# Clinical impact of collagen sponge combined with substance P on maxillofacial trauma repair in rats

**Authors:** Qian Wang, Yong Zhang, Yan Guo, Xiaolan Yang

PMC · DOI: 10.3389/fmed.2025.1631988 · Frontiers in Medicine · 2025-10-16

## TL;DR

Combining collagen sponge with substance P improves maxillofacial trauma healing in rats by reducing inflammation and promoting tissue repair.

## Contribution

The study demonstrates that collagen sponge combined with substance P enhances trauma healing via the TGF-β1/Smad3-VEGF pathway.

## Key findings

- Collagen sponge and substance P combination improved trauma healing rates and collagen fiber content in rats.
- The combination reduced inflammatory markers like IL-6, TNF-α, and MMP-9 while increasing TIMP-1 and TGF-β1/Smad3-VEGF signaling.
- RG 3 showed the best healing outcomes compared to other groups.

## Abstract

Collagen sponge and substance P (SP) can facilitate trauma healing. Therefore, this study aimed to clarify the role and mechanism of collagen sponge combined with SP in maxillofacial trauma healing.

A maxillofacial trauma model was established using rats. The rats were divided into four groups: research group 1 (RG 1; Vaseline gauze and SP), research group 2 (RG 2; Vaseline gauze and collagen sponge), research group 3 (RG 3; collagen sponge and SP), and a control group (CG; Vaseline gauze and normal saline). The trauma healing rate was examined on days 3, 7, and 14 after treatment, and the pathological morphology of the trauma was examined on day 14 after treatment. Hydroxyproline expression; positive expression of basic fibroblast growth factor (bFGF); serum IL-6 and TNF-α levels; matrix metalloprotease-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein levels; and vascular endothelial growth factor (VEGF), TGF-β1, and SMAD3 mRNA levels were detected on day 14 after treatment.

On days 7 and 14 after treatment, the trauma healing rates in all research groups were higher than that in the CG, and the trauma healing rate in RG 3 was higher than that in RG 1 and RG 2. On day 14 after treatment, compared to the CG, the number of inflammatory cells in the rat trauma tissues was reduced in all research groups, while the collagen fiber content was enhanced in all research groups. Compared to RG 1 and RG 2, the number of inflammatory cells in RG 3 was lower, while the collagen fiber content in RG 3 was higher. The tissue hydroxyproline and bFGF levels in all research groups were higher than those in the CG, and the levels in RG 3 were higher than those in RG 1 and RG 2. Compared to the CG, serum levels of IL-6 and TNF-α and tissue levels of MMP-9 were lower across all research groups, while tissue levels of TIMP-1 were elevated in all research groups. The improvements in serum IL-6 and TNF-α levels and tissue MMP-9 and TIMP-1 levels in RG 3 were greater than those in RG 1 and RG 2. Compared to the CG, the mRNA levels of VEGF, TGF-β1, and SMAD3 were higher in all research groups, with RG 3 showing higher levels than RG 1 and RG 2.

Collagen sponge and SP can facilitate the healing of maxillofacial trauma and reduce scar formation after trauma healing. This effect may be related to the TGF-β1/Smad3-VEGF signaling pathway.

## Linked entities

- **Genes:** FGF2 (fibroblast growth factor 2) [NCBI Gene 2247], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318], TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076], VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040], SMAD3 (SMAD family member 3) [NCBI Gene 4088]
- **Proteins:** TGFB1 (transforming growth factor beta 1), SMAD3 (SMAD family member 3)
- **Chemicals:** substance P (PubChem CID 36511), hydroxyproline (PubChem CID 5810), IL-6 (PubChem CID 165368475)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Mmp9 (matrix metallopeptidase 9) [NCBI Gene 81687], Fgf2 (fibroblast growth factor 2) [NCBI Gene 54250] {aka Fgf-2, Fgf2a, bFGF}, Smad3 (SMAD family member 3) [NCBI Gene 25631] {aka Madh3, Smad 3, mad3}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Timp1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 116510] {aka TIMP-1, Timp}, Tff2 (trefoil factor 2) [NCBI Gene 116592]
- **Diseases:** trauma (MESH:D014947), maxillofacial trauma (MESH:D008446), inflammatory (MESH:D007249)
- **Chemicals:** Collagen sponge (-), Hydroxyproline (MESH:D006909)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12571735/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12571735/full.md

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Source: https://tomesphere.com/paper/PMC12571735