Li Liangtao
School of Medicine, Jinan University, Guangzhou, China.
Front Drug Deliv. 2025 Jul 1;5:1598145. doi: 10.3389/fddev.2025.1598145. eCollection 2025.
Gene therapy, a pivotal cornerstone in biomedical research, has emerged as a transformative approach for addressing a wide spectrum of dermatologic conditions, including hereditary disorders, chronic wounds, and immune related skin diseases. The skin, with its expansive surface area and regenerative capacity, serves as an ideal platform for localized gene delivery. However, conventional gene therapy strategies face critical limitations, such as high costs, suboptimal transfection efficiency, immunogenicity, and off-target effects. In this context, gene hydrogels have emerged as an innovative paradigm, offering tailored physicochemical and biological functionalities to overcome these challenges. Gene hydrogels are distinguished by their tunable morphologies (e.g., particulate or bulk gel configurations), which enable precise control over therapeutic release kinetics and spatial distribution. Their three-dimensional polymeric networks recapitulate the extracellular matrix, functioning as bioactive scaffolds that enhance tissue regeneration, facilitate cell migration, and accelerate wound healing. By integrating stimuli-responsive polymers, these hydrogels achieve spatiotemporal control of gene delivery, improving target specificity while minimizing systemic exposure. Furthermore, their inherent biocompatibility and biodegradability mitigate immunogenic risks and prevent long-term residue accumulation, addressing pivotal safety concerns in clinical translation. This review systematically examines the multifaceted advantages of gene hydrogels, including their ability to bypass the stratum corneum barrier, protect genetic payloads from enzymatic degradation, and sustain localized therapeutic effects over extended periods. Recent advancements in "smart" hydrogels, responsive to pathological cues such as pH fluctuations or matrix metalloproteinase overexpression, further underscore their potential in personalized medicine. By synergizing material science with gene-editing technologies, gene hydrogels represent a revolutionary leap toward precision dermatologic therapies. Future challenges, such as scalable manufacturing and dynamic regulatory mechanisms, are critically analyzed alongside opportunities in intelligent material design and interdisciplinary innovation. This comprehensive analysis positions gene hydrogels as a cornerstone for next-generation dermatologic therapeutics, bridging the gap between laboratory innovation and clinical impact.
基因治疗作为生物医学研究的关键基石，已成为一种变革性方法，用于治疗多种皮肤病，包括遗传性疾病、慢性伤口和免疫相关皮肤病。皮肤具有广阔的表面积和再生能力，是局部基因递送的理想平台。然而，传统的基因治疗策略面临着关键限制，如成本高、转染效率欠佳、免疫原性和脱靶效应。在此背景下，基因水凝胶作为一种创新范式应运而生，它具有定制的物理化学和生物学功能，以克服这些挑战。基因水凝胶的特点在于其可调节的形态（如颗粒状或块状凝胶结构），这使得能够精确控制治疗性释放动力学和空间分布。它们的三维聚合物网络模拟细胞外基质，作为生物活性支架发挥作用，增强组织再生、促进细胞迁移并加速伤口愈合。通过整合刺激响应性聚合物，这些水凝胶实现了基因递送的时空控制，提高了靶标特异性，同时将全身暴露降至最低。此外，它们固有的生物相容性和可生物降解性降低了免疫原性风险，并防止长期残留积累，解决了临床转化中的关键安全问题。本综述系统地研究了基因水凝胶的多方面优势，包括其绕过角质层屏障的能力、保护基因载体免受酶降解的能力以及长时间维持局部治疗效果的能力。对诸如pH波动或基质金属蛋白酶过表达等病理线索有响应的“智能”水凝胶的最新进展，进一步凸显了它们在个性化医疗中的潜力。通过将材料科学与基因编辑技术相结合，基因水凝胶代表了向精准皮肤病治疗的革命性飞跃。同时对未来挑战，如可扩展制造和动态监管机制进行了批判性分析，并探讨了智能材料设计和跨学科创新的机遇。这一全面分析将基因水凝胶定位为下一代皮肤病治疗的基石，弥合了实验室创新与临床影响之间的差距。
