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<p>Chronic diabetic wounds, due to their complex pathophysiology, present significant clinical challenges. This study describes a novel 3D-printable bigel system designed to co-deliver hydrophilic epigallocatechin gallate (EGCG) and hydrophobic curcumin (Cur), aiming to address the multifactorial causes of impaired diabetic wound healing. The bigel matrix comprises two interpenetrating networks: a β-sitosterol/candelilla-wax oleogel and a chitosan-polyvinyl-alcohol hydrogel. Within these networks, curcumin is housed in the oleogel phase and EGCG in the hydrogel phase. The bigel’s unique bicontinuous structure imparts excellent mechanical properties and enhanced 3D printing characteristics compared to traditional single-phase gels. The excellent 3D printing performance can enable it to be applied to wounds such as ulcers where drug administration is difficult (not pressable or smearable). Moreover, the bicontinuous structure facilitates simultaneous release of both bioactive drugs and significantly improves cutaneous permeation, enabling deep penetration of drugs into wound tissues. Both in vitro and in vivo evaluations demonstrated that bigel-treated wounds healed faster and with superior quality compared to those treated with oleogel or hydrogel alone. RNA sequencing analysis identified key genes and signaling pathways (e.g., Wnt and MAPK) potentially involved in bigel‑mediated immune regulation. Subsequent Western blotting confirmed upregulated p‑ERK and β‑catenin protein expression, indicative of MAPK and Wnt pathway activation, thereby offering preliminary mechanistic insights. Collectively, this study establishes the 3D-printed bigel system as a promising therapeutic platform for chronic diabetic wounds, providing a new strategy to improve clinical outcomes.</p>

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In situ 3D-printable bigel with co-delivered hydrophilic/hydrophobic natural bioactives for enhanced diabetic wound healing

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月28日

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  • Hongyang Guo,
  • Xintong Zhao,
  • Jie Tang,
  • Caihuan Huang,
  • Jie Zheng,
  • Fu Liu,
  • Shiyi Ou,
  • Xiangcai Zou,
  • Zhenzhen Liu,
  • Juanying Ou

摘要

Chronic diabetic wounds, due to their complex pathophysiology, present significant clinical challenges. This study describes a novel 3D-printable bigel system designed to co-deliver hydrophilic epigallocatechin gallate (EGCG) and hydrophobic curcumin (Cur), aiming to address the multifactorial causes of impaired diabetic wound healing. The bigel matrix comprises two interpenetrating networks: a β-sitosterol/candelilla-wax oleogel and a chitosan-polyvinyl-alcohol hydrogel. Within these networks, curcumin is housed in the oleogel phase and EGCG in the hydrogel phase. The bigel’s unique bicontinuous structure imparts excellent mechanical properties and enhanced 3D printing characteristics compared to traditional single-phase gels. The excellent 3D printing performance can enable it to be applied to wounds such as ulcers where drug administration is difficult (not pressable or smearable). Moreover, the bicontinuous structure facilitates simultaneous release of both bioactive drugs and significantly improves cutaneous permeation, enabling deep penetration of drugs into wound tissues. Both in vitro and in vivo evaluations demonstrated that bigel-treated wounds healed faster and with superior quality compared to those treated with oleogel or hydrogel alone. RNA sequencing analysis identified key genes and signaling pathways (e.g., Wnt and MAPK) potentially involved in bigel‑mediated immune regulation. Subsequent Western blotting confirmed upregulated p‑ERK and β‑catenin protein expression, indicative of MAPK and Wnt pathway activation, thereby offering preliminary mechanistic insights. Collectively, this study establishes the 3D-printed bigel system as a promising therapeutic platform for chronic diabetic wounds, providing a new strategy to improve clinical outcomes.