A sequential defense-nourishment strategy enabled by thermosensitive core-shell microneedles for synergistic tendon repair

Achilles tendon rupture is a common sports injury, yet clinical tendon repair remains challenging. Current therapeutic approaches lack the ability to temporally regulate the injury microenvironment, hindering the synergy between anti-inflammatory defense and tissue regeneration. To address this, an innovative "sequential defense nutrition" synergistic strategy based on thermosensitive core-shell microneedles is proposed for efficient repair of complex tendon injuries. The study designed and fabricated core-shell microneedles using thermosensitive hydroxybutyl chitosan (HBC) as the matrix, with a core encapsulating growth factor-rich platelet-rich plasma (PRP) and a shell loaded with a proanthocyanidin-copper metal-phenolic network (PCCu) possessing both antioxidant and antibacterial functions. Leveraging the temperature-responsive gelation of HBC, this intelligent delivery system achieves stable anchoring and sustained release after implantation, overcoming the limitation of conventional delivery systems that are prone to displacement in deep tissue. At the injury site, the PCCu in the shell rapidly releases first, clearing reactive oxygen species (ROS) and inhibiting bacterial proliferation to swiftly establish an anti-inflammatory and anti-infective microenvironment. Subsequently, the PRP core provides programmed sustained release of growth factors, continuously supplying bioactive signals necessary for the proliferation and differentiation of tendon-derived stem cells. <i>In vitro</i> experiments confirmed that the system exhibits excellent antioxidant and broad-spectrum antibacterial activities and effectively promotes tenogenic differentiation. In a rat Achilles tendon injury model, the microneedle patch significantly reduced inflammation, promoted aligned and dense collagen fiber deposition, and consequently enhanced the biomechanical strength of the tendon, achieving in situ functional regeneration of the tendon defect. This work is the first to combine thermosensitive core-shell microneedles with a "defense-nutrition" sequential delivery strategy, which holds promising application prospects in sports medicine and tissue engineering.