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Role of plasma-derived fibrin on keratinocyte and fibroblast wound healing

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Abstract

Fibrin has excellent biocompatibility and biological properties to support tissue regeneration and promote wound healing. However, the role of diluted fibrin in wound healing has yet to be elucidated as it is commonly used in high concentration. This study was aimed to examine the effects of diluted plasma-derived fibrin (PDF) on keratinocyte and fibroblast wound healing in term of cell proliferation, migration, extracellular matrix (ECM) production and soluble factor secretion. Two PDF concentrations, 10 and 20% (v/v) were tested on keratinocytes and fibroblasts indirectly co-cultured in the transwell system. The control group was cultured with 5% FBS. Results showed that PDF reduced the keratinocyte growth rate and fibroblast migration, and increased the fibroblast ECM gene expression whereby significant differences were found between the 20% PDF group and the 5% FBS group. Similar trend was seen for the 10% PDF group but the differences were not significant. Comparison of the soluble factors between the PDF groups demonstrated that the level of growth-related oncogene alpha, interleukin-8 and epithelial neutrophil-activating peptide-78 were significantly higher in the 10% PDF group, whilst interleukin-1 alpha and granulocyte–macrophage colony stimulating factor were significantly more concentrated in the 20% PDF group. Our results suggested that PDF selectively elevated the expression of collagen type 1 and collagen type 3 in fibroblasts but slowed down the migration in concentration-dependent manner. These novel findings provide new insight into the role of PDF in wound healing and may have important implications for the use of fibrin in skin tissue engineering.

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Abbreviations

PDF:

Plasma-derived fibrin

TESS:

Tissue-engineered skin substitute

col 1:

Collagen type 1

col 3:

Collagen type 3

FN:

Fibronectin

CLSM:

Confocal laser scanning microscope

angio:

Angiogenesis

RE:

Re-epithelialization

TR:

Tissue remodeling

GTF:

Granulation tissue formation

pro-inflam:

Pro-inflammation

NC:

Neutrophil chemotaxis

MC:

Monocyte/macrophage chemotaxis

IL-1α:

Interleukine-1 alpha

TNF-α:

Tumor necrosis factor-alpha

IL-6:

Interleukine-6

G-CSF:

Granulocyte-colony stimulating factor

GM-CSF:

Granulocyte–macrophage colony stimulating factor

TGF-β:

Transforming growth factor-beta

GRO-α:

Growth-related oncogene-alpha

RANTES:

Regulated upon activation, normal T-cell expressed, and presumably secreted

MCP-1:

Monocyte chemoattractant protein-1

IL-8:

Interleukine-8

ENA-78:

Epithelial-derived neutrophil-activating protein 78

SDF-1:

Stromal cell-derived factor-1

HGF:

Hepatocyte growth factor

VEGF-A:

Vascular endothelial growth factor-A

FGF-β:

Fibroblast growth factor-β

PDGF:

Platelet-derived growth factor

EGF:

Epidermal growth factor

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Acknowledgement

This work was supported by Research University Grant (Grant Numbers: DIP-2012-08 and DPP-2013-084) from the Ministry of Higher Education of Malaysia.

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Authors and Affiliations

  1. Tissue Engineering Centre, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000, Kuala Lumpur, Malaysia

    Jia Xian Law & Shiplu Roy Chowdhury

  2. Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000, Kuala Lumpur, Malaysia

    Binti Haji Idrus Ruszymah

  3. Ear, Nose and Throat Consultant Clinic, Ampang Puteri Specialist Hospital, Ampang, Selangor, Malaysia

    Bin Saim Aminuddin

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  1. Jia Xian Law
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Correspondence to Binti Haji Idrus Ruszymah.

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Law, J.X., Chowdhury, S.R., Aminuddin, B.S. et al. Role of plasma-derived fibrin on keratinocyte and fibroblast wound healing. Cell Tissue Bank 18, 585–595 (2017). https://doi.org/10.1007/s10561-017-9645-2

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