journal article·2026-07

Silk fibroin nanofibers-GelMA hydrogel composite loaded with embryonic fibroblasts: A strategy for enhanced wound healing

Yunyao Bo, Zehui Zhou, Ruitong Dong, Li Sun, Chenxi Li, Lin Zhang, Yuan Yan

Publisher page

Abstract

Synthetic and natural polymer scaffolds have been widely utilized in the design of wound dressings to promote skin tissue regeneration and repair. This study developed an innovative bilayer wound dressing by integrating electrospun silk fibroin (SF) nanofibers into a photo-crosslinkable gelatin methacryloyl (GelMA) hydrogel, creating a GelMA/SF composite scaffold specifically designed as a delivery platform for mouse embryonic fibroblasts (MEFs). The incorporation of SF nanofibers substantially improved the compressive stress, water retention capacity, and structural stability of the hydrogel, thereby providing a more stable and supportive microenvironment for the loaded MEFs. In vitro, the GelMA/SF composite not only supported high cell viability but also significantly enhanced the biological activity of the encapsulated MEFs, facilitating their proliferation and extracellular matrix synthesis. In a full-thickness skin wound model, the MEFs-laden GelMA/SF composite actively accelerated wound healing by effectively modulating inflammation, enhancing re-epithelialization, stimulating angiogenesis, and promoting organized collagen deposition. Moreover, this cell-loaded composite system markedly inhibited pathological scarring and uniquely induced wound-induced hair follicle neogenesis. These findings demonstrate that the GelMA/SF composite serves as a highly effective cell delivery platform, enabling functional skin regeneration with reduced scar formation.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Wound Healing and Treatments · Silk-based biomaterials and applications · Electrospun Nanofibers in Biomedical Applications

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (61)

