Photothermal Microneedle Hydrogel Patch for Refractory Soft Tissue Injuries through Thermosensitized Anti‐Inflammaging Modulation

Abstract

Soft tissue injuries (STIs) are the most common cause of extremity pain and motion dysfunction. Persistent inflammatory activation of immune cells characterized by senescence‐associated secretory phenotype (SASP) and mitochondrial stress are considered the primary causes of STIs, a pathological process also termed inflammaging. Meanwhile, scavenging excessive “cellular waste” in the inflammaging microenvironment and further activating tissue repair processes remain elusive. Herein, an anti‐inflammaging photothermal hydrogel microneedle patch for treating STIs is developed. Taurine‐loaded Prussian blue nanoparticles (Taurine@PB) are encapsulated in a methacrylate‐based hyaluronic acid hydrogel (HAMA) and further fabricated into taurine@PB@HAMA@microneedles (TPH@MN) patches. The acidic microenvironment of chronic inflammation and mild photothermal effects promote taurine release and anti‐inflammaging immunomodulation, inhibiting mitochondrial stress via the SIRT3‐NF‐κB axis to promote glycolytic metabolic microenvironment of neutrophils reprogramming toward oxidative phosphorylation metabolism. Furthermore, TPH@MN activates macrophage efferocytosis and initiates the process of tissue repair. In mouse models of chronic diabetic wounds and tibialis anterior (TA) muscle injury, TPH@MN inhibits SASP expression and promotes STIs healing through thermosensitized anti‐inflammaging immunomodulation. In summary, TPH@MN circumvents the side effects of systemic administration, providing new translatable options in the treatment modalities for patients suffering from STIs worldwide.

Swellable Microneedles in Drug Delivery and Diagnostics

“…This patch contains taurine-loaded Prussian blue nanoparticles encapsulated in a methacrylate-based hyaluronic acid hydrogel. Its photothermal properties promote healing through thermo-sensitized anti-inflammatory mechanisms, offering an innovative method for treating soft tissue injuries with effective healing and minimized systemic side effects [ 54 ].…”

“…Regulatory and Clinical Validation: Before clinical adoption, MNs must clear stringent regulatory and validation hurdles. It is crucial to conduct in vivo and ex vivo validation studies to demonstrate their practical efficacy and reliability [ 19 , 26 , 50 , 54 , 59 , 75 ]. Comparative studies evaluating swellable MNs against other delivery systems are also beneficial to benchmark their clinical performance and utility [ 71 , 72 ].…”

Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition

“…Prussian blue (PB) is an FDA-approved antidote for thallium or cesium poisoning and can be used as a therapeutic drug to treat radioactive exposure . Hollow mesoporous Prussian blue (HMPB) nanoparticles (NPs) have attracted considerable interest as an excellent controlled drug delivery system due to their distinct advantages, such as hollow mesoporous structure, mesostructured with large surface areas, customizable surface functionalization, and responsiveness to external abnormal acidic environmental stimuli. − For example, Cai et al developed a Mn-containing HMPB that shows pH-responsive release of both Mn 2+ ions and payloads concurrently for theranostic applications . However, these particles possess a large size (>250 nm), and the combination of bimetallic components could compromise the stability of the HMPB crystal structure and cause premature cargo leakage before reaching the lesion site, raising security concerns as Mn elements have been shown to be selectively toxic to pancreatic tissue .…”