BACKGROUND: Fat grafting is an adjuvant that may improve the quality of radiation-damaged tissue. However, fat grafting for volume restoration in irradiated sites may be less effective because of a poorly vascularized fibrotic recipient bed. External volume expansion has emerged as a potential technique to prepare the recipient sites for improved survival of grafted fat. The authors previously demonstrated increased vasculature with external volume expansion stimulation of irradiated tissues. The authors now hypothesize that external volume expansion's improvements in recipient-site vascularity will increase the volume retention and quality of fat grafts in fibrotic irradiated sites. METHODS: Athymic mice were irradiated until development of chronic radiation injury. Then, the irradiated site was stimulated by external volume expansion (external volume expansion group), followed by subcutaneous fat grafting. Grafts in an irradiated site without external volume expansion stimulation (irradiated control group) and grafts in a healthy nonirradiated (nonirradiated control group) site were used as controls. All grafts were monitored for 8 weeks and evaluated both histologically and by micro-computed tomography for analysis of volume retention. RESULTS: Hyperspectral imaging confirmed a 25 percent decrease in vascularity of irradiated tissue (irradiated control group) compared with nonirradiated tissue (nonirradiated control group). Grafts in the irradiated control group retained 11 percent less volume than grafts in the nonirradiated control group. The experimental external volume expansion group achieved a 20 percent (p = 0.01) increase in retained graft volume compared with the irradiated control group. CONCLUSIONS: External volume expansion stimulation can mitigate the effects of irradiation at the recipient site and in turn help preserve fat graft volume retention. Possible mechanisms include increased vascularity, adipogenic conversion, and increased compliance of a fibrotic recipient site.

BACKGROUND: External volume expansion prepares recipient sites to improve outcomes of fat grafting. For patients receiving radiotherapy after mastectomy, results with external volume expansion vary, and the relationship between radiotherapy and expansion remains unexplored. Thus, the authors developed a new translational model to investigate the effects in chronic skin fibrosis after radiation exposure. METHODS: Twenty-four SKH1-E mice received 50 Gy of beta-radiation to each flank and were monitored until fibrosis developed (8 weeks). External volume expansion was then applied at -25 mmHg to one side for 6 hours for 5 days. The opposite side served as the control. Perfusion changes were assessed with hyperspectral imaging. Mice were euthanized at 5 (n = 12) and 15 days (n = 12) after the last expansion application. Tissue samples were analyzed with immunohistochemistry for CD31 and Ki67, Masson trichrome for skin thickness, and picrosirius red to analyze collagen composition. RESULTS: All animals developed skin fibrosis 8 weeks after radiotherapy and became hypoperfused based on hyperspectral imaging. Expansion induced edema on treated sides after stimulation. Perfusion was decreased by 13 percent on the expansion side (p < 0.001) compared with the control side for 5 days after stimulation. Perfusion returned to control-side levels by day 15. Dermal vasculature increased 38 percent by day 15 (p < 0.01) in expansion versus control. No difference was found in collagen composition. CONCLUSIONS: External volume expansion temporarily reduces perfusion, likely because of transient ischemia or edema. Together with mechanotransduction, these effects encourage a proangiogenic and proliferative environment in fibrotic tissue after radiotherapy in the authors' mouse model. Further studies are needed to assess these changes in fat graft retention.

PURPOSE: To evaluate the effect of the AeroForm (AirXpanders Inc, Palo Alto, CA) tissue expander on the dose distribution in a phantom from a simulated postmastectomy radiation treatment for breast cancer. METHODS AND MATERIALS: Experiments were conducted to determine the effect on the dose distribution with the metallic reservoir irradiated independently and with the entire AeroForm tissue expander placed on a RANDO phantom (The Phantom Laboratory, Salem, NY). The metallic reservoir was irradiated on a block of solid water with film at various depths ranging from 0 to 8.2 cm from the surface. The intact 400 cc AeroForm was inflated to full capacity and irradiated while positioned on a RANDO phantom, with 12 optically stimulated luminescent dosimeters (OSLDs) placed at clinically relevant expander-tissue interface points. RESULTS: Film dosimetry with the reservoir perpendicular to film reveals 40% transmission at a depth of 0.7 cm, which increases to 60% at a depth of 8.2 cm. In the parallel position, the results vary depending on which area under the reservoir is examined, indicating that the reservoir is not a uniformly dense object. Testing of the intact expander on the phantom revealed that the average percent difference (measured vs expected dose) was 2.7%, sigma = 6.2% with heterogeneity correction and 3.7%, sigma = 2.4% without heterogeneity correction. The only position where the OSLD readings were consistently higher than the calculated dose by > 5% was at position 1, just deep to the canister at the expander-phantom interface. At this position, the readings varied from 5.2% to 14.5%, regardless of heterogeneity correction. CONCLUSIONS: Film dosimetry demonstrated beam attenuation in the shadow of the metallic reservoir in the expander. This decrease in dose was not reproduced on the intact expander on the phantom designed to replicate a clinical setup. Inc.

Introduction: External Volume Expansion (EVE) treatment has gained popularity in breast reconstruction, enriching recipient sites for fat grafting. For patients receiving radiotherapy (XRT), results of EVE use vary, partly because the effects of EVE on irradiated tissue are not well understood. Based on our previous work with EVE and XRT, we developed a new translational model to investigate the effects of EVE in the setting of chronic radiation skin injury. Methods: Twenty-Eight SKH1-E mice received 50Gy of beta-radiation to each flank. Animals were monitored until chronic radiation fibrosis developed (8 weeks). EVE was then applied to one side for 6hrs on 5 consecutive days. The opposite side served as control. Hyperspectral Imaging (HSI) was used to assess perfusion changes before and after EVE. Mice were sacrificed at 5 days (n=14) and 15 days (n=14) after last application for histological analysis. Tissue samples were stained for vascularity (CD31) and collagen composition (Picro-Sirius red). Results: All animals developed skin fibrosis 8 weeks post-radiation, and changes in perfusion verified skin damage. EVE application induced edema on treated sides. Five days post-application, both sides were hypo-perfused as seen by HSI; with the EVE side 13% more ischemic than the untreated side (p<0.001). Perfusion returned to control side levels by day 15. Blood vessels increased 20% by day 5 in EVE versus control. Collagen composition showed no difference in scar index analysis. Conclusion: EVE temporarily augments radiation-induced hypo-perfusion, likely due to transient edema. Fibrosis remained unchanged after EVE, possibly accounting for the limited expansion seen in patients. It appears that EVE induces angiogenic effect but does not affect dermal collagen composition. Future efforts should focus on reducing fibrosis post radiation to allow EVE to achieve its full potential, to benefit irradiated patients.