Polylactic acid electrospun membranes coated with chiral hierarchical-structured hydroxyapatite nanoplates promote tendon healing based on a macrophage-homeostatic modulation strategy

Tendon injury is a common and challenging problem in the motor system that lacks an effective treatment, affecting daily activities and lowering the quality of life. Limited tendon regenerative capability and immune microenvironment dyshomeostasis are considered the leading causes hindering tendon repair. The chirality of biomaterials was proved to dictate immune microenvironment and dramatically affect tissue repair. Herein, chiral hierarchical structure hydroxylapatite (CHAP) nanoplates are innovatively synthesized for immunomodulatory purposes and further coated onto polylactic acid electrospinning membranes to achieve long-term release for tendon regeneration adaption. Notably, levorotatory-chiral HAP (L-CHAP) nanoplates rather than dextral-chiral or racemic-chiral exhibit good biocompatibility and bioactivity. In vitro experiments demonstrate that L-CHAP induces macrophage M2 polarization by enhancing macrophage efferocytosis, which alleviates inflammatory damage to tendon stem cells (TDSCs) through downregulated IL-17-NF-<i>κ</i>B signaling. Meanwhile, L-CHAP-mediated macrophage efferocytosis also promotes TDSCs proliferation and tenogenic differentiation. By establishing a rat model of Achilles tendon injury, L-CHAP was demonstrated to comprehensively promoting tendon repair by enhancing macrophage efferocytosis and M2 polarization in vivo, finally leading to improvement of tendon ultrastructural and mechanical properties and motor function. This novel strategy highlights the role of L-CHAP in tendon repair and thus provides a promising therapeutic strategy for tendon injury.