Recombinant collagen microneedles for transdermal delivery of antibacterial copper-DNA nanoparticles to treat skin and soft tissue infections

Skin and soft tissue infections (SSTI) include bacterial infections of the skin, muscles, and connective tissue such as ligaments and tendons. SSTI in patients with immunocompromising diseases may lead to chronic, hard-to-heal infected wounds, resulting in disability, amputation, or even death. To treat SSTI and rebuild the defensive barrier of the skin, here we utilize recombinant type XVII collagen protein (rCol XVII) to construct biodegradable, regenerative collagen microneedles (rCol-MNs) for transdermal delivery of antibacterial agents. Spheroidal copper-DNA antibacterial nanoparticles (Cu-CpG NPs; CpG represents short single-stranded synthetic DNA molecules of cytosine and guanine) are synthesized with copper ions and CpG oligodeoxynucleotides (ODNs), followed by polydopamine (PDA) coating to obtain Cu-CpG@PDA. Doping Cu-CpG@PDA into rCol-MNs yields Cu-CpG@PDA-loaded rCol-MNs. These microneedles combine the photothermal conversion property of PDA, antibacterial properties of copper ions, innate immune activation of CpG ODNs, and skin regenerating ability of rCol XVII, allowing the treatment of SSTI and also regenerating the damaged skin. In a mouse model, we show that the Cu-CpG@PDA-loaded rCol-MNs rescue skin wound infections, facilitate the orderly deposition of collagen at the wound site, and promote the healing of infected full-thickness wounds without noticeable scar formation. rCol-MNs serve as a transdermal delivery vehicle and, simultaneously, a reservoir of skin-regenerating recombinant collagen, bringing combined benefits of infection control and skin regeneration. SIGNIFICANCE STATEMENT: Treatment of soft tissue infection requires the delivery of antibacterial agents into the soft tissue or dermis while providing a regenerating environment for open wounds. Here, we devise recombinant collagen microneedles (rCol-MNs) to meet both requirements.