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

Meimei Fu; Jintao Li; Yiwen Jiang; Yan Shao; Dianxuan Wu; Shaozi Zhong; Zhuoyi Huang; Chao Chen; Jinshan Guo; Denghui Xie; Chun Zeng

doi:10.1016/j.mtbio.2026.102964

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

Mater Today Bio. 2026 Feb 26:37:102964. doi: 10.1016/j.mtbio.2026.102964. eCollection 2026 Apr.

Authors

Meimei Fu^{1

2}, Jintao Li¹, Yiwen Jiang^{3

4}, Yan Shao¹, Dianxuan Wu¹, Shaozi Zhong¹, Zhuoyi Huang², Chao Chen¹, Jinshan Guo^{2

3}, Denghui Xie¹, Chun Zeng¹

Affiliations

¹ Department of Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, PR China.
² Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, 1023 Southern Shatai Rd., Guangzhou, 510515, PR China.
³ Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, 215011, PR China.
⁴ School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, PR China.

Abstract

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. In vitro 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.

Keywords: Microneedles; Platelet-Rich Plasma (PRP); Proanthocyanidin-copper; Sequential defense-nutrition strategy; Tendon repair; Thermosensitive cross-linking.