Angiogenesis underpins regenerative success and refined autologous platelet concentrates (APCs) are therefore under continual optimization. This study compared optimized thermally-induced albumin hydrogel cross-linked with horizontally centrifuged platelet-rich fibrin (Alb-PRF) against traditional platelet-rich plasma (PRP) and standardized horizontal PRF (H-PRF). Alb-PRF was generated using specific centrifugation protocols. Each APC was co-cultured with human umbilical vein endothelial cells (HUVECs) respectively. Live/dead assay confirmed universal biocompatibility and safety, showing no significant differences in apoptosis among all groups. Additoinally, viability assay revealed possibly superior proliferation by Alb-PRF compared to PRP and H-PRF. Immunofluorescent cytoskeleton and morphology staining showed enhanced proliferative effects with Alb-PRF. Moreover, Alb-PRF significantly increased cell migration. Notably, LPS-induced inflammatory damage led to more apoptotic HUVECs in PRP and H-PRF groups, whereas Alb-PRF rescued this damage. Alb-PRF conferred cytoprotection and upregulated expression of CD31, suggesting an augmented vascular regeneration capacity. Altogether, Alb-PRF outperformed PRP and H-PRF in driving angiogenic potential under both normal and inflammatory conditions. Our findings underscore the translational promise of Alb-PRF, particularly as an innovative solution for wound healing in regenerative medicine. Han, C., Barakat, M. & DiPietro, L. A. Angiogenesis in wound repair: too much of a good thing?Cold Spring Harb Perspect. Biol (2022). https://doi.org/10.1101/cshperspect.a041225 Chong, D. C., Yu, Z., Brighton, H. E., Bear, J. E. & Bautch, V. L. Tortu... [8697 chars]