Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis.
BACKGROUND
In several fields of surgery, the treatment of complicated tissue defects is an unsolved clinical problem. In particular, the use of tissue scaffolds has been limited by poor revascularization and integration. In this study, we developed a polymer, poly-N-acetyl-glucosamine (sNAG), with bioactive properties that may be useful to overcome these limitations.


OBJECTIVE
To develop a scaffold-like membrane with bioactive properties and test the biologic effects in vitro and in vivo in diabetic wound healing.


METHODS
In vitro, cells-nanofibers interactions were tested by cell metabolism and migration assays. In vivo, full thickness wounds in diabetic mice (n = 15 per group) were treated either with sNAG scaffolds, with a cellulosic control material, or were left untreated. Wound healing kinetics, including wound reepithelialization and wound contraction as well as microscopic metrics such as tissue growth, cell proliferation (Ki67), angiogenesis (PECAM-1), cell migration (MAP-Kinase), and keratinocyte migration (p 63) were monitored over a period of 28 days. Messenger RNA levels related to migration (uPAR), angiogenesis (VEGF), inflammatory response (IL-1beta), and extracellular matrix remodeling (MMP3 and 9) were measured in wound tissues.


RESULTS
sNAG fibers stimulated cell metabolism and the in vitro migratory activity of endothelial cells and fibroblasts. sNAG membranes profoundly accelerated wound closure mainly by reepithelialization and increased keratinocyte migration (7.5-fold), granulation tissue formation (2.8-fold), cell proliferation (4-fold), and vascularization (2.7-fold) compared with control wounds. Expression of markers of angiogenesis (VEGF), cell migration (uPAR) and ECM remodeling (MMP3, MMP9) were up-regulated in sNAG treated wounds compared with controls.


CONCLUSIONS
The key mechanism of the bioactive membranes is the cell-nanofiber stimulatory interaction. Engineering of bioactive materials may represent the clinical solution for a number of complex tissue defects.
Scherer
Saja Sandra
SS
Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Pietramaggiori
Giorgio
G
Matthews
Jasmine
J
Perry
Samuel
S
Assmann
Anke
A
Carothers
Adelaide
A
Demcheva
Marina
M
Muise-Helmericks
Robin C
RC
Seth
Arun
A
Vournakis
John N
JN
Valeri
Robert C
RC
Fischer
Thomas H
TH
Hechtman
Herbert B
HB
Orgill
Dennis P
DP
D020341:Absorbable Implants; D000117:Acetylglucosamine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012883:Skin Ulcer / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D054457:Tissue Scaffolds; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
C113831:poly-N-acetyl glucosamine; D000117:Acetylglucosamine