Alexandra O Luby1, Alicia E Snider2, Gurjit S Mandair3, Kevin M Urlaub1, Jeremy V Lynn1, Noah S Nelson1, Alexis Donneys1, Russell E Ettinger4, Geoffrey C Gurtner5, David Kohn3, Steven R Buchman1. 1. From the Section of Plastic Surgery Craniofacial Research Laboratory, Department of Surgery, University of Michigan Health System, Ann Arbor, MI. 2. Department of Surgery, School of Medicine, University of South Carolina, Columbia, SC. 3. Department of Chemistry, University of Michigan Medical School, Ann Arbor, MI. 4. Division of Plastic Surgery, Department of Surgery, University of Washington, Seattle, WA. 5. Department of Surgery, Stanford University, Stanford, CA.
Abstract
BACKGROUND: Radiation therapy (XRT) induced dermal injury disrupts type I collagen architecture. This impairs cutaneous viscoelasticity, which may contribute to the high rate of complications in expander-based breast reconstruction with adjuvant XRT. The objective of this study was to further elucidate the mechanism of radiation-induced dermal injury and to determine if amifostine (AMF) or deferoxamine (DFO) mitigates type I collagen injury in an irradiated murine model of expander-based breast reconstruction. METHODS: Female Lewis rats (n = 20) were grouped: expander (control), expander-XRT (XRT), expander-XRT-AMF (AMF), and expander-XRT-DFO (DFO). Expanders were surgically placed. All XRT groups received 28 Gy of XRT. The AMF group received AMF 30 minutes before XRT, and the DFO group used a patch for delivery 5 days post-XRT. After a 20-day recovery period, skin was harvested. Atomic force microscopy and Raman spectroscopy were performed to evaluate type I collagen sheet organization and tissue compositional properties, respectively. RESULTS: Type I collagen fibril disorganization was significantly increased in the XRT group compared with the control (83.8% vs 22.4%; P = 0.001). Collagen/matrix ratios were greatly reduced in the XRT group compared with the control group (0.49 ± 0.09 vs 0.66 ± 0.09; P = 0.017). Prophylactic AMF demonstrated a marked reduction in type I collagen fibril disorganization on atomic force microscopy (15.9% vs 83.8%; P = 0.001). In fact, AMF normalized type I collagen organization in irradiated tissues to the level of the nonirradiated control (P = 0.122). Based on Raman spectroscopy, both AMF and DFO demonstrated significant differential protective effects on expanded-irradiated tissues. Collagen/matrix ratios were significantly preserved in the AMF group compared with the XRT group (0.49 ± 0.09 vs 0.69 ± 0.10; P = 0.010). β-Sheet/α-helix ratios were significantly increased in the DFO group compared with the XRT group (1.76 ± 0.03 vs 1.86 ± 0.06; P = 0.038). CONCLUSIONS: Amifostine resulted in a significant improvement in type I collagen fibril organization and collagen synthesis, whereas DFO mitigated abnormal changes in collagen secondary structure in an irradiated murine model of expander-based breast reconstruction. These therapeutics offer the ability to retain the native microarchitecture of type I collagen after radiation. Amifostine and DFO may offer clinical utility to reduce radiation induced dermal injury, potentially decreasing the high complication rate of expander-based breast reconstruction with adjuvant XRT and improving surgical outcomes.
