Macrophages play pivotal roles in tissue repair through remarkable functional plasticity, orchestrated by their developmental origins and local microenvironmental cues. Embryonically derived resident macrophages primarily maintain tissue homeostasis, while monocyte-derived macrophages respond predominantly to inflammation and extracellular matrix remodeling. Effective tissue repair requires precise temporal regulation of macrophage polarization, balancing inflammation resolution, angiogenesis, and scar formation. Metabolic reprogramming further enhances macrophage plasticity, enabling adaptation to fluctuating energy demands at injury sites. Emerging evidence also highlights that macrophages integrate biomechanical forces—such as matrix stiffness and shear stress—with biochemical signals to fine-tune their inflammatory and reparative programs. Recognizing this mechanoregulation broadens therapeutic avenues for precisely modulating macrophage behavior in regenerative medicine. Targeting macrophage subsets, polarization states, or metabolic pathways has emerged as a promising therapeutic strategy to optimize healing outcomes. However, the inherent complexity of macrophage heterogeneity presents considerable challenges to therapeutic precision. This review systematically summarizes the multifaceted roles of macrophages in tissue repair, emphasizing how developmental origins dictate functional specificity, dynamic phenotypic transitions, and metabolic adaptability, aiming to advance macrophage-based precision therapeutics for regenerative medicine.

Two new disubstituted maleimides, aspergteroids G–H (1–2), and two trisubstituted butenolides aspergteroids I–J (3–4), along with four known analogs, were isolated and structurally identified from the fermentation extract of soft-coral-associated symbiotic and epiphytic fungus Aspergillus terreus EGF7-0-1. The structures of the new compounds were established mainly via spectroscopic data analyses, and their absolute configurations were determined via X-ray diffraction analysis and comparison of the calculated and experimental electronic circular dichroism. Myocardial protection assays showed that compounds 1, 2, 5, and 6 possess protective effects against tert-butyl hydroperoxide (TBHP)-induced H9c2 (rat myocardial cells) apoptosis at low concentrations. Based on the analyses of the protein–protein interaction (PPI) network and Western blotting, compound 1 may inhibit the apoptosis and inflammatory response of cardiomyocytes after TBHP induction and improve the antioxidant capacity of cardiomyocytes. We speculate that the anti-inflammatory response of compound 1 is suppressed by the glycogen synthase kinase-3 beta (GSK-3β), downregulated by the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and suppressed by the expression of cysteinyl aspartate specific proteinase-3 (caspase-3) and B-cell lymphoma-2 associated X protein (Bax).