Fibroblast Dynamics Following Partial and Deep Burn Injury in a Reconstructed Human Skin Model
10.1007/s13770-025-00770-5
- Author:
Britt van der LEEDEN
;
H. Ibrahim KORKMAZ
;
Sanne ROFFEL
;
Chopie HASSAN
;
Paul P. M. van ZUIJLEN
;
Bouke K. H. L. BOEKEMA
;
Hans W. M. NIESSEN
;
Paul A. J. KRIJNEN
;
Susan GIBBS
- Publication Type:ORIGINAL ARTICLE
- From:
Tissue Engineering and Regenerative Medicine
2026;23(1):185-198
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND:Burn injuries are characterized by extensive and prolonged inflammatory responses that impair wound healing, especially in deep burns. Understanding the post-burn fibroblast dynamics in wound healing is critical to improve recovery and minimize scarring. This study aimed to develop a 3D reconstructed human skin (RhS) burn model to mimic superficial, partial-thickness, and deep burn injuries and assess fibroblast behavior over one week.
METHODS:RhS consisted of a reconstructed epidermis on a fibroblast populated collagen hydrogel dermis. Papillary (fibroblast activation protein; FAP ?) and reticular (FAP-) fibroblasts located themselves in the upper and lower regions respectively within the dermal compartment in line with native skin. Burns of increasing temperatures (70 °C, 110 °C, and 140 °C) were introduced and RhS was analyzed up to one-week post-burn.
RESULTS:Lactate dehydrogenase (LDH) staining for metabolic active cells in tissue sections enabled distinct histological zones to be observed in RhS with partial (110 °C) and deep burns (140 °C): including a viable fibroblast zone (zone V), a mixed dead and viable fibroblast zone (zone M), and a necrotic zone (zone N). Fibroblast migration from the wound edge (M) into the viable area (V) and changes in fibroblast phenotype, particularly an increase in papillary fibroblast markers (FAP ?), were observed, with a marked increased expression of Ki67 in fibroblasts at the burn wound edge (M).Additionally, burn temperature influenced the protein secretion of inflammatory and tissue remodeling mediators SAA, NGAL, MRP8/13, ICAM-1, CCL20, and MMP-9.
CONCLUSION:The RhS burn model enables complex fibroblast dynamics post-burn to be investigated in an organotypic model, providing a platform for studying burn pathophysiology which can be used for evaluating potential therapeutic strategies for enhancing burn wound healing and minimizing scarring in the future.
