Theranostics 2021; 11(12):5911-5925. doi:10.7150/thno.56266

Research Paper

Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg2+/curcumin from injectable self-healing hydrogels

Baojun Chen1*, Yongping Liang2*, Jing Zhang3*, Lang Bai1, Meiguang Xu1, Qian Han1, Xuezhe Han1, Jintao Xiu1, Meng Li1, Xiaoling Zhou1, Baolin Guo2✉, Zhanhai Yin1✉

1. Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
2. Frontier Institute of Science and Technology, and State Key Laboratory for Mechanical Behavior of Materials, and Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, 710049, China.
3. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. School of Medicine, Northwest University, 229 Taibai North Road, Xi'an 710069, China.
*These authors contributed equally to this work.

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Citation:
Chen B, Liang Y, Zhang J, Bai L, Xu M, Han Q, Han X, Xiu J, Li M, Zhou X, Guo B, Yin Z. Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg2+/curcumin from injectable self-healing hydrogels. Theranostics 2021; 11(12):5911-5925. doi:10.7150/thno.56266. Available from https://www.thno.org/v11p5911.htm

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Abstract

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.

Keywords: anti-inflammation, pro-chondrogenesis, hydrogels, tendon-to-bone healing, rotator cuff, synergistic effects