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<p>Poor surgical wound healing after major surgery could cause serious consequences. Compared to the interventions after complications occur, preoperative assessment and management of tissue healing capacity could optimize outcomes and alleviate patient distress. Notably, oral mucosa heals faster with reduced scarring after injury compared to skin, making it a natural model of superior healing potential. The cellular and molecular networks underlying these divergent healing capacities were valuable to guide the preoperative assessment and management of tissue healing potential. However, these mechanisms have not been fully elucidated due to a lack of comparative studies on healthy homeostatic tissues and the limitation of bulk-RNA sequencing and in vitro experiments in unveiling complex in vivo microenvironments. Herein, single-cell sequencing datasets from healthy oral mucosa and skin were integrated and subjected to comparative analysis as well as in vivo validation to construct a comparative transcriptional atlas. Our results revealed that oral fibroblasts demonstrate higher activation of transcription factors (FOSB, EGR1, FOS, JUNB, JUN, and CEBPB) and transmit distinctive ligand-receptor interactions involving extracellular matrix components and secretory signals that target vascular endothelial cells (ANGPTL, ncWNT, IGF, PTN, MK, LAMININ, COLLAGEN), basal keratinocytes (IGF, MPZ, TENASCIN, MK, COLLAGEN), and immune cells (CXCL, CCL, TGFB). These features are associated with stronger extracellular matrix synthesis capacity and greater capacities of oral fibroblasts in promoting angiogenesis, epithelial regeneration, and creating a pro-healing immune microenvironment. These insights inform a conceptual framework for preoperative assessment and management of tissue’s inherent healing potential to reduce severe complications after major surgeries, potentially shifting the surgical wound management paradigm from post-complication intervention to proactive management.</p>

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A Comparative Single-Cell Atlas Reveals Pre-injury Signatures of Superior Healing in Oral Mucosa and Informing a New Paradigm for Wound Management

  • 期刊论文

  • 发表日期：

    2026年3月28日

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  • Di Li,
  • CaiHong Fang,
  • Yongyi Wang,
  • Yuanlong Guo

摘要

Poor surgical wound healing after major surgery could cause serious consequences. Compared to the interventions after complications occur, preoperative assessment and management of tissue healing capacity could optimize outcomes and alleviate patient distress. Notably, oral mucosa heals faster with reduced scarring after injury compared to skin, making it a natural model of superior healing potential. The cellular and molecular networks underlying these divergent healing capacities were valuable to guide the preoperative assessment and management of tissue healing potential. However, these mechanisms have not been fully elucidated due to a lack of comparative studies on healthy homeostatic tissues and the limitation of bulk-RNA sequencing and in vitro experiments in unveiling complex in vivo microenvironments. Herein, single-cell sequencing datasets from healthy oral mucosa and skin were integrated and subjected to comparative analysis as well as in vivo validation to construct a comparative transcriptional atlas. Our results revealed that oral fibroblasts demonstrate higher activation of transcription factors (FOSB, EGR1, FOS, JUNB, JUN, and CEBPB) and transmit distinctive ligand-receptor interactions involving extracellular matrix components and secretory signals that target vascular endothelial cells (ANGPTL, ncWNT, IGF, PTN, MK, LAMININ, COLLAGEN), basal keratinocytes (IGF, MPZ, TENASCIN, MK, COLLAGEN), and immune cells (CXCL, CCL, TGFB). These features are associated with stronger extracellular matrix synthesis capacity and greater capacities of oral fibroblasts in promoting angiogenesis, epithelial regeneration, and creating a pro-healing immune microenvironment. These insights inform a conceptual framework for preoperative assessment and management of tissue’s inherent healing potential to reduce severe complications after major surgeries, potentially shifting the surgical wound management paradigm from post-complication intervention to proactive management.