Fabrication of 3D-Printed Adhesive Microneedle Patch Loaded with Codoped Hydroxyapatite in Deep-Tissue Infective Wound Healing

Deep-tissue wounds are challenging to heal due to improper delivery of therapeutic agents to damaged tissues and muscles. Recent developments in deep-tissue penetrating microneedle patches (MNPs) have made significant progress. However, currently marketed systems lack (a) innovative therapeutics influencing all four stages of wound healing; (b) adhesiveness of the designed patch; and (c) the use of natural biomaterials with inherent bioactive properties. Recent developments in hydroxyapatite (HAP) have significantly expanded its possibilities in tissue regenerative applications due to its inherent biological properties. In this study, three hexagonal hydroxyapatite (HAP) codoped with cerium (Ce) and magnesium (Mg) at varying concentrations (2% = 1Ce-1Mg, 5% = 2.5Ce-2.5Mg, and 10% = 5Ce-5Mg) and 2 control groups doped only with Ce (2.5Ce HAP) and Mg (2.5Mg HAP) were synthesized. Following various <i>in vitro</i> tests, the 2.5Ce-2.5Mg codoped HAP was identified as a lead due to its minimal cytotoxicity and maximum <i>in vitro</i> antibacterial activity. Digital light processing (DLP) 3D printing was utilized to fabricate an adhesive microneedle patch (MNP) incorporated with the 2.5Ce-2.5Mg codoped HAP (MNP+2.5Ce-2.5Mg HAP), which facilitated rapid liver hemostasis and repair of skin wound healing within 12 days in an <i>in vivo</i> infective rat model. MNP+2.5Ce-2.5Mg HAP has strong potential for clinical translation in the rapid repair of chronic wounds.