CHEN-HSIANG KUANWang, Yi-NingYi-NingWangLiao, En-FengEn-FengLiaoWang, Wei-HungWei-HungWangKung, Pin-JuiPin-JuiKungHuang, Wei-YuanWei-YuanHuangChen, Shih-HengShih-HengChenChen, Shih-HsienShih-HsienChenHu, Jin-JiaJin-JiaHuSUNG-JAN LINWang, Tzu-WeiTzu-WeiWang2025-09-192025-09-192025-08-20https://scholars.lib.ntu.edu.tw/handle/123456789/732199Wound healing is a complex process that, when disrupted, can result in hypertrophic scars or keloids, causing significant physical and psychological discomfort. Despite advances in understanding fibrotic scar formation, achieving scarless healing remains challenging. Inspired by fetal wound healing, this research aims to develop a viscoelastic hydrogel mimicking fetal extracellular matrix properties. The hydrogel comprises hyaluronic acid and alginate, forming reversible dynamic Schiff base and ionic bonds. Interleukin-10 (IL-10), an anti-inflammatory cytokine, is encapsulated using polyelectrolyte complex nanoparticles (PCNs), allowing sustained release and mitigating scar formation by inhibiting inflammatory responses. The results show that this hydrogel demonstrates stress relaxation and self-healing abilities, mimicking the natural characteristics of the extracellular matrix. Additionally, cross-linking with calcium ions induces spontaneous hydrogel contraction, facilitating wound closure and providing tension shielding around the wound site. Such action effectively relieves stress in the wound milieu, reducing the likelihood of fibroblasts differentiation into myofibroblasts and preventing excessive collagen deposition. The viscoelastic hydrogel significantly enhances wound healing by integrating immunomodulatory and tension-shielding properties, thereby creating an optimal environment for scarless healing.enimmunomodulationscarless healingtension shieldingtissue engineeringviscoelastic hydrogel[SDGs]SDG3journal article10.1002/adhm.20250195440833245