BackgroundThe conditioned medium from human dermal fibroblasts (dermal fibroblast‐conditioned medium; DFCM) contains a diverse array of secretory proteins, including growth factors and wound repair‐promoting proteins. Angiogenesis, a crucial process that facilitates the infiltration of inflammatory cells during wound repair, is induced by a hypoxic environment and inflammatory cytokines.MethodsIn this study, we conducted a comprehensive bioinformatic analysis of 337 proteins identified through proteomics analysis of DFCM. We specifically focused on 64 DFCM proteins with potential involvement in angiogenesis. These proteins were further classified based on their characteristics, and we conducted a detailed analysis of their protein–protein interactions.ResultsGene Ontology protein classification categorized these 64 DFCM proteins into various classes, including metabolite interconversion enzymes (N = 11), protein modifying enzymes (N = 10), protein‐binding activity modulators (N = 9), cell adhesion molecules (N = 6), extracellular matrix proteins (N = 6), transfer/carrier proteins (N = 3), calcium‐binding proteins (N = 2), chaperones (N = 2), cytoskeletal proteins (N = 2), RNA metabolism proteins (N = 1), intercellular signal molecules (N = 1), transporters (N = 1), scaffold/adaptor proteins (N = 1), and unclassified proteins (N = 9). Furthermore, our protein–protein interaction network analysis of DFCM proteins revealed two distinct networks: one with medium confidence level interaction scores, consisting of 60 proteins with significant connections, and another at a high confidence level, comprising 52 proteins with significant interactions.ConclusionsOur bioinformatic analysis highlights the presence of a multitude of secretory proteins in DFCM that form significant protein–protein interaction networks crucial for regulating angiogenesis. These findings underscore the critical roles played by DFCM proteins in various stages of angiogenesis during the wound repair process.