Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries.The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery.Additiona...Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries.The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery.Additionally,insufficient autophagic activity in fibroblasts hinders their apoptosis,leading to excessive matrix deposition.Here,we developed an active microneedle(MN)system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment.Specifically,sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO_(2)bubbles,thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue.The system concurrently encapsulated curcumin(Cur),an autophagy activator,and triamcinolone acetonide(TA),synergistically inducing fibroblast apoptosis by upregulating autophagic activity.In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue.The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index,suppressed collagen I and transforming growth factor-β1(TGF-β1)expression,and elevated LC3 protein levels.These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.展开更多
基金supported by the National Natural Science Foundation of China(No.8217374782373803)+1 种基金the Keynote Project of National Natural Science Foundation of China(No.82330112)the Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province(No.2021TQ060944,China).
文摘Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries.The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery.Additionally,insufficient autophagic activity in fibroblasts hinders their apoptosis,leading to excessive matrix deposition.Here,we developed an active microneedle(MN)system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment.Specifically,sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO_(2)bubbles,thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue.The system concurrently encapsulated curcumin(Cur),an autophagy activator,and triamcinolone acetonide(TA),synergistically inducing fibroblast apoptosis by upregulating autophagic activity.In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue.The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index,suppressed collagen I and transforming growth factor-β1(TGF-β1)expression,and elevated LC3 protein levels.These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.
