Angiogenic biomarkers and healing of living cellular constructs.
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).
Department of Periodontics & Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
T
T
Morelli
R
R
Neiva
M L
ML
Nevins
M K
MK
McGuire
E T
ET
Scheyer
T-J
TJ
Oh
T M
TM
Braun
J E
JE
Nör
D
D
Bates
W V
WV
Giannobile
D043925:Angiogenesis Inducing Agents / Q000032:analysis; D020533:Angiogenesis Inhibitors / Q000032:analysis; D042501:Angiogenic Proteins / Q000032:analysis*; D043168:Angiostatins / Q000032:analysis; D000077214:Becaplermin; D015415:Biomarkers / Q000032:analysis; D054357:Chemokine CXCL10 / Q000032:analysis; D015331:Cohort Studies; D005240:Feasibility Studies; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005347:Fibroblasts / Q000637:transplantation*; D005500:Follow-Up Studies; D005881:Gingiva / Q000637:transplantation*; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D005882:Gingival Diseases / Q000601:surgery*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D015603:Keratinocytes / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D020574:Proto-Oncogene Proteins c-sis; D019651:Plastic Surgery Procedures / Q000379:methods; D012259:Ribonuclease, Pancreatic / Q000032:analysis; D023822:Tissue Engineering; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014945:Wound Healing / Q000502:physiology
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016209:Interleukin-8; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019716:Tissue Inhibitor of Metalloproteinase-2; D000077214:Becaplermin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D043168:Angiostatins; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
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