Abstract

Anterior cruciate ligament (ACL) reconstruction remains clinically challenging due to persistent inflammation and poor tendon-bone integration. To address these issues, we engineered a bioactive multiphasic textile scaffold (PGMR) featuring a mechanically supportive polylactic acid (PLA) microfiber core and a spatially functionalized electrospun outer layer. This spatially engineered scaffold incorporates nano‑magnesium oxide (nMgO)-enhanced bone segments at both ends for osteogenesis and a central tendon segment functionalized with PLA-resveratrol (Res) conjugates to enable sustained immunomodulation. The loading of PLA-Res was verified in vitro to exert no significant effect on the mechanical properties of the yarn. The PGMR scaffold significantly modulated macrophage responses by sustaining the release of Res over 42 days in vitro. Compared with the PLA group and the control group, the PGMR scaffold downregulated the expression of tumor necrosis factor-α (TNF-α) while upregulating the expression of interleukin-10 (IL-10) in macrophages. Consequently, it attenuated oxidative stress, promoted M2 macrophage polarization, and contributed to the resolution of inflammation. Furthermore, it upregulated osteogenic markers and facilitated angiogenic tubule formation, and exhibited potent antibacterial activity against S. aureus and E. coli. In a rabbit ACL reconstruction model, at 12 weeks, the PGMR group displayed a 193% increase in the ratio of bone volume to total volume (BV/TV) (26.63 ± 1.27%) compared with the control group (9.08 ± 3.46%, p  < 0.01), accompanied by reduced inflammatory cell infiltration and enhanced collagen maturation. This study presents a spatiotemporally functionalized scaffold that synergistically coordinates immunomodulation and osteogenesis, offering a promising strategy for enhancing functional outcomes in ACL reconstruction.