3D-printed fish-skin-derived composite dECM hydrogel patch for immunomodulatory and pro-angiogenic diabetic wound repair.
5 affiliations
- 1Department of Biotechnology and Bioinformatics, Korea University, Sejong, Republic of Korea.
- 2Interdisciplinary Major Program in Bio Medical and Data Science Convergence, Korea University, Sejong, Republic of Korea.
- 3Laboratory of Endocrinology and Immune System, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
- 4Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
- 5Digital Healthcare Center, Sejong Institute for Business and Technology (SIBT), Korea University, Sejong, Republic of Korea.
Abstract
Diabetic wounds are sustained by persistent inflammation, oxidative stress, infection susceptibility, and impaired angiogenesis, highlighting the need for bioactive dressings with manufacturable architectures. Here, we developed a methacrylation-free and photopolymerization-free fish-derived composite decellularized extracellular matrix (dECM) hydrogel scaffold by blending tilapia skin-derived dECM (TdECM) with carp skin-derived dECM (CdECM). Rheology-guided screening identified TdECM/CdECM-2, a 1:2 (v/v) blend of TdECM and CdECM, as a printable formulation that combined shear-thinning behavior, thermally induced collagen fibrillogenesis, and extrusion printability. Post-print stabilization with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) preserved lattice architecture and generated highly porous scaffolds with a porosity of 90.3 ± 3.9%. In vitro, the composite scaffold (TdECM/CdECM-2) supported fibroblast, keratinocyte, and endothelial cell growth; promoted keratinocyte migration and endothelial network formation; and reduced Staphylococcus aureus and Pseudomonas aeruginosa survival to 10.5 ± 1.3% and 13.3 ± 3.3%, respectively, in direct-contact assays. Macrophage studies indicated attenuated pro-inflammatory gene expression, increased pro-regenerative macrophage-associated markers, and reduced oxidative stress-associated reactive oxygen species accumulation. In mice with streptozotocin-induced diabetes, TdECM/CdECM-2 increased wound closure to 91.2 ± 3.9% at day 14, compared with 73.2 ± 9.7% in the untreated control and 79.3 ± 12.5% in the porcine skin-derived dECM (PdECM) group, together with improved re-epithelialization, collagen deposition, and cluster of differentiation 31 (CD31)-positive neovascularization, and reduced inflammatory myeloid cell accumulation and macrophage activation. Exploratory single-cell transcriptomic profiling suggested treatment-associated modulation of immune and stromal/endothelial gene programs related to inflammation and angiogenesis. These findings support fish-derived composite dECM scaffolds as printable bioactive wound dressing platforms for diabetic wound repair.
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BibTeX
@article{lee20263dprinted,
title = {{3D-printed fish-skin-derived composite dECM hydrogel patch for immunomodulatory and pro-angiogenic diabetic wound repair.}},
author = {Seong Hyun Lee and Ji Sun Moon and Soyoung Noh and Hyon-Seung Yi and Hyeongjin Lee},
journal = {Materials today. Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103753},
url = {https://europepmc.org/article/MED/42927160},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - 3D-printed fish-skin-derived composite dECM hydrogel patch for immunomodulatory and pro-angiogenic diabetic wound repair.
AU - Seong Hyun Lee
AU - Ji Sun Moon
AU - Soyoung Noh
AU - Hyon-Seung Yi
AU - Hyeongjin Lee
PY - 2026
DA - 2026/10/13
JO - Materials today. Bio
DO - 10.1016/j.mtbio.2026.103753
UR - https://europepmc.org/article/MED/42927160
AB - Diabetic wounds are sustained by persistent inflammation, oxidative stress, infection susceptibility, and impaired angiogenesis, highlighting the need for bioactive dressings with manufacturable architectures. Here, we developed a methacrylation-free and photopolymerization-free fish-derived composite decellularized extracellular matrix (dECM) hydrogel scaffold by blending tilapia skin-derived dECM (TdECM) with carp skin-derived dECM (CdECM). Rheology-guided screening identified TdECM/CdECM-2, a 1:2 (v/v) blend of TdECM and CdECM, as a printable formulation that combined shear-thinning behavior, thermally induced collagen fibrillogenesis, and extrusion printability. Post-print stabilization with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) preserved lattice architecture and generated highly porous scaffolds with a porosity of 90.3 ± 3.9%. In vitro, the composite scaffold (TdECM/CdECM-2) supported fibroblast, keratinocyte, and endothelial cell growth; promoted keratinocyte migration and endothelial network formation; and reduced Staphylococcus aureus and Pseudomonas aeruginosa survival to 10.5 ± 1.3% and 13.3 ± 3.3%, respectively, in direct-contact assays. Macrophage studies indicated attenuated pro-inflammatory gene expression, increased pro-regenerative macrophage-associated markers, and reduced oxidative stress-associated reactive oxygen species accumulation. In mice with streptozotocin-induced diabetes, TdECM/CdECM-2 increased wound closure to 91.2 ± 3.9% at day 14, compared with 73.2 ± 9.7% in the untreated control and 79.3 ± 12.5% in the porcine skin-derived dECM (PdECM) group, together with improved re-epithelialization, collagen deposition, and cluster of differentiation 31 (CD31)-positive neovascularization, and reduced inflammatory myeloid cell accumulation and macrophage activation. Exploratory single-cell transcriptomic profiling suggested treatment-associated modulation of immune and stromal/endothelial gene programs related to inflammation and angiogenesis. These findings support fish-derived composite dECM scaffolds as printable bioactive wound dressing platforms for diabetic wound repair.
SN - 2590-0064
ER -