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Angiogenic biomarkers and healing of living cellular constructs.

ABSTRACT: The use of intra-oral soft-tissue-engineered devices has demonstrated potential for oral mucosa regeneration. The aim of this study was to investigate the temporal expression of angiogenic biomarkers during wound healing of soft tissue reconstructive procedures comparing living cellular constructs (LCC) with autogenous free gingival grafts. Forty-four human participants bilaterally lacking sufficient zones of attached keratinized gingiva were randomly assigned to soft tissue surgery plus either LCC or autograft. Wound fluid samples were collected at baseline and weeks 1, 2, 3, and 4 post-operatively and analyzed for a panel of angiogenic biomarkers: angiogenin (ANG), angiostatin (ANT), PDGF-BB, VEGF, FGF-2, IL-8, TIMP-1, TIMP-2, GM-CSF, and IP-10. Results demonstrated a significant increase in expression of ANT, PDGF-BB, VEGF, FGF-2, and IL-8 for the LCC group over the autograft group at the early stages of wound repair. Although angiogenic biomarkers were modestly elevated for the LCC group, no clinical correlation with wound healing was found. This human investigation demonstrates that, during early wound-healing events, expression of angiogenic-related biomarkers is up-regulated in sites treated with LCC compared with autogenous free gingival grafts, which may provide a safe and effective alternative for regenerating intra-oral soft tissues (ClinicalTrials.gov number, NCT01134081).

SUBMITTER: Morelli T

PROVIDER: S-EPMC3144125 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Angiogenic biomarkers and healing of living cellular constructs.

Morelli T T Neiva R R Nevins M L ML McGuire M K MK Scheyer E T ET Oh T-J TJ Braun T M TM Nör J E JE Bates D D Giannobile W V WV

Journal of dental research 20110119 4

The use of intra-oral soft-tissue-engineered devices has demonstrated potential for oral mucosa regeneration. The aim of this study was to investigate the temporal expression of angiogenic biomarkers during wound healing of soft tissue reconstructive procedures comparing living cellular constructs (LCC) with autogenous free gingival grafts. Forty-four human participants bilaterally lacking sufficient zones of attached keratinized gingiva were randomly assigned to soft tissue surgery plus either ...[more]

PMID: 21248359

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Project description:Modular tissue engineering is a method of building vascularized tissue-engineered constructs. Submillimeter-sized collagen pieces (modules) coated with a layer of endothelial cells (EC; vascular component), and with embedded functional cells, are self-assembled into a larger, three-dimensional tissue. In this study, we examined the use of developmental endothelial locus-1 (Del-1), an extracellular matrix protein with proangiogenic properties, as a means of tipping the angiogenic balance in human umbilical vein endothelial cells incorporated in modular tissue-engineered constructs. The motivation was to enhance the vascularization of these constructs upon transplantation in vivo, in this case, without the use of exogenous mesenchymal stromal cells. EC were transduced using a lentiviral construct to overexpress Del-1. The Del-1 EC formed more sprouts in a fibrin gel sprouting assay in vitro compared with eGFP (control) transduced EC, as expected. Del-1 EC had a distinct profile of gene expression (upregulation of matrix metalloproteinase-9 [MMP-9], urokinase-type plasminogen activator [uPA/PLAU], vascular endothelial growth factor [VEGF-A], and intercellular adhesion molecule-1 [ICAM-1]; downregulation of angiopoietin-2 [Ang2]), also supporting the notion of "tipping the angiogenic balance". On the other hand, contrary to our expectations, when Del-1 EC-coated modules were implanted subcutaneously in a severe combined immunodeficient/beige animal model, the proangiogenic effect of Del-1 was less remarkable. There was only a small increase in the number of blood vessels formed in Del-1 implants compared with the eGFP implants, and only few blood vessels formed at the implant site in both cases. This was presumed due to limited EC survival after transplantation. We speculate that if we could improve EC survival in our study (for example, by adding other prosurvival factors or supporting cells), we would see a greater Del-1-induced angiogenic benefit in vivo as a consequence of increased Del-1 secretion by a higher number of surviving cells.

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Angiogenic biomarkers and healing of living cellular constructs.

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Angiogenic biomarkers and healing of living cellular constructs.

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