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.
Neuronal pyroptosis serves an important role in the progress of neurologic dysfunction following subarachnoid hemorrhage (SAH), which is predominantly caused by a ruptured aneurysm. Hydrogen gas has been previously reported to be an effective anti-inflammatory agent against ischemia-associated diseases by regulating mitochondrial function. The objective of the present study was to investigate the potential neuroprotective effects of hydrogen gas post-conditioning against neuronal pyroptosis after SAH, with specific focus on the mitochondrial ATP-sensitive K
+
(mitoK
ATP
) channels. Following SAH induction by endovascular perforation, rats were treated with inhalation of 2.9% hydrogen gas for 2 h post-perforation. Neurologic deficits, brain water content, reactive oxygen species (ROS) levels, neuronal pyroptosis, phosphorylation of ERK1/2, p38 MAPK and pyroptosis-associated proteins IL-1β and IL-18 were evaluated 24 h after perforation by a modified Garcia method, ratio of wet/dry weight, 2',7'-dichlorofluorescin diacetate, immunofluorescence and western blot assays, respectively. An inhibitor of the mitoK
ATP
channel, 5-hydroxydecanoate sodium (5-HD), was used to assess the potential role of the mitoK
ATP
-ERK1/2-p38 MAPK signal pathway. Hydrogen gas post-conditioning significantly alleviated brain edema and improved neurologic function, reduced ROS production and neuronal pyroptosis, suppressed the expression of IL-1β and IL-18 whilst upregulating ERK1/2 phosphorylation, but downregulated p38 MAPK activation 24 h post-SAH. These aforementioned effects neuroprotective were partially reversed by 5-HD treatment. Therefore, these observations suggest that post-conditioning with hydrogen gas ameliorated SAH-induced neuronal pyroptosis at least in part through the mitoK
ATP
/ERK1/2/p38 MAPK signaling pathway.
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