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]
Copyright of Polymers (20734360) is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: 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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  Data: <searchLink fieldCode="AR" term="%22Phan%2C+Nghia+Thi+Hieu%22">Phan, Nghia Thi Hieu</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nguyen%2C+Nho+Thuan%22">Nguyen, Nho Thuan</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tran%2C+Ha+Le+Bao%22">Tran, Ha Le Bao</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nguyen%2C+My+Thi+Ngoc%22">Nguyen, My Thi Ngoc</searchLink><relatesTo>1,2,3</relatesTo> (AUTHOR)<i> ntnmy@hcmus.edu.vn</i>
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  Data: <searchLink fieldCode="DE" term="%22Crosslinking+%28Polymerization%29%22">Crosslinking (Polymerization)</searchLink><br /><searchLink fieldCode="DE" term="%22Wound+healing%22">Wound healing</searchLink><br /><searchLink fieldCode="DE" term="%22Biomimetic+materials%22">Biomimetic materials</searchLink><br /><searchLink fieldCode="DE" term="%22Extracellular+matrix%22">Extracellular matrix</searchLink><br /><searchLink fieldCode="DE" term="%22Bioprinting%22">Bioprinting</searchLink><br /><searchLink fieldCode="DE" term="%22Burns+%26+scalds%22">Burns & scalds</searchLink>
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  Data: 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]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Polymers (20734360) is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.3390/polym18111331
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      – Code: eng
        Text: English
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        PageCount: 20
        StartPage: 1331
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      – SubjectFull: Crosslinking (Polymerization)
        Type: general
      – SubjectFull: Wound healing
        Type: general
      – SubjectFull: Biomimetic materials
        Type: general
      – SubjectFull: Extracellular matrix
        Type: general
      – SubjectFull: Bioprinting
        Type: general
      – SubjectFull: Burns & scalds
        Type: general
    Titles:
      – TitleFull: Dual-Stage Crosslinking of Gelatin-Alginate Bioink Supplemented with Wharton's Jelly to Generate 3D Bioprinted Scaffolds for Wound Healing Application.
        Type: main
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          Name:
            NameFull: Phan, Nghia Thi Hieu
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            NameFull: Nguyen, Nho Thuan
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            NameFull: Tran, Ha Le Bao
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            NameFull: Nguyen, My Thi Ngoc
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            – D: 01
              M: 06
              Text: Jun2026
              Type: published
              Y: 2026
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