparation more straight forward, less expensive, and eliminates potential risks associated with the use of activators. However, since no anticoagulant is employed, blood undergoes rapid clotting within the blood collection tube; hence, a timely management of L-PRF is crucial. This review provides an overview on the most documented protocols for APC preparations and critically discusses the main differences between first- and second-generation APCs in terms of cell content, protein release, and the formation of a 3D fibrin network. It appears evident that the inconsistency in reporting protocol parameters by most studies has contributed to conflicting conclusions regarding the efficacy of different APC formulations and has significantly limited the ability to interpret the results of individual clinical studies. In the future, the use of a standardized classification system, together with a detailed reporting on APC protocol parameters is warranted to make study outcomes comparable. This will also allow to clarify important aspects on the mechanism of action of APCs (like the role of leukocytes and centrifugation parameters) and to optimize the use of APCs in regenerative medicine.