Reduction of burn progression with topical delivery of (antitumor necrosis factor‐α)‐hyaluronic acid conjugates

Abstract

In this study, we explored whether topical application of antibodies targeting tumor necrosis factor‐α (TNF‐α) or interleukin‐6 (IL‐6) conjugated to hyaluronic acid (HA) could reduce the extension of necrosis by modulating inflammation locally in a partial‐thickness rat burn model. Partial‐thickness to deep partial‐thickness burn injuries present significant challenges in healing, as these burns often progress following the initial thermal insult, resulting in necrotic expansion and increased likelihood of secondary complications. Necrotic expansion is driven by a microenvironment with elevated levels of pro‐inflammatory mediators, and local neutralization of these using antibody conjugates could reduce burn progression. Trichrome‐stained tissue sections indicated the least necrotic tissue in (anti‐TNF‐α)‐HA‐treated sites, while (anti‐IL‐6)‐HA‐treated sites displayed similar outcomes to saline controls. This was confirmed by vimentin immunostaining, which demonstrated that HA treatment alone reduced burn progression by nearly 30%, but (anti‐TNF‐α)‐HA reduced it by approximately 70%. At all time points, (anti‐TNF‐α)‐HA‐treated sites showed reduced tissue levels of IL‐1β compared to controls, suggesting inhibition of a downstream mediator of inflammation. Decreased macrophage infiltration in (anti‐TNF‐α)‐HA‐treated sites compared to controls was elucidated by immunohistochemical staining of macrophages, suggesting a reduction in overall inflammation in all time points. These results suggest that local targeting of TNF‐α may be an effective strategy for preventing progression of partial‐thickness burns.

3,4-Methylenedioxy-β-Nitrostyrene Ameliorates Experimental Burn Wound Progression by Inhibiting the NLRP3 Inflammasome Activation

“…1,5,36,37 Previous studies have emphasized the importance of proinflammatory cytokines from the interleukin-1 family, particularly interleukin-1β and interleukin-18, in mediating inflammation after burn. 38,39 Moreover, there have been successful attempts at using interleukin-1β-or interleukin-18-antagonizing drugs to treat inflammatory diseases such as rheumatoid arthritis and gout.…”

Current concepts on burn wound conversion—A review of recent advances in understanding the secondary progressions of burns

“…One such target is TNF-α, a cell signaling protein that regulates inflammation and is observed at high levels in the burn wound microenvironment [56]. Sun et al demonstrate that topical antibodies to TNF-α conjugated with hyaluronic acid (HA) reduce levels of downstream inflammatory mediators, decrease macrophage infiltration, and lessen secondary necrotic expansion of tissues [57].…”

“…IL-6 is elevated in burn patients [59], and plays a role in cytotoxic T-cell differentiation and T-cell proliferation [56]. Antibodies to IL-6, however, did not reduce burn progression compared to controls [10, 36, 60], suggesting that TNF-α, a more upstream cytokine, may play a more significant role in mediating inflammation in the burn wound environment.…”

Hyaluronic acid covers in burn treatment: a systematic review

“…When hyaluronic acid is applied in wounds, there is improved water retention, which favors a suitable environment for the formation of collagen and elastin, and allows the cells to proliferate and differentiate, accelerating the healing process (31) . Furthermore, the anti-inflammatory properties of hyaluronic acid influence the healing, preventing the conversion of wound (32)(33) and formation of hypertrophic scars or keloids (34) . Another relevant aspect for the application of hyaluronic acid is the fact of biomaterial being a non-immunogenic substance.…”