Sage Journals: Discover world-class research

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).

Keywords

tissue engineering gingival recession regenerative medicine wound repair regeneration angiogenesis clinical trial

Get full access to this article

View all access options for this article.

References

Chirco

Liu

Jung

Kim

(2006). Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev 25:99-113.

Cooke

Sarment

Whitesman

Miller

Jin

Lynch

. (2006). Effect of rhPDGF-BB delivery on mediators of periodontal wound repair. Tissue Eng 12:1441-1450.

Falabella

Schachner

Valencia

Eaglstein

(1999). The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa. Arch Dermatol 135:1219-1222.

Falanga

Margolis

Alvarez

Auletta

Maggiacomo

Altman

. (1998). Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol 134:293-300.

Fivenson

Scherschun

Choucair

Kukuruga

Young

Shwayder

(2003). Graftskin therapy in epidermolysis bullosa. J Am Acad Dermatol 48:886-892.

Giannobile

Lynch

Denmark

Paquette

Fiorellini

Williams

(1995). Crevicular fluid osteocalcin and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as markers of rapid bone turnover in periodontitis. A pilot study in beagle dogs. J Clin Periodontol 22:903-910.

Griffiths

Ojeh

Livingstone

Price

Navsaria

(2004). Survival of Apligraf in acute human wounds. Tissue Eng 10:1180-1195.

Izumi

Feinberg

Iida

Yoshizawa

(2003). Intraoral grafting of an ex vivo produced oral mucosa equivalent: a preliminary report. Int J Oral Maxillofac Surg 32:188-197.

Koch

Polverini

Kunkel

Harlow

. (1992). Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258(5089):1798-1801.

10.

Kumar

Staton

Cross

Reed

Brown

(2009). Angiogenesis, vascular endothelial growth factor and its receptors in human surgical wounds. Br J Surg 96:1484-1491.

11.

Dubey

Varney

Dave

Singh

(2003). IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol 170:3369-3376.

12.

McGuire

Nunn

(2005). Evaluation of the safety and efficacy of periodontal applications of a living tissue-engineered human fibroblast-derived dermal substitute. I. Comparison to the gingival autograft: a randomized controlled pilot study. J Periodontol 76:867-880.

13.

McGuire

Scheyer

Nunn

Lavin

(2008). A pilot study to evaluate a tissue-engineered bilayered cell therapy as an alternative to tissue from the palate. J Periodontol 79:1847-1856.

14.

McGuire

Scheyer

Nevins

Neiva

Cochran

Mellonig

. (2011). Living cellular construct for the treatment of mucogingival defects: results from a randomized, within-patient, controlled trial. J Periodontol (manuscript in review).

15.

Nissen

Polverini

Koch

Volin

Gamelli

DiPietro

(1998). Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 152: 1445-1452.

16.

Osborne

Schmid

(2002). Epidermal-dermal interactions regulate gelatinase activity in Apligraf, a tissue-engineered human skin equivalent. Br J Dermatol 146:26-31.

17.

Sabolinski

Alvarez

Auletta

Mulder

Parenteau

(1996). Cultured skin as a ‘smart material’ for healing wounds: experience in venous ulcers. Biomaterials 17:311-320.

18.

Sakai

Ohshima

Sugano

Otsuka

Ito

(2006). Profiling the cytokines in gingival crevicular fluid using a cytokine antibody array. J Periodontol 77:856-864.

19.

Stetler-Stevenson

(2008). Tissue inhibitors of metalloproteinases in cell signaling: metalloproteinase-independent biological activities. Sci Signal 1(27):re6.

20.

Stetler-Stevenson

Seo

(2005). TIMP-2: an endogenous inhibitor of angiogenesis. Trends Mol Med 11:97-103.

21.

Szpaderska

Walsh

Steinberg

DiPietro

(2005). Distinct patterns of angiogenesis in oral and skin wounds. J Dent Res 84: 309-314.

22.

Veves

Falanga

Armstrong

Sabolinski

(2001). Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial. Diabetes Care 24:290-295.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.73 MB

Angiogenic Biomarkers and Healing of Living Cellular Constructs

Abstract

Keywords

Get full access to this article

References

Supplementary Material