Dual dynamic cross-linked self-healing chitosan-based hydrogels for microenvironmental reconstruction maintaining mitochondrial homeostasis to ameliorate tendinopathy progression

  • Int J Biol Macromol. 2025 Dec 19;338(Pt 2):149788. doi: 10.1016/j.ijbiomac.2025.149788.
Shibo Xu  1 ,  Pan Huang  1 ,  Zhiquan Zhu  1 ,  Lihang Zhang  1 ,  Yuanqing Cai  1 ,  Yangping Wang  2 ,  Yihang Yu  1 ,  Hong Tang  1 ,  Molong Chen  1 ,  Chenke Zhang  1 ,  Xuting Bian  1 ,  Yiyi Lin  3 ,  Lin Guo  4
Affiliations
  • 1. State Key Laboratory of Trauma, Burn and Combined Injury, Department of Orthopedics/Sports Medicine Center, First Affiliated Hospital of Army Medical University, Chongqing, 400038, China.
  • 2. State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
  • 3. Department of Otorhinolaryngology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. Electronic address: [email protected].
  • 4. State Key Laboratory of Trauma, Burn and Combined Injury, Department of Orthopedics/Sports Medicine Center, First Affiliated Hospital of Army Medical University, Chongqing, 400038, China. Electronic address: [email protected].
PMID: 41423101 DOI: 10.1016/j.ijbiomac.2025.149788
Abstract

Tendinopathy is a disease of the musculoskeletal system resulting from excessive or abnormal mechanical loading of tendons. Reconstruction of disorganized fibers remains a preceding issue and challenge in sports medicine. Therefore, developing novel delivery systems to promote regeneration after tendinopathy is imminently desired. A dual-dynamic crosslinked framework was constructed here through ligand bonds created between the amino or carboxyl groups in gelatin and Fe3+, as well as hydrogen-binding between gelatin and curcumin-grafted carboxymethyl chitosan (CMCS). Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) analyses indicated that the iron was uniformly distributed in the porosity structure. G-CM@Cur/Fe system combines excellent adhesion, sustained drug release, and anti-inflammatory properties, enabling responsive degradation in the injury area of tendons for the on-demand release of curcumin. Stained slices indicated the 2-week intervention reduced the Bonar score in tendinopathy by approximately 61.7 %. The G-CM@Cur/Fe exhibits reduced inflammation and ordered Collagen fibers alignment. In this study, a multifunctional hydrogel was designed to sustain curcumin release and support mitochondrial homeostasis and immune microenvironment remodeling, providing a potential therapeutic approach for tendinopathy.

Keywords
Curcumin; Dual dynamic cross-linked; Self-healing; Tendinopathy; iron ions.
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