DOI: 10.25442/hku.29097113
title: Supporting data for "Development of smart biomaterial-based therapeutic platforms for infected wound healing"

description: Wound infection significantly impedes the normal wound-healing process, leading to detrimental outcomes, including inflammation, scarring, and severe pain. Furthermore, the colonization of diverse pathogenic species at the wound site formed complex biofilms, which are highly resistant to conventional antibiotics, increasing the risk of antimicrobial resistance and invasive systemic infection. Over the years, various antimicrobial platforms have been developed to address this issue by controlling the drug release in a stimuli-responsive manner. However, majority of the reported platforms have primarily focused on pathogen eradication while overlooked the infected tissue healing and protective immunity. This thesis presents the development of a series of stimuli-responsive therapeutic carriers, fabricated through chemical conjugation, and investigates their therapeutic, immunomodulatory, and pain-inhibitory effects on infected wound healing.In the first study, a dual stimuli-responsive antimicrobial platform was developed to combat polymicrobial wound infections. This platform utilized a copper-based coordination complex, synthesized by integrating pH-responsive Schiff base (-C=N-) linkers and light-sensitive azo (N=N) moieties. It was demonstrated that under the acidic conditions of the biofilm microenvironment, the dissolvable microneedles embedded complex dissociated to release Cu²⁺ ions, effectively eradicating the polymicrobial infection through the Fenton reaction-mediated oxidative stress. This process was further enhanced by external light exposure. Additionally, post-infection resolution, the complex exhibited anti-inflammatory properties and promoted angiogenesis through macrophage repolarization, thereby accelerating tissue repair.Although conventional antimicrobial strategies eradicate pathogens from the superficial layers, eliminating deep tissue infection remains a significant challenge. To address this, in the second study, we have introduced an electroconductive microneedle patch designed to facilitate deep tissue penetration of antimicrobial agents using external electrical stimulation. The electroconductive patch incorporated with positively charged antimicrobial agents, enabled rapid localized drug release, effectively treating deep cutaneous infections. Furthermore, we have also demonstrated that the synergistic effect of the drug with the external electric stimulation activates the cutaneous sensory neurons and induces neuro-immune crosstalk mediated by dermal dendritic and -T cells in vivo, for promoting the pathogen removal and improving host protective immunity. Recognizing the importance of sensory neuron-mediated immunomodulation and the inevitable cutaneous pain sensation in the third study, we have developed a novel copper-based porous coordination polymer loaded with a sodium channel blocker for the painless infected wound healing. We have elucidated that under the acidic pH of the infected wound niche, the drug-loaded system eliminates the infection by generating oxidative stress and activating neutrophils through the inhibition of nociceptive neurons mediated calcitonin gene-related peptide signalling. Additionally, this formulation alleviated the spontaneous pain caused during infection by antagonizing the pathogen-secreted neurotoxins through the blocking of calcium channels present on the somatosensory neurons. Collectively, these studies demonstrate the potential of smart antimicrobial platforms to effectively and painlessly treat localized wound infections by leveraging internal and external stimuli such as pH, light, and electricity. The findings suggest that these innovative biomaterial-based therapeutic platforms could be extended to address a wide range of pathological conditions, including diabetes, cancer, and other inflammatory disorders. This dataset contained chapterwise datasets for the thesis submission.