Reprogramming the wound microenvironment: identity remodeling strategies for fibroblasts, keratinocytes, and macrophages

Engineering notes

Key topics: autonomous driving. See the paper for implementation details and experimental results.

Chinese explanation / 中文解读

中文解读待补充：本站会优先为端到端自动驾驶、BEV感知、3D目标检测、轨迹预测、路径规划、LiDAR感知等高价值论文补充中文说明。

Original abstract

The core pathology of chronic non-healing wounds is the dysfunction of wound-repair cells—a molecular defect that conventional passive therapies can hardly correct at its root. Cell reprogramming techniques, by actively rewriting cell identity, have therefore brought a paradigm shift to wound repair. Herein, we propose a systematic “four-dimensional technology toolbox” for wound cell reprogramming, comprising transcription factor-mediated, small-molecule-induced, epigenetic and metabolic regulation, and nanomaterial-assisted delivery. Using this toolbox as the main thread, we comprehensively integrate three core cell-identity reprogramming strategies: fibroblasts (from a profibrotic scar-forming phenotype to a pro-regenerative repair-competent phenotype), keratinocytes (restoring the endogenous regenerative capacity of keratinocytes to reconstruct the epidermal barrier), and macrophages (from a pro-inflammatory pathological state to a reparative homeostatic phenotype). Remedying the principal weaknesses of existing reviews—overemphasis on technique listing, weak mechanistic integration, and lack of translational critique—we dissect the key molecular mechanisms layer by layer and critically evaluate the core clinical-translation bottlenecks, including safety, spatiotemporal precision, and model systems. Finally, we spotlight emerging frontiers such as single-cell multi-omics navigation, AI-driven temporally programmed smart materials, and trained immunity, and discuss how they propel the field from proof-of-concept toward a precision systems-engineering paradigm of “personalized diagnosis → intelligent sequential delivery → closed-loop healing monitoring”. This work not only offers a novel intervention paradigm for the core challenges of treating chronic non-healing wounds like diabetic foot ulcers, but also delivers a panoramic theoretical framework and practical guidance for precision reprogramming therapy—from fundamental mechanisms to clinical translation.

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