Development of a pro‐angiogenic stem cell‐derived vascular cell extracellular matrix‐decorated hyaluronic acid hydrogel
4 affiliations
- 1Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine Royal College of Surgeons in Ireland Dublin Ireland
- 2CÙRAM, Centre for Research in Medical Devices University of Galway Galway Ireland
- 3Department of Medicine, Education and Research Centre Royal College of Surgeons in Ireland Dublin Ireland
- 4Trinity Centre for Biomedical Engineering Trinity College Dublin Dublin Ireland
Abstract
Diabetic foot ulcers (DFU) are debilitating chronic wounds which affect up to a third of diabetic patients. Due to the underlying diabetic pathophysiology, normal wound healing is perturbed. In particular, there is insufficient re‐vascularisation of the wound bed, ultimately leading to the development of chronic wounds. Current treatment protocols are insufficient to stimulate re‐vascularisation and wound closure, ultimately leading to ~20% of patients with a DFU requiring lower limb amputation. Extracellular matrix (ECM)‐derived biomaterials have demonstrated great promise to promote tissue vascularisation and wound repair. In the present study, the overarching goal was to develop a decellularised ECM from human induced pluripotent stem cell (hiPSC)‐derived vascular cells, and incorporate it into a hyaluronic acid‐based hydrogel for wound healing. Vascular differentiation of hiPSCs yielded a heterogenous population containing both CD31 expressing endothelial cells (iEC), and CD31‐negative stromal cells (iSC). ECM deposition by iSCs was stimulated by treatment with ascorbic acid and macromolecular crowder carrageenan. Post‐decellularisation, the ECM composition was analysed by immunofluorescent and histological staining, indicating the presence of ECM components such as fibronectin, fibrillar collagens, perlecan and glycosaminoglycans, all having implications in angiogenic processes. Decellularised ECM accelerated the capacity of iECs to form tube‐like structures when added to cell culture media in 2D. Decoration of hyaluronic acid (HyA)‐based hydrogels with this decellularised ECM enhanced metabolic activity and attachment of both HUVECs and human dermal fibroblasts seeded on these hydrogels. Taken together, this ECM‐decorated HyA‐based hydrogel has the potential to enhance angiogenesis and revascularisation in chronic wound applications such as DFU.
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BibTeX
@article{hosty2026development,
title = {{Development of a pro‐angiogenic stem cell‐derived vascular cell extracellular matrix‐decorated hyaluronic acid hydrogel}},
author = {Louise Hosty and Yu‐Yin Joanne Chang and Martina Konečná and Matthew McGrath and Cormac Murphy and Anja Schweikert and Mari Ozaki and Killian Hurley and Fabio Quondamatteo and Shane Browne},
journal = {Journal of Anatomy},
year = {2026},
month = nov,
doi = {10.1111/joa.70273},
url = {https://doi.org/10.1111/joa.70273},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Development of a pro‐angiogenic stem cell‐derived vascular cell extracellular matrix‐decorated hyaluronic acid hydrogel
AU - Louise Hosty
AU - Yu‐Yin Joanne Chang
AU - Martina Konečná
AU - Matthew McGrath
AU - Cormac Murphy
AU - Anja Schweikert
AU - Mari Ozaki
AU - Killian Hurley
AU - Fabio Quondamatteo
AU - Shane Browne
PY - 2026
DA - 2026/11/04
JO - Journal of Anatomy
DO - 10.1111/joa.70273
UR - https://doi.org/10.1111/joa.70273
AB - Diabetic foot ulcers (DFU) are debilitating chronic wounds which affect up to a third of diabetic patients. Due to the underlying diabetic pathophysiology, normal wound healing is perturbed. In particular, there is insufficient re‐vascularisation of the wound bed, ultimately leading to the development of chronic wounds. Current treatment protocols are insufficient to stimulate re‐vascularisation and wound closure, ultimately leading to ~20% of patients with a DFU requiring lower limb amputation. Extracellular matrix (ECM)‐derived biomaterials have demonstrated great promise to promote tissue vascularisation and wound repair. In the present study, the overarching goal was to develop a decellularised ECM from human induced pluripotent stem cell (hiPSC)‐derived vascular cells, and incorporate it into a hyaluronic acid‐based hydrogel for wound healing. Vascular differentiation of hiPSCs yielded a heterogenous population containing both CD31 expressing endothelial cells (iEC), and CD31‐negative stromal cells (iSC). ECM deposition by iSCs was stimulated by treatment with ascorbic acid and macromolecular crowder carrageenan. Post‐decellularisation, the ECM composition was analysed by immunofluorescent and histological staining, indicating the presence of ECM components such as fibronectin, fibrillar collagens, perlecan and glycosaminoglycans, all having implications in angiogenic processes. Decellularised ECM accelerated the capacity of iECs to form tube‐like structures when added to cell culture media in 2D. Decoration of hyaluronic acid (HyA)‐based hydrogels with this decellularised ECM enhanced metabolic activity and attachment of both HUVECs and human dermal fibroblasts seeded on these hydrogels. Taken together, this ECM‐decorated HyA‐based hydrogel has the potential to enhance angiogenesis and revascularisation in chronic wound applications such as DFU.
SN - 0021-8782
SN - 1469-7580
ER -