Local delivery of antitumor necrosis factor-α through conjugation to hyaluronic acid: dosing strategies and early healing effects in a rat burn model.

J Burn Care Res 2015 Mar-Apr;36(2):e90-e101

From the Departments of *Biomedical Engineering and †Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania; and ‡McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pennsylvania.

The objective of this study was to measure dose-response effects of topical delivery of inhibitors of tumor necrosis factor-α (TNF-α) through conjugation to hyaluronic acid in a rat burn model to determine effects on inflammatory responses, burn progression, and early stages of healing. Monoclonal antibodies against TNF-α were conjugated to hyaluronic acid and applied topically in a rat partial-thickness burn model. Metrics of inflammatory responses and tissue necrosis were measured as well as the quantitative analysis of collagen composition and organization. The minimum effective conjugated antibody dose was found to be 100 μg with three applications 48 hours apart. Nonviable tissue thicknesses decreased with increasing dose and dose frequency. Free antibody retarded macrophage infiltration in the periphery but not at the surface, while the conjugated antibody was able to hinder macrophage infiltration at both the periphery and the surface. Quantification of collagen I and III staining ratios at days 4, 7, and 14 and quantitative image analysis of collagen organization at day 14 demonstrated differences between saline and conjugate treatment. This correlated with increases in re-epithelialization observed in conjugate-treated sites. Reductions in inflammatory markers and secondary tissue necrosis under treatment with the conjugates were understood in terms of differences in antibody transport compared to nonconjugated antibody. Differences in collagen composition and organization at Day 14 suggested that the reductions in inflammatory responses altered early healing responses. These results indicate anti-TNF-α conjugated to hyaluronic acid can be an effective treatment for reducing secondary necrosis and improving healing outcomes in burns.

Download full-text PDF

Source
http://dx.doi.org/10.1097/BCR.0000000000000140DOI Listing
November 2015
7 Reads
3 Citations
1.550 Impact Factor

Publication Analysis

Top Keywords

hyaluronic acid
16
burn model
12
inflammatory responses
12
infiltration periphery
8
periphery surface
8
rat burn
8
early healing
8
conjugated hyaluronic
8
analysis collagen
8
tissue necrosis
8
collagen composition
8
composition organization
8
conjugated antibody
8
organization day
8
macrophage infiltration
8
reductions inflammatory
8
necrosis factor-α
8
conjugation hyaluronic
8
necrosis
5
antibody
5

References

(Supplied by CrossRef)

Arturson et al.
Burns 1996

Beutler et al.
Annu Rev Immunol 1989

Schwacha et al.
J Surg Res 2010

Ming et al.
J Immunol 1987

Mori et al.
FASEB J 2002

Schabert et al.
J Manag Care Pharm 2013

Scheinfeld et al.
J Dermatolog Treat 2004

Alexis et al.
J Cutan Med Surg 2005

Friedrich et al.
J Biomed Mater Res A 2013

Voigt et al.
Wound Repair Regen 2012

Salbach et al.
J Mol Med (Berl) 2012

Similar Publications