PURPOSE: Surgery within radiated tissue is associated with increased complication rates. It is hypothesized that impaired wound healing may result from aberrant inflammatory responses that occur in previously radiated tissues. Previous work has demonstrated that the topical application of naturally occurring antigen α-gal (Galα1-3Galβ1-(3)4GlcNAc-R) nanoparticles (AGNs) within wounds accelerates macrophage recruitment and subsequent healing in both normal and diabetic wounds. Herein, we hypothesize that application of this antigen would similarly enhance wound healing in irradiated tissues. METHODS: To simulate human physiology, α-1,3-galactosyltransferase knockout (KO) mice were exposed to the antigen to produce anti-α-gal antibodies (anti-Gal). Ten days prior to wounding, the dorsal skin was irradiated with 1 session of 40 Gy. Bilateral dorsal 6-mm splinted full-thickness wounds were created within the radiated skin and treated with 50 µL of AGNs (50 mg/mL) immediately after wounding and again on postoperative day 1. A control KO group underwent similar irradiation and wounding protocols but was treated with phosphate-buffered saline (PBS) vehicle. Wild-type (WT) mice, which do not produce anti-Gal, went through the same irradiation and wounding. RESULTS: Histologic analysis demonstrated enhanced epithelial migration in the radiated/AGN-treated KO wounds, which was significantly elevated in comparison to radiated/PBS-treated KO wounds beginning by day 15 and continuing until the end of the study (p < 0.01). In WT mice, treatment with AGNs showed no effect on epithelial migration. CONCLUSIONS: Topical application of AGNs onto irradiated wounds significantly ameliorates the delayed wound healing classically seen in radiated skin and results in faster wound closure with only transient application.
PURPOSE: Surgery within radiated tissue is associated with increased complication rates. It is hypothesized that impaired wound healing may result from aberrant inflammatory responses that occur in previously radiated tissues. Previous work has demonstrated that the topical application of naturally occurring antigen α-gal (Galα1-3Galβ1-(3)4GlcNAc-R) nanoparticles (AGNs) within wounds accelerates macrophage recruitment and subsequent healing in both normal and diabetic wounds. Herein, we hypothesize that application of this antigen would similarly enhance wound healing in irradiated tissues. METHODS: To simulate human physiology, α-1,3-galactosyltransferase knockout (KO) mice were exposed to the antigen to produce anti-α-gal antibodies (anti-Gal). Ten days prior to wounding, the dorsal skin was irradiated with 1 session of 40 Gy. Bilateral dorsal 6-mm splinted full-thickness wounds were created within the radiated skin and treated with 50 µL of AGNs (50 mg/mL) immediately after wounding and again on postoperative day 1. A control KO group underwent similar irradiation and wounding protocols but was treated with phosphate-buffered saline (PBS) vehicle. Wild-type (WT) mice, which do not produce anti-Gal, went through the same irradiation and wounding. RESULTS: Histologic analysis demonstrated enhanced epithelial migration in the radiated/AGN-treated KO wounds, which was significantly elevated in comparison to radiated/PBS-treated KO wounds beginning by day 15 and continuing until the end of the study (p < 0.01). In WT mice, treatment with AGNs showed no effect on epithelial migration. CONCLUSIONS: Topical application of AGNs onto irradiated wounds significantly ameliorates the delayed wound healing classically seen in radiated skin and results in faster wound closure with only transient application.
Authors: Johannes Schindelin; Ignacio Arganda-Carreras; Erwin Frise; Verena Kaynig; Mark Longair; Tobias Pietzsch; Stephan Preibisch; Curtis Rueden; Stephan Saalfeld; Benjamin Schmid; Jean-Yves Tinevez; Daniel James White; Volker Hartenstein; Kevin Eliceiri; Pavel Tomancak; Albert Cardona Journal: Nat Methods Date: 2012-06-28 Impact factor: 28.547
Authors: Scott Tyldesley; Geoff Delaney; Farshad Foroudi; Lisa Barbera; Marc Kerba; William Mackillop Journal: Int J Radiat Oncol Biol Phys Date: 2010-06-03 Impact factor: 7.038
Authors: Hendrik Lintel; Darren B Abbas; Christopher V Lavin; Michelle Griffin; Jason L Guo; Nicholas Guardino; Andrew Churukian; Geoffrey C Gurtner; Arash Momeni; Michael T Longaker; Derrick C Wan Journal: J Transl Med Date: 2022-06-17 Impact factor: 8.440