Zhang Li, Chen Yifan, Feng Danna, Xing Zheng, Wang Yuhui, Bai Yang, Shi Dongjian, Li Haihang, Fan Xiaoju, Xia Jiang, Wang Jianhao
School of Pharmacy, Changzhou University, Changzhou 213164, China; Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, Jiangnan University, Wuxi 214122, China.
School of Pharmacy, Changzhou University, Changzhou 213164, China.
J Control Release. 2025 Mar 10;379:191-201. doi: 10.1016/j.jconrel.2025.01.016. Epub 2025 Jan 10.
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.
皮肤和软组织感染（SSTI）包括皮肤、肌肉以及韧带和肌腱等结缔组织的细菌感染。免疫功能低下疾病患者的SSTI可能导致慢性、难以愈合的感染伤口，从而导致残疾、截肢甚至死亡。为了治疗SSTI并重建皮肤的防御屏障，我们利用重组XVII型胶原蛋白（rCol XVII）构建可生物降解的、具有再生功能的胶原蛋白微针（rCol-MNs），用于经皮递送抗菌剂。用铜离子和CpG寡脱氧核苷酸（ODN）合成球形铜-DNA抗菌纳米颗粒（Cu-CpG NPs；CpG代表胞嘧啶和鸟嘌呤的短单链合成DNA分子），然后进行聚多巴胺（PDA）包被以获得Cu-CpG@PDA。将Cu-CpG@PDA掺杂到rCol-MNs中得到负载Cu-CpG@PDA的rCol-MNs。这些微针结合了PDA的光热转换特性、铜离子的抗菌特性、CpG ODN的先天免疫激活作用以及rCol XVII的皮肤再生能力，既能治疗SSTI，又能使受损皮肤再生。在小鼠模型中，我们证明负载Cu-CpG@PDA的rCol-MNs可挽救皮肤伤口感染，促进伤口部位胶原蛋白的有序沉积，并促进感染的全层伤口愈合，且无明显瘢痕形成。rCol-MNs作为一种经皮递送载体，同时也是皮肤再生重组胶原蛋白的储存库，带来了感染控制和皮肤再生的双重益处。意义声明：软组织感染的治疗需要将抗菌剂递送至软组织或真皮层，同时为开放性伤口提供再生环境。在此，我们设计了重组胶原蛋白微针（rCol-MNs）以满足这两个要求。
