Bioactive peptide amphiphile nanofiber gels enhance burn wound healing

Situo Zhou; Akishige Hokugo; Mark McClendon; Zheyu Zhang; Reena Bakshi; Lixin Wang; Luis Andres Segovia; Kameron Rezzadeh; Samuel I Stupp; Reza Jarrahy

doi:10.1016/j.burns.2018.06.008

Bioactive peptide amphiphile nanofiber gels enhance burn wound healing

Burns. 2019 Aug;45(5):1112-1121. doi: 10.1016/j.burns.2018.06.008. Epub 2019 Apr 28.

Authors

Affiliations

¹ Regenerative Bioengineering and Repair (REBAR) Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Department of Burns and Reconstructive Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Regenerative Bioengineering and Repair (REBAR) Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ Simpson Querrey Institute , Northwestern University, Chicago, IL, USA.
⁴ Regenerative Bioengineering and Repair (REBAR) Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Department of Dentistry, Chengdu Women and Children's Central Hospital, Chengdu, Sichuan, China.
⁵ Simpson Querrey Institute , Northwestern University, Chicago, IL, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA; Department of Chemistry, Northwestern University, Evanston, IL, USA; Department of Medicine, Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
⁶ Regenerative Bioengineering and Repair (REBAR) Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: rjarrahy@mednet.ucla.edu.

PMID: 31043333
DOI: 10.1016/j.burns.2018.06.008

Abstract

Background: Burns are physically debilitating and potentially fatal injuries. The standard-of-care for burn wounds is the coverage with gauze dressings designed to minimize trauma to the regenerating epidermis and dermis during dressing changes. However, deep partial- and full-thickness burns always heal slowly when standard wound care alone is performed. We have previously reported that peptide amphiphile (PA) gels, pH-induced self-assembling nanostructured fibrous scaffolds, promote cell proliferation and have great potential in regenerative medicine for rapid repair of tissues. In this study, we hypothesized that the PA gels are capable of accelerating wound healing in burn injury.

Methods: Artificially generated thermally damaged fibroblasts and human umbilical vein endothelial cells were seeded onto the various PA nanofiber gels including bioactive and nonbioactive peptide sequences. Cell proliferation was assessed at different time points, and thermally damaged fibroblasts and HUVECs manifested increased proliferation with time when cultured with various PA gels. To determine in vivo effects, burn wounds of rats were treated with the bioactive Arg-Gly-Asp-Ser (RGDS)-modified gel that showed greater cell proliferation in vitro. The wound closure was observed, and skin samples were harvested for histologic evaluation.

Results: Cell proliferation using the RGDS-PA gel was significantly higher than that observed in other gels. The RGDS-PA gel significantly enhanced re-epithelialization during the burn wound healing process between days 7 and 28. Application of PA gels accelerates the recovery of deep partial-thickness burn wounds by stimulation of fibroblasts and the creation of an environment conducive to epithelial cell proliferation and wound closure.

Conclusions: This biomaterial represents a new therapeutic strategy to overcome current clinical challenges in the treatment of injuries resulting from burns.

Keywords: Nanofiber; Peptide amphiphile; Self-assembly; Thermally damaged cells; Wound healing.

MeSH terms

Animals
Burns / drug therapy*
Cell Proliferation / drug effects*
Fibroblasts / drug effects*
Gels*
Human Umbilical Vein Endothelial Cells
Humans
In Vitro Techniques
Nanofibers*
Oligopeptides / pharmacology*
Peptides / pharmacology
Platelet Aggregation Inhibitors / pharmacology*
Rats
Surface-Active Agents / pharmacology
Wound Healing / drug effects*

Substances

Gels
Oligopeptides
Peptides
Platelet Aggregation Inhibitors
Surface-Active Agents
arginyl-glycyl-aspartyl-serine