Show source-provided references
1. Self-adaptive wound dressings for wound healing and repair10.1002/adma.202515854 ↗
2. Cellular and molecular mechanisms of skin wound healing10.1038/s41580-024-00715-1 ↗
3. Wound healing: a cellular perspective10.1152/physrev.00067.2017 ↗
4. The role of cell metabolism in skin wound healing10.34133/research.1000 ↗
5. Wound healing related agents: ongoing research and perspectives10.1016/j.addr.2018.02.007 ↗
6. Extracellular matrix contribution to skin wound re - epithelialization10.1016/j.matbio.2018.01.002 ↗
7. Engineering bioactive scaffolds for skin regeneration10.1002/smll.202101384 ↗
8. Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration10.1186/s12967-021-02752-2 ↗
9. Comparative effectiveness of a bilayered living cellular construct and an acellular fetal bovine collagen dressing in the treatment of venous leg ulcers10.2217/cer-2018-0031 ↗
10. Insight into delivery of dermal fibroblast by non-biodegradable bacterial nanocellulose composite hydrogel on wound healing10.1016/j.ijbiomac.2020.05.011 ↗
11. Theoretical and practical aspects of using fetal fibroblasts for skin regeneration10.1016/j.arr.2017.02.005 ↗
12. Taking cell-matrix adhesions to the third dimension10.1126/science.1064829 ↗
13. Microgels for cell delivery in tissue engineering and regenerative medicine
14. Advances in natural polymer-based hydrogels: synthesis, applications, and future directions in biomedical and environmental fields10.1007/s44347-025-00017-5 ↗
15. Advances of hydrogel combined with stem cells in promoting chronic wound healing10.3389/fchem.2022.1038839 ↗
16. Eumelanin pigment release from photo-crosslinkable methacrylated gelatin-based cryogels: exploring the physicochemical properties and antioxidant efficacy in wound healing10.1016/j.bioadv.2025.214214 ↗
17. Methacrylated gelatin shape-memorable cryogel subcutaneously delivers EPCs and aFGF for improved pressure ulcer repair in diabetic rat model10.1016/j.ijbiomac.2021.12.138 ↗
18. Methacrylated Gelatin as a Scaffold for Mechanically Isolated Stromal Vascular Fraction for Cutaneous Wound Repair10.3390/ijms241813944 ↗
19. Gelatin methacryloyl (GelMA) loaded with concentrated hypoxic pretreated adipose-derived mesenchymal stem cells (ADSCs) conditioned medium promotes wound healing and vascular regeneration in aged skin10.1186/s40824-023-00352-3 ↗
20. Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis
21. 3D bioprinting of prefabricated artificial skin with multicomponent hydrogel for skin and hair follicle regeneration10.7150/thno.104854 ↗
22. Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation10.1016/j.stem.2023.03.005 ↗
23. Bioengineered skin organoids: from development to applications
24. Biofabrication of endothelial cell, dermal fibroblast, and multilayered keratinocyte layers for skin tissue engineering10.1088/1758-5090/aba503 ↗
25. Recent Progress of the Preparation and Application of Electrospun Porous Nanofibers10.3390/polym15040921 ↗
26. Recent progress in cellulose-based electrospun nanofibers as multifunctional materials10.1039/D1NA00508A ↗
27. Silk fibroin and silk-based biomaterial derivatives for ideal wound dressings10.1016/j.ijbiomac.2020.08.041 ↗
28. A novel multifunctional bilayer scaffold based on chitosan nanofiber/alginate-gelatin methacrylate hydrogel for full-thickness wound healing10.1016/j.ijbiomac.2021.10.180 ↗
29. Electrospun silk-BMP-2 scaffolds for bone tissue engineering10.1016/j.biomaterials.2006.01.022 ↗
30. Bioprinting a skin patch with dual-crosslinked gelatin (GelMA) and silk fibroin (SilMA): An approach to accelerating cutaneous wound healing
31. Performance of colombian silk fibroin hydrogels for hyaline cartilage tissue engineering10.3390/jfb13040297 ↗
32. Recent advances in environmentally friendly and green degumming processes of silk for textile and non-textile applications10.3390/polym14040659 ↗
33. Electrospinning and nanofiber technology: fundamentals, innovations, and applications
34. Approaches to scarless burn wound healing: application of 3D printed skin substitutes with dual properties of anti-infection and balancing wound hydration levels10.1016/j.ebiom.2024.105258 ↗
35. Exploring the impact of gelatin bloom strength and degree of functionalization in gelatin methacryloyl bioinks for optimum digital light processing and extrusion 3D bioprinting
36. One-Step Coaxial 3D Printing of Pre-Vascularized Skin Organoid Models with ADSC Microspheres for Enhanced Wound Healing
37. Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms10.1038/nprot.2016.037 ↗
38. Physical dynamic double-network hydrogels as dressings to facilitate tissue repair10.1038/s41596-023-00878-9 ↗
39. Bioengineered skin grafts from patient-derived decellularized extracellular matrix and autologous cells for personalized regenerative
40. Exploring the angiogenic potential of skin patches with endothelial cell patterns fabricated via in-bath 3D bioprinting using light-activated bioink for enhanced wound healing10.1016/j.biomaterials.2025.123575 ↗
41. GelMA loaded with exosomes from human minor salivary gland organoids enhances wound healing by inducing macrophage polarization10.1186/s12951-024-02811-y ↗
42. MiR-17-5p-engineered sEVs encapsulated in GelMA hydrogel facilitated diabetic wound healing by targeting PTEN and p2110.1002/advs.202307761 ↗
43. Youthful brain-derived extracellular vesicle-loaded GelMA hydrogel promotes scarless wound healing in aged skin by modulating senescence and mitochondrial function10.34133/research.0644 ↗
44. Multifunctional fucoidan-loaded Zn-MOF-encapsulated microneedles for MRSA-infected wound healing10.1186/s12951-024-02398-4 ↗
45. Recent trends in gelatin methacryloyl nanocomposite hydrogels for tissue engineering10.1002/jbm.a.37310 ↗
46. Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics
47. Silk fibroin-based biomaterials for tissue engineering applications10.3390/molecules27092757 ↗
48. Conditioned medium-electrospun fiber biomaterials for skin regeneration
49. State-of-the-art review of advanced electrospun nanofiber yarn-based textiles for biomedical applications
50. Electrospinning of botanicals for skin wound healing10.3389/fbioe.2022.1006129 ↗
51. An efficient biosynthetic system for developing functional silk fibroin-based biomaterials10.1002/adma.202570057 ↗
52. Preventing Engrailed-1 activation in fibroblasts yields wound regeneration without scarring10.1126/science.aba2374 ↗
53. Fibroblast heterogeneity in wound healing: hurdles to clinical translation10.1016/j.molmed.2020.07.008 ↗
54. Driving adult tissue repair via re-engagement of a pathway required for fetal healing10.1016/j.ymthe.2022.09.002 ↗
55. Regenerative scar-free skin wound healing10.1089/ten.teb.2018.0350 ↗
56. 3D-bioprinted GelMA/gelatin/amniotic membrane extract (AME) scaffold loaded with keratinocytes, fibroblasts, and endothelial cells for skin tissue engineering10.1038/s41598-024-62926-y ↗
57. Recent advances on 3D-bioprinted gelatin methacrylate hydrogels for tissue engineering in wound healing: a review of current applications and future prospects10.1111/iwj.14533 ↗
58. Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell-based cartilage tissue engineering10.1126/sciadv.aaz5913 ↗
59. Matrix elasticity directs stem cell lineage specification10.1016/j.cell.2006.06.044 ↗
60. Patch repair of deep wounds by mobilized fascia10.1038/s41586-019-1794-y ↗
61. Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering10.3389/fbioe.2023.1271762 ↗