Angiogenic Biomarkers and Healing of Living Cellular Constructs

• Published in: Journal of dental research 2011-04, Vol.90 (4), p.456-462
• Main Authors: Morelli, T., Neiva, R., Nevins, M.L., McGuire, M.K., Scheyer, E.T., Oh, T.-J., Braun, T.M., Nör, J.E., Bates, D., Giannobile, W.V.
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Angiogenesis; Angiogenesis Inducing Agents - analysis; Angiogenesis Inhibitors - analysis; Angiogenic Proteins - analysis; Angiogenin; Angiostatin; Angiostatins - analysis; Applied cell therapy and gene therapy; Biological and medical sciences; Biomarkers; Biomarkers - analysis; Biotechnology; Chemokine CXCL10 - analysis; Clinical trials; Cohort Studies; Collagen; Dentistry; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Feasibility Studies; Female; Fibroblast growth factor 2; Fibroblast Growth Factor 2 - analysis; Fibroblasts; Fibroblasts - transplantation; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Gingiva - transplantation; Gingival Crevicular Fluid - chemistry; Gingival Diseases - surgery; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - analysis; Growth factors; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Interleukin 8; Interleukin-8 - analysis; IP-10 protein; Keratinocytes - transplantation; Male; Medical sciences; Middle Aged; Miscellaneous; Mucosa; Non tumoral diseases; Otorhinolaryngology. Stomatology; Patients; Platelet-derived growth factor; Platelet-Derived Growth Factor - analysis; Platelet-derived growth factor BB; Proto-Oncogene Proteins c-sis; Reconstructive Surgical Procedures - methods; Research Reports; Ribonuclease, Pancreatic - analysis; Soft tissues; Studies; Surgery; Tissue Engineering; Tissue inhibitor of metalloproteinase 1; Tissue inhibitor of metalloproteinase 2; Tissue Inhibitor of Metalloproteinase-1 - analysis; Tissue Inhibitor of Metalloproteinase-2 - analysis; Tissue Scaffolds; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Ulcers; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - analysis; Wound healing; Wound Healing - physiology
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034510389334

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).