Macrophages and other phagocytic cells are central regulators of tendon immunobiology, orchestrating inflammation, tissue repair, and extracellular matrix (ECM) remodeling in the tendons. They derive from circulating monocytes and resident tendon-specific populations, including tenophages. Macrophage polarization along the M1/M2 axis exerts a decisive influence on tendon healing trajectories. Activated M1 macrophages promote the early healing phase for debris clearance initiating the reparative cascade. However, their sustained activity leads to inflammation, ECM degradation, impaired healing, tendinopathy, and heterotopic ossification (HO). Conversely, a timed shift toward activated M2 macrophages promotes resolution of inflammation, angiogenesis, ECM deposition, and fibrocartilage formation, whereas excessive or prolonged M2 activity facilitates adhesion formation, fibrosis, scarring and HO. Recent single-cell and spatial profiling studies showed macrophage heterogeneity across tendon compartments, thereby extending the classical M1/M2 paradigm and underscoring the relevance of macrophages/resident tendon cell’s interaction in tendon-specific local niches. Mechanobiological stimuli (depending on magnitude, frequency and duration) further modulate macrophage phenotypes and tendon healing. Emerging coculture models and human tendon-on-chip systems provide high-resolution platforms for dissecting these spatiotemporal interactions. Promising therapeutic approaches comprise the application of extracellular vesicles, controlled mechanoloading regimens, and immunomodulatory biomaterials demonstrating potential to induce regenerative macrophage signatures for improved healing outcomes. Notably, platelet-rich plasma (PRP) formulations shape macrophage responses: leukocyte-rich PRP preferentially promotes M1 activity whereas leukocyte-poor PRP supports M2 polarization. Thus, mechano- and immunomodulatory strategies can offer precise control over macrophage dynamics. Regarding the Achilles tendon pathologies, such approaches are helpful by directing macrophage-mediated inflammation towards effective tendon healing outcomes.

Anterior cruciate ligament (ACL) rupture causes joint instability and increases the risk of osteoarthritis due to the ligament’s limited healing capacity. Silk, particularly from Bombyx mori, combines high cytocompatibility with robust biomechanical properties. Its main components are fibroin and sericin, with the latter usually being removed to reduce immunogenicity and improve biocompatibility. Silk threads were processed either as raw silk (designated as “untreated”) or subjected to a patented degumming procedure (DE102021118652A1) to obtain purified silk. Both variants were used alone or in combination with poly(L-lactic acid-co-caprolactone) (P(LA-CL)) fibers, yielding four scaffold groups: untreated silk, purified silk, untreated silk/P(LA-CL), and purified silk/P(LA-CL). Three-layer scaffolds were fabricated using a zigzag embroidery pattern. Structural analysis revealed scaffold porosity of ≈38% for silk, ≈46% for purified silk, and up to ≈70% for scaffolds containing P(LA-CL). Uniaxial tensile testing showed that purified silk scaffolds achieved the highest maximum force at break (≈684 N), whereas elongation at maximum force was limited in the hybrid scaffolds—silk/P(LA-CL) ≈ 28% and p-silk/P(LA-CL) ≈ 32%—despite the high intrinsic extensibility of P(LA-CL). All scaffolds supported cell adhesion and showed no cytotoxicity. P-silk and p-silk/P(LA-CL) scaffolds exhibited the highest fibroblast adherence and pronounced paxillin expression, indicating strong cell–material interactions. Gene expression of ligament-related ECM components and connexin 43 was maintained across all groups. These results demonstrate that embroidered silk fibroin scaffolds provide a reproducible architecture with tunable porosity and mechanical properties, supporting fibroblast colonization and ligament-specific ECM expression. Such scaffolds represent promising candidates for ACL tissue engineering and future graft development.