Artificial Intelligence-Assisted Bioinformatics, Microneedle, and Diabetic Wound Healing: A “New Deal” of an Old Drug

Abstract

Diabetic wounds severely influence life, facing grand challenges in clinical treatments. The demand for better treatment is growing dramatically. Diabetic wound healing is challenging because of inflammation, angiogenesis disruptions, and tissue remodeling. Based on sequencing results of diabetic patients' skins and artificial intelligence (AI)-assisted bioinformatics, we excavate a potential therapeutic agent Trichostatin A (TSA) and a potential target histone deacetylase 4 (HDAC4) for diabetic wound healing. The molecular docking simulation reveals the favorable interaction between TSA and HDAC4. Taking advantage of the microneedle (MN) minimally invasive way to pierce the skin barrier for drug administration, we develop a swelling modified MN-mediated patch loaded with TSA to reduce the probability of injection-caused iatrogenic secondary damage. The MN-mediated TSA patch has been demonstrated to reduce inflammation, promote tissue regeneration, and inhibit HDAC4, which provides superior results in diabetic wound healing. We envisage that our explored specific drug TSA and the related MN-mediated drug delivery system can provide an innovative approach for diabetic wound treatment with simple, effective, and safe features and find a broad spectrum of applications in related biomedical fields.

Microneedles for in situ tissue regeneration

“…After being inserted into the tissue, the MNs swell and then the drugs diffuse into the tissue [ 47 , 55 , 56 , 59 ]. Compared to dissolving MNs, hydrogel MNs have a slower and more controlled drug release rate [ 67 ]. In general, the mechanical strength of hydrogel MNs is directly proportional to the concentration and cross-linking time of the material, and the release rate of the drug tends to be inversely proportional [ 68 ].…”

Microneedles: a novel strategy for wound management

“…There have been some MN studies to reduce the inflammatory response at the wound site by delivering anti-inflammatory drugs, immune signaling molecules, etc ., and to reduce ROS levels using biomaterials such as gallnut and PDA. 109,115–118 And there has been noteworthy research in recent years based on MN technology to deliver cells and exosomes to achieve cell therapy. MSC-derived exosomes are nanoscale extracellular vesicles with complex components such as proteins, lipids, and nucleic acids that enable complex immunotherapies and exhibit superior capabilities in tissue repair and regeneration, with high stability, easy storage, and low immunogenicity.…”

Functional Microneedle Patch for Wound Healing and Biological Diagnosis and Treatment

“…The new artificial intelligence technology has brought many new opportunities in the 21st century, such as combining artificial intelligence (AI) with MN technology, developing a new platform for intelligent diagnosis and treatment, and bringing new opportunities for the application of microneedle arrays. Based on this, Xue et al [84] combined MN with AI to design an MNmediated trigoustatin A (TSA) patch (Figure 6C), which can synergistically control the genes at the center of inflammation, tissue regeneration, and diabetic wound treatment. In vitro and in vitro experiments have proved that TSA can inhibit NLRP 3 inflammasome activation, thereby reducing the risk of its mediated macrophage apoptosis.…”

“…Based on this, Xue et al. [ 84 ] combined MN with AI to design an MN‐mediated trigoustatin A (TSA) patch (Figure 6C), which can synergistically control the genes at the center of inflammation, tissue regeneration, and diabetic wound treatment. In vitro and in vitro experiments have proved that TSA can inhibit NLRP 3 inflammasome activation, thereby reducing the risk of its mediated macrophage apoptosis.…”