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1.
J Colloid Interface Sci ; 672: 266-278, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38843679

ABSTRACT

Diabetic wound, which is chronic skin disease, poses a significant challenge in clinical practice because of persistent inflammation and impaired angiogenesis. Recently, hydrogen has emerged as a novel therapeutic agent due to its superior antioxidant and anti-inflammatory properties. In this study, we engineered a poly (lactic-co-glycolic acid) (PLGA) electrospun nanofibre membrane loaded with citric acid (CA) and iron (Fe) nanoparticles, referred to as Fe@PLGA + CA. Our in vitro assays demonstrated that the Fe@PLGA + CA membrane continuously generated and released hydrogen molecules via a chemical reaction between Fe and CA in an acidic microenvironment created by CA. We also discovered that hydrogen can ameliorate fibroblast migration disorders by reducing the levels of matrix metalloproteinase 9 (MMP9). Furthermore, we confirmed that hydrogen can scavenge or biochemically neutralise accumulated reactive oxygen species (ROS), inhibit pro-inflammatory responses, and induce anti-inflammatory reactions. This, in turn, promotes vessel formation, wound-healing and accelerates skin regeneration. These findings open new possibilities for using elemental iron in skin dressings and bring us one step closer to implementing hydrogen-releasing biomedical materials in clinical practice.


Subject(s)
Hydrogen , Nanofibers , Polylactic Acid-Polyglycolic Acid Copolymer , Wound Healing , Wound Healing/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Nanofibers/chemistry , Hydrogen/chemistry , Hydrogen/pharmacology , Animals , Iron/chemistry , Metal Nanoparticles/chemistry , Membranes, Artificial , Mice , Humans , Reactive Oxygen Species/metabolism , Particle Size , Surface Properties
2.
Adv Healthc Mater ; 13(17): e2304087, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38531346

ABSTRACT

Volumetric muscle loss (VML) is a severe form of muscle trauma that exceeds the regenerative capacity of skeletal muscle tissue, leading to substantial functional impairment. The abnormal immune response and excessive reactive oxygen species (ROS) accumulation hinder muscle regeneration following VML. Here, an interfacial cross-linked hydrogel-poly(ε-caprolactone) nanofiber composite, that incorporates both biophysical and biochemical cues to modulate the immune and ROS microenvironment for enhanced VML repair, is engineered. The interfacial cross-linking is achieved through a Michael addition between catechol and thiol groups. The resultant composite exhibits enhanced mechanical strength without sacrificing porosity. Moreover, it mitigates oxidative stress and promotes macrophage polarization toward a pro-regenerative phenotype, both in vitro and in a mouse VML model. 4 weeks post-implantation, mice implanted with the composite show improved grip strength and walking performance, along with increased muscle fiber diameter, enhanced angiogenesis, and more nerve innervation compared to control mice. Collectively, these results suggest that the interfacial cross-linked nanofiber-hydrogel composite could serve as a cell-free and drug-free strategy for augmenting muscle regeneration by modulating the oxidative stress and immune microenvironment at the VML site.


Subject(s)
Hydrogels , Muscle, Skeletal , Nanofibers , Regeneration , Animals , Nanofibers/chemistry , Mice , Regeneration/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Polyesters/chemistry , Oxidative Stress/drug effects , Mice, Inbred C57BL , Reactive Oxygen Species/metabolism , Male , RAW 264.7 Cells , Macrophages/metabolism , Tissue Scaffolds/chemistry
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