Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system. How to effectively deliver drugs to the site of spinal cord injury lesions through the blood spinal cord brain barrier (BSCB) has always been a challenge. There is an urgent need for developing a controllable and effective method to continuously release drug for SCI repair. Microneedles are a promising drug delivery method, however, how to control drug release smartly from microneedles remains a cutting-edge field. Herein, a NIR triggered photothermal responsive microneedles patch with Au@polyphenol nanospheres encapsulated was designed for SCI repair. By regulating the NIR irradiation, the thermal swelling rate of the microneedles can be precisely controlled. Therefore, the releasing of Au@polyphenol nanospheres from the microneedles could be controlled. Gold nanoparticles are known as nanozyme in photothermal therapy. Polyphenol nanospheres released from microneedles are helpful in promoting spinal cord injury repair by modulating mitochondrial ROS microenvironment. This NIR responsive microneedles array patch loaded with gold@polyphenol nanospheres has the advantages of effectively clearing reactive oxygen species, promoting mitochondrial autophagy, rebuilding redox balance, and reducing neuronal apoptosis.
Defective diabetic wound healing is a major clinical challenge, where hyperglycemia at the wound site induces excessive reactive oxygen species (ROS) which activate the MAPK pathway (particularly p38 MAPK), resulting in sustained release of inflammatory factors and cellular damage/apoptosis. Polyphenols are efficient ROS scavengers which reduce the level of inflammation at the wound site and promote wound healing, but the low bioavailability limits their biomedical application. This study developed a simple and highly efficient method for preparing proanthocyanidin (PC) capsules through hydrogen bonding and hydrophobic interactions among PC molecules. PC capsules can continuously scavenge free radicals and release proanthocyanidins, significantly enhancing their bioavailability. A single dose of PC capsules accelerates wound healing in diabetic mice by regulating the p38 MAPK signaling cascade, reducing inflammatory mediator concentration, inhibiting cell apoptosis, and remodeling the wound microenvironment. This research makes an important contribution to the field of enhancing polyphenol bioavailability for wound healing and reveals the potential of modulating the MAPK pathway for treating other inflammation and oxidative stress-related diseases.