Sustained release of magnesium ions mediated by injectable self-healing adhesive hydrogel promotes fibrocartilaginous interface regeneration in the rabbit rotator cuff tear model

Chen, Baojun; Liang, Yongping; Bai, Lang; Xu, Meiguang; Zhang, Jing; Guo, Baolin; Yin, Zhiwei

doi:10.1016/j.cej.2020.125335

Cited by 49 publications

(35 citation statements)

References 78 publications

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“…Injectable hydrogels, due to their physical properties similar to extracellular matrix, may serve as a suitable platform to support osteoblast survival, proliferation, and differentiation, and promote articular-cartilage tissue regeneration. In addition, self-healing hydrogel has been widely used quite successfully combined with diversified fields, such as magnesium ions mediated fibrocartilaginous interface regeneration ( Chen et al, 2020 ), photothermal therapy of infected full-thickness skin wounds ( He et al, 2020 ), and hepatocellular carcinoma therapy by using pH-responsive drug delivery system ( Qu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

Yang

Jing

Wang

et al. 2021

Front. Bioeng. Biotechnol.

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The normal anatomical structure of articular cartilage determines its limited ability to regenerate and repair. Once damaged, it is difficult to repair it by itself. How to realize the regeneration and repair of articular cartilage has always been a big problem for clinicians and researchers. Here, we conducted a comprehensive analysis of the physical properties and cytocompatibility of hydrogels, and evaluated their feasibility as cell carriers for Adipose-derived mesenchymal stem cell (ADSC) transplantation. Concentration-matched hydrogels were co-cultured with ADSCs to confirm ADSC growth in the hydrogel and provide data supporting in vivo experiments, which comprised the hydrogel/ADSCs, pure-hydrogel, defect-placement, and positive-control groups. Rat models of articular cartilage defect in the knee joint region was generated, and each treatment was administered on the knee joint cartilage area for each group; in the positive-control group, the joint cavity was surgically opened, without inducing a cartilage defect. The reparative effect of injectable glycol chitosan/dibenzaldehyde-terminated polyethylene glycol (GCS/DF-PEG) hydrogel on injured articular cartilage was evaluated by measuring gross scores and histological score of knee joint articular-cartilage injury in rats after 8 weeks. The 1.5% GCS/2% DF-PEG hydrogels degraded quickly in vitro. Then, We perform in vivo and in vitro experiments to evaluate the feasibility of this material for cartilage repair in vivo and in vitro.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

Yang

Jing

Wang

et al. 2021

Front. Bioeng. Biotechnol.

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“…Magnesium ion (Mg 2+ ) has been reported to effectively enhance stem cell aggregation and promote fibrocartilage regeneration 20 , 21 . Moreover, our prior work demonstrated that Mg 2+ effectively improved regeneration of the fibrocartilage layer at the tendon-to-bone interface in a rabbit rotator cuff tear model 22 .…”

Section: Introductionmentioning

confidence: 88%

“…Based on our prior work 22 , male Sprague Dawley rats (230-250 g) were used to construct a rotator cuff tear and repair model with the hydrogels injected into the tendon-to-bone interface. Briefly, rats were anesthetized, their skin was prepared, and a longitudinal incision was made over the shoulder joint.…”

Section: Methodsmentioning

confidence: 99%

“…The adhesion and chemotaxis effects of the hydrogels on rat BMSCs were investigated following previously reported procedures with some modifications 20 , 22 , 37 . The details are available in the supplementary information .…”

Section: Methodsmentioning

confidence: 99%

“…Curcumin was loaded in the PF127-CHO micelles, which greatly enhanced its solubility. In this study, we also loaded Mg 2+ into QCS/PF through complexation between Mg 2+ and -NH 2 /NH, -OH in the QCS main chain following our previous study 22 . The Cur&Mg-QCS/PF hydrogel provided a protective environment for stem cells during rotator cuff healing through the anti-inflammatory and antioxidative effects of the released curcumin (Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

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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

Chen¹,

Liang²,

Zhang³

et al. 2021

Theranostics

Self Cite

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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 Mg 2+ 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 Mg 2+ 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 Mg 2+ 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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Magnesium Gradient‐Based Hierarchical Scaffold for Dual‐Lineage Regeneration of Osteochondral Defect

Gao

Dai

Wang

et al. 2023

Adv Funct Materials

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Osteochondral regeneration remains a great challenge due to the limited self‐healing ability and the complexity of its hierarchical structure and composition. Mg2+ and hypoxia are two effective modulators in boosting chondrogenesis. To this end, a double‐layered scaffold (D) consisting of a hydrogel layer on a porous cryogel is fabricated to mimic the hierarchical structure of osteochondral tissue. An Mg2+ gradient is incorporated into the double‐layered scaffold with hypoxia‐mimicking deferoxamine (DFO) embedded in the hydrogel (D‐Mg‐DFO), which remarkably augments the dual‐lineage regeneration of both cartilage and subchondral bone. The higher Mg2+ supplementation from the upper hydrogel, associated with its hypoxia‐mimicking situation and small pore size, exhibits promotive effects on chondrogenic differentiation. The lower Mg2+ supplementation from the bottom cryogel, associated with its interconnected macroporous structure, achieves multiple contributions in stem cell migration from bone marrow cavity, matrix mineralization, and osteogenesis. Furthermore, rabbits’ trochlea osteochondral defects are established to evaluate the regenerative outcome. Compared to control scaffolds containing only Mg2+ or DFO, the D‐Mg‐DFO scaffold presents the best regenerative effect under the synergistic contribution of multiple factors. Overall, this work provides a new design of scaffold toward an effective repair of cartilage defect.

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Sustained release of magnesium ions mediated by injectable self-healing adhesive hydrogel promotes fibrocartilaginous interface regeneration in the rabbit rotator cuff tear model

Cited by 49 publications

References 78 publications

In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

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

Magnesium Gradient‐Based Hierarchical Scaffold for Dual‐Lineage Regeneration of Osteochondral Defect

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Sustained release of magnesium ions mediated by injectable self-healing adhesive hydrogel promotes fibrocartilaginous interface regeneration in the rabbit rotator cuff tear model

Cited by 49 publications

References 78 publications

In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

In vitro and in vivo Study on an Injectable Glycol Chitosan/Dibenzaldehyde-Terminated Polyethylene Glycol Hydrogel in Repairing Articular Cartilage Defects

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

Magnesium Gradient‐Based Hierarchical Scaffold for Dual‐Lineage Regeneration of Osteochondral Defect

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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