Mapping the Prosthetic–Host Interactome: From Systemic Inflammation to Biological Integration in Mesh-Enhanced Therapies METs—A Scoping Review

Despite reducing hernia recurrence, synthetic meshes often trigger persistent foreign body responses (FBRs). Mesh-enriched therapies (METs), incorporating autologous cellular components (MSCs, PRP, SVF), can regeneratively reprogram the host-prosthetic interactome. Following PRISMA-ScR guidelines, this scoping review involved a systematic search of PubMed, Embase, and Scopus (2000–2025). We utilized the PCC (Population, Concept, Context) framework to map evidence across systemic inflammation, local FBR, and bio-augmentation strategies. A total of sixty-five studies were synthesized and categorized into three primary thematic pillars. Regarding the Systemic Response (n = 25), the data established a predictable “foreign body signature” characterized by prominent C-reactive protein (CRP) and interleukin-6 (IL-6) spikes within the first 48 h post-implantation. For the Local Foreign Body Reaction (FBR, n = 19), human explant data extending up to 180 months revealed a perpetual, immune-mediated state driven by matrix metalloproteinase-2 (MMP-2) matrix remodeling and the development of “bridging fibrosis.” Finally, concerning Mesh-Enriched Therapy (MET) Integration (n = 21), biological enrichment successfully shifted the M1/M2 macrophage ratio toward a pro-regenerative, CD163+/CD206+ phenotype. While MET consistently enhanced vascular endothelial growth factor (VEGF)-driven angiogenesis and optimized the Collagen I/III ratio, a notable 22.2% discrepancy rate across the literature underscores the critical need for precise transforming growth factor-beta 1 (TGF-β1) dosing and release kinetics to prevent hyper-fibrosis. MET shifts hernia repair from passive mechanical reinforcement to active “biocamouflage” and integration. By modulating the Th1/Th2 rheostat, enriched therapies mitigate chronic inflammation and long-term complications. Standardized clinical trials are essential to optimize the therapeutic window for hybrid integration.