Dual-Stage Crosslinking of Gelatin-Alginate Bioink Supplemented with Wharton's Jelly to Generate 3D Bioprinted Scaffolds for Wound Healing Application.

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Title: Dual-Stage Crosslinking of Gelatin-Alginate Bioink Supplemented with Wharton's Jelly to Generate 3D Bioprinted Scaffolds for Wound Healing Application.
Authors: Phan, Nghia Thi Hieu1,2,3 (AUTHOR), Nguyen, Nho Thuan1,2,3 (AUTHOR), Tran, Ha Le Bao1,2,3 (AUTHOR), Nguyen, My Thi Ngoc1,2,3 (AUTHOR) ntnmy@hcmus.edu.vn
Source: Polymers (20734360). Jun2026, Vol. 18 Issue 11, p1331. 20p.
Subjects: Crosslinking (Polymerization), Wound healing, Biomimetic materials, Extracellular matrix, Bioprinting, Burns & scalds
Abstract: Incorporation of extracellular matrix (ECM) components into bioinks can enhance biological functionality but often compromises print fidelity and structural stability. This study developed a dual-stage calcium chloride (CaCl2) crosslinking strategy to incorporate Wharton's jelly-derived ECM (WJ-ECM) into a gelatin-alginate bioink for bioprinted scaffold fabrication. A baseline formulation (BGA) and a WJ-ECM-supplemented formulation (BGAE, 1 mg/mL) were pre-crosslinked with 14 mM CaCl2 prior to extrusion, followed by secondary crosslinking in 0.5 M CaCl2 post-printing. Both formulations exhibited comparable viscosity (20–180 kcP) and high print fidelity (Pr = 0.99 ± 0.01 for BGA; 0.95 ± 0.01 for BGAE), with scaffolds displaying well-defined architecture and over 84% of pores within the target range (160–270 µm). FTIR analysis confirmed WJ-ECM incorporation without detectable alteration of the primary matrix structure. Both scaffolds were non-cytotoxic and supported fibroblast viability; BGAE constructs showed greater cell coverage over 14 days when surface-seeded and more stable fluorescence intensity through 28 days when encapsulated. In a murine thermal burn model, BGAE-treated wounds demonstrated more advanced re-epithelialization and more continuous epidermal coverage at day 14 compared to controls. These findings indicate that dual-stage crosslinking enables WJ-ECM integration while preserving printability, offering a practical platform for bioactive skin tissue engineering applications. [ABSTRACT FROM AUTHOR]
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Abstract:Incorporation of extracellular matrix (ECM) components into bioinks can enhance biological functionality but often compromises print fidelity and structural stability. This study developed a dual-stage calcium chloride (CaCl2) crosslinking strategy to incorporate Wharton's jelly-derived ECM (WJ-ECM) into a gelatin-alginate bioink for bioprinted scaffold fabrication. A baseline formulation (BGA) and a WJ-ECM-supplemented formulation (BGAE, 1 mg/mL) were pre-crosslinked with 14 mM CaCl2 prior to extrusion, followed by secondary crosslinking in 0.5 M CaCl2 post-printing. Both formulations exhibited comparable viscosity (20–180 kcP) and high print fidelity (Pr = 0.99 ± 0.01 for BGA; 0.95 ± 0.01 for BGAE), with scaffolds displaying well-defined architecture and over 84% of pores within the target range (160–270 µm). FTIR analysis confirmed WJ-ECM incorporation without detectable alteration of the primary matrix structure. Both scaffolds were non-cytotoxic and supported fibroblast viability; BGAE constructs showed greater cell coverage over 14 days when surface-seeded and more stable fluorescence intensity through 28 days when encapsulated. In a murine thermal burn model, BGAE-treated wounds demonstrated more advanced re-epithelialization and more continuous epidermal coverage at day 14 compared to controls. These findings indicate that dual-stage crosslinking enables WJ-ECM integration while preserving printability, offering a practical platform for bioactive skin tissue engineering applications. [ABSTRACT FROM AUTHOR]
ISSN:20734360
DOI:10.3390/polym18111331