DOI: 10.1177/22808000261465725 ISSN: 2280-8000

Decellularized camel intestinal submucosa as a cytokine-modulating platform for platelet lysate delivery in full-thickness wound healing

Aliakbar Yousefi-Ahmadipour, Afsaneh Mirzahosseini-Pourranjbar, Fatemeh Asadi, Morteza Khademolhosseini, Mohammad Kazemi Arababadi, Mohammad Reza Mirzaei, Manira Maarof
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Background

Chronic and extensive skin wounds remain a major clinical challenge requiring advanced regenerative strategies. Decellularized extracellular matrix scaffolds and platelet derivatives support tissue repair by providing essential structural and biological signals. This study evaluated decellularized camel small intestine submucosa (CSIS) alone or combined with platelet lysate (PL) for full-thickness skin wound healing in rats.

Methods

CSIS was prepared via detergent-based decellularization and characterized histologically and via DNA quantification. Following in vitro biocompatibility testing with mesenchymal stem cells (MSCs) using an MTT assay, 1.5 × 1.5 cm full-thickness dorsal wounds in male Wistar rats were randomly assigned to control, CSIS, PL, or CSIS+PL groups. Wound closure was tracked macroscopically on days 7, 14, and 21. Wound tissues were analyzed via histopathology, RT-qPCR for inflammatory genes ( CD68, CD28, IL-1, IL-6, TGF-β ), and ELISA for TNF-α and IL-17.

Results

Decellularization efficiently removed cellular components while preserving ECM architecture and supported good MSC viability. In vivo , all treated groups showed faster wound closure than control, with near-complete healing in the CSIS+PL group by day 21 (residual area: 1.02 ± 1.24 mm 2 vs. 33.55 ± 12.45 mm 2 in control, p < 0.05). Histology demonstrated thicker epidermis, more organized dermis, and reduced inflammatory infiltrate in CSIS and especially CSIS+PL wounds. At day 7, CSIS+PL significantly decreased mRNA levels of CD68 , CD28 , and IL-1 , moderately lowered IL-6 , and increased TGF-β compared with control. TNF-α and IL-17 protein levels in wound tissue were also significantly reduced (TNF-α: 4.7 ± 0.9 pg/mg; IL-17: 3.7 ± 0.5 pg/mg in CSIS+PL vs. control, p < 0.01).

Conclusion

CSIS is a biocompatible scaffold that supports skin regeneration, and its combination with PL enhances wound healing by modulating inflammation and promoting tissue remodeling. This strategy may represent a promising approach for the treatment of complex cutaneous defects.

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