Approaches to scarless burn wound healing: application of 3D printed skin substitutes with dual properties of anti-infection and balancing wound hydration levelsResearch in context
Shuying Chen,
Yahui Xiong,
Fan Yang,
Yanke Hu,
Jinghao Feng,
Fei Zhou,
Zhonghua Liu,
Hengdeng Liu,
Xiaogang Liu,
Jingling Zhao,
Zhaoqiang Zhang,
Lei Chen
Affiliations
Shuying Chen
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Yahui Xiong
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Fan Yang
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Yanke Hu
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Jinghao Feng
Guangzhou Panyu Central Hospital, Guangzhou 511400, China
Fei Zhou
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Zhonghua Liu
South China Agricultural University, Guangzhou 510642, China
Hengdeng Liu
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Xiaogang Liu
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Jingling Zhao
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Zhaoqiang Zhang
Department of Oral and Maxillofacial Surgery, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou 510280, China; Corresponding author.
Lei Chen
Department of Burn, Wound Repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Engineering Technology Research Center of Burn and Wound Accurate Diagnosis and Treatment Key Technology and Series of Products, Sun Yat-sen University, Guangzhou 510080, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author. Department of Burn, Wound repair & Reconstruction, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Summary: Background: Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors. Methods: A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c. Findings: DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson’s trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing. Interpretation: This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties. Funding: Shown in Acknowledgements.
