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Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing.

Publication ,  Journal Article
Sun, G; Zhang, X; Shen, Y-I; Sebastian, R; Dickinson, LE; Fox-Talbot, K; Reinblatt, M; Steenbergen, C; Harmon, JW; Gerecht, S
Published in: Proceedings of the National Academy of Sciences of the United States of America
December 2011

Neovascularization is a critical determinant of wound-healing outcomes for deep burn injuries. We hypothesize that dextran-based hydrogels can serve as instructive scaffolds to promote neovascularization and skin regeneration in third-degree burn wounds. Dextran hydrogels are soft and pliable, offering opportunities to improve the management of burn wound treatment. We first developed a procedure to treat burn wounds on mice with dextran hydrogels. In this procedure, we followed clinical practice of wound excision to remove full-thickness burned skin, and then covered the wound with the dextran hydrogel and a dressing layer. Our procedure allows the hydrogel to remain intact and securely in place during the entire healing period, thus offering opportunities to simplify the management of burn wound treatment. A 3-week comparative study indicated that dextran hydrogel promoted dermal regeneration with complete skin appendages. The hydrogel scaffold facilitated early inflammatory cell infiltration that led to its rapid degradation, promoting the infiltration of angiogenic cells into the healing wounds. Endothelial cells homed into the hydrogel scaffolds to enable neovascularization by day 7, resulting in an increased blood flow significantly greater than treated and untreated controls. By day 21, burn wounds treated with hydrogel developed a mature epithelial structure with hair follicles and sebaceous glands. After 5 weeks of treatment, the hydrogel scaffolds promoted new hair growth and epidermal morphology and thickness similar to normal mouse skin. Collectively, our evidence shows that customized dextran-based hydrogel alone, with no additional growth factors, cytokines, or cells, promoted remarkable neovascularization and skin regeneration and may lead to novel treatments for dermal wounds.

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Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

December 2011

Volume

108

Issue

52

Start / End Page

20976 / 20981

Related Subject Headings

  • Wound Healing
  • Tissue Scaffolds
  • Skin Physiological Phenomena
  • Neovascularization, Physiologic
  • Microscopy, Electron, Scanning
  • Mice
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Dextrans
  • Burns
  • Animals
 

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Sun, G., Zhang, X., Shen, Y.-I., Sebastian, R., Dickinson, L. E., Fox-Talbot, K., … Gerecht, S. (2011). Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proceedings of the National Academy of Sciences of the United States of America, 108(52), 20976–20981. https://doi.org/10.1073/pnas.1115973108
Sun, Guoming, Xianjie Zhang, Yu-I Shen, Raul Sebastian, Laura E. Dickinson, Karen Fox-Talbot, Maura Reinblatt, Charles Steenbergen, John W. Harmon, and Sharon Gerecht. “Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing.Proceedings of the National Academy of Sciences of the United States of America 108, no. 52 (December 2011): 20976–81. https://doi.org/10.1073/pnas.1115973108.
Sun G, Zhang X, Shen Y-I, Sebastian R, Dickinson LE, Fox-Talbot K, et al. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proceedings of the National Academy of Sciences of the United States of America. 2011 Dec;108(52):20976–81.
Sun, Guoming, et al. “Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing.Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 52, Dec. 2011, pp. 20976–81. Epmc, doi:10.1073/pnas.1115973108.
Sun G, Zhang X, Shen Y-I, Sebastian R, Dickinson LE, Fox-Talbot K, Reinblatt M, Steenbergen C, Harmon JW, Gerecht S. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proceedings of the National Academy of Sciences of the United States of America. 2011 Dec;108(52):20976–20981.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

December 2011

Volume

108

Issue

52

Start / End Page

20976 / 20981

Related Subject Headings

  • Wound Healing
  • Tissue Scaffolds
  • Skin Physiological Phenomena
  • Neovascularization, Physiologic
  • Microscopy, Electron, Scanning
  • Mice
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Dextrans
  • Burns
  • Animals