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Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis.
Ann Surg 2009; 250(2):322-30AnnS

Abstract

INTRODUCTION

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.

Authors+Show Affiliations

Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19638916

Citation

Scherer, Saja Sandra, et al. "Poly-N-acetyl Glucosamine Nanofibers: a New Bioactive Material to Enhance Diabetic Wound Healing By Cell Migration and Angiogenesis." Annals of Surgery, vol. 250, no. 2, 2009, pp. 322-30.
Scherer SS, Pietramaggiori G, Matthews J, et al. Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis. Ann Surg. 2009;250(2):322-30.
Scherer, S. S., Pietramaggiori, G., Matthews, J., Perry, S., Assmann, A., Carothers, A., ... Orgill, D. P. (2009). Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis. Annals of Surgery, 250(2), pp. 322-30. doi:10.1097/SLA.0b013e3181ae9d45.
Scherer SS, et al. Poly-N-acetyl Glucosamine Nanofibers: a New Bioactive Material to Enhance Diabetic Wound Healing By Cell Migration and Angiogenesis. Ann Surg. 2009;250(2):322-30. PubMed PMID: 19638916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis. AU - Scherer,Saja Sandra, AU - Pietramaggiori,Giorgio, AU - Matthews,Jasmine, AU - Perry,Samuel, AU - Assmann,Anke, AU - Carothers,Adelaide, AU - Demcheva,Marina, AU - Muise-Helmericks,Robin C, AU - Seth,Arun, AU - Vournakis,John N, AU - Valeri,Robert C, AU - Fischer,Thomas H, AU - Hechtman,Herbert B, AU - Orgill,Dennis P, PY - 2009/7/30/entrez PY - 2009/7/30/pubmed PY - 2009/8/21/medline SP - 322 EP - 30 JF - Annals of surgery JO - Ann. Surg. VL - 250 IS - 2 N2 - INTRODUCTION: 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. SN - 1528-1140 UR - https://www.unboundmedicine.com/medline/citation/19638916/Poly_N_acetyl_glucosamine_nanofibers:_a_new_bioactive_material_to_enhance_diabetic_wound_healing_by_cell_migration_and_angiogenesis_ L2 - http://Insights.ovid.com/pubmed?pmid=19638916 DB - PRIME DP - Unbound Medicine ER -