期刊
THERANOSTICS
卷 11, 期 12, 页码 5911-5925出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.56266
关键词
anti-inflammation; pro-chondrogenesis; hydrogels; tendon-to-bone healing; rotator cuff; synergistic effects
资金
- National Natural Science Foundation of China [82072429, 51973172, 51673155]
- State Key Laboratory for Mechanical Behavior of Materials
- Fundamental Research Funds for the Central Universities
- World-Class Universities (Disciplines) and Characteristic Development Guidance Funds for the Central Universities
- Key Research & Development Program of Shaanxi Province [2020SF-093]
- Natural Science Foundation of Shaanxi Province [2020JC-03, 2019TD-020]
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University [2019LHM-KFKT008]
- Institutional Foundation of the First Affiliated Hospital of Xi'an Jiaotong University [2019ZYTS-02]
A composite hydrogel was developed for promoting rotator cuff tendon-to-bone healing through sustained release of curcumin and Mg2+, demonstrating significant anti-inflammatory and pro-differentiation effects. The hydrogel exhibited excellent biocompatibility and injectability, and enhanced tendon-to-bone healing in a rat model of rotator cuff tear at 8 weeks post-surgery.
Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.
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