BACKGROUND: Radiation therapy (XRT) induced dermal injury disrupts type I collagen architecture. This impairs cutaneous viscoelasticity, which may contribute to the high rate of complications in expander-based breast reconstruction with adjuvant XRT. The objective of this study was to further elucidate the mechanism of radiation-induced dermal injury and to determine if amifostine (AMF) or deferoxamine (DFO) mitigates type I collagen injury in an irradiated murine model of expander-based breast reconstruction. METHODS: Female Lewis rats (n = 20) were grouped: expander (control), expander-XRT (XRT), expander-XRT-AMF (AMF), and expander-XRT-DFO (DFO). Expanders were surgically placed. All XRT groups received 28 Gy of XRT. The AMF group received AMF 30 minutes before XRT, and the DFO group used a patch for delivery 5 days post-XRT. After a 20-day recovery period, skin was harvested. Atomic force microscopy and Raman spectroscopy were performed to evaluate type I collagen sheet organization and tissue compositional properties, respectively. RESULTS: Type I collagen fibril disorganization was significantly increased in the XRT group compared with the control (83.8% vs 22.4%; P = 0.001). Collagen/matrix ratios were greatly reduced in the XRT group compared with the control group (0.49 ± 0.09 vs 0.66 ± 0.09; P = 0.017). Prophylactic AMF demonstrated a marked reduction in type I collagen fibril disorganization on atomic force microscopy (15.9% vs 83.8%; P = 0.001). In fact, AMF normalized type I collagen organization in irradiated tissues to the level of the nonirradiated control (P = 0.122). Based on Raman spectroscopy, both AMF and DFO demonstrated significant differential protective effects on expanded-irradiated tissues. Collagen/matrix ratios were significantly preserved in the AMF group compared with the XRT group (0.49 ± 0.09 vs 0.69 ± 0.10; P = 0.010). β-Sheet/α-helix ratios were significantly increased in the DFO group compared with the XRT group (1.76 ± 0.03 vs 1.86 ± 0.06; P = 0.038). CONCLUSIONS: Amifostine resulted in a significant improvement in type I collagen fibril organization and collagen synthesis, whereas DFO mitigated abnormal changes in collagen secondary structure in an irradiated murine model of expander-based breast reconstruction. These therapeutics offer the ability to retain the native microarchitecture of type I collagen after radiation. Amifostine and DFO may offer clinical utility to reduce radiation induced dermal injury, potentially decreasing the high complication rate of expander-based breast reconstruction with adjuvant XRT and improving surgical outcomes.
Authors: Jessica Billig; Reshma Jagsi; Ji Qi; Jennifer B Hamill; Hyungjin M Kim; Andrea L Pusic; Edward Buchel; Edwin G Wilkins; Adeyiza O Momoh Journal: Plast Reconstr Surg Date: 2017-06 Impact factor: 4.730
Authors: Reshma Jagsi; Adeyiza O Momoh; Ji Qi; Jennifer B Hamill; Jessica Billig; Hyungjin M Kim; Andrea L Pusic; Edwin G Wilkins Journal: J Natl Cancer Inst Date: 2018-02-01 Impact factor: 13.506
Authors: A K Langton; H K Graham; J C McConnell; M J Sherratt; C E M Griffiths; R E B Watson Journal: Br J Dermatol Date: 2017-06-12 Impact factor: 9.302
Authors: Alicia E Snider; Jeremy V Lynn; Kevin M Urlaub; Alexis Donneys; Yekaterina Polyatskaya; Noah S Nelson; Russell E Ettinger; Geoffrey C Gurtner; Mark M Banaszak Holl; Steven R Buchman Journal: Ann Plast Surg Date: 2018-11 Impact factor: 1.539
Authors: Erin Mr Bigelow; Daniella M Patton; Ferrous S Ward; Antonio Ciarelli; Michael Casden; Andrea Clark; Robert W Goulet; Michael D Morris; Stephen H Schlecht; Gurjit S Mandair; Todd L Bredbenner; David H Kohn; Karl J Jepsen Journal: J Bone Miner Res Date: 2019-02-04 Impact factor: 6.741
Authors: Joseph A Ricci; Sherise Epstein; Adeyiza O Momoh; Samuel J Lin; Dhruv Singhal; Bernard T Lee Journal: J Surg Res Date: 2017-06-15 Impact factor: 2.192
Authors: Jose J Rodriguez; Theodore Kung; Yao Wang; Noah S Nelson; Yekaterina Polyatskaya; Sagar S Deshpande; Alexander R Zheutlin; Alexis Donneys; Steven R Buchman; Adeyiza O Momoh Journal: Ann Plast Surg Date: 2016-05 Impact factor: 1.539