Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing
Abstract Background Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and eve...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Biological Procedures Online |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12575-023-00227-w |
| _version_ | 1797350102468132864 |
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| author | Edita Aksamitiene Ryan N. Heffelfinger Jan B. Hoek Edmund deAzevedo Pribitkin |
| author_facet | Edita Aksamitiene Ryan N. Heffelfinger Jan B. Hoek Edmund deAzevedo Pribitkin |
| author_sort | Edita Aksamitiene |
| collection | DOAJ |
| description | Abstract Background Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. Our goal was to provide a step-by-step methodological protocol for creating an alternative standardized, more economical, and transferable pre-clinical animal research model of excisional full-thickness wound healing following a simulated autologous tissue transfer which includes the primary ischemia, reperfusion, and secondary ischemia events with the latter mimicking flap salvage procedure. Results Unlike in the most frequently used classical unilateral McFarlane’s caudally based dorsal random pattern skin flap model, in the herein described bilateral epigastric fasciocutaneous advancement flap (BEFAF) model, one flap heals under normal and a contralateral flap—under perturbed conditions or both flaps heal under conditions that vary by one within-subjects factor. We discuss the advantages and limitations of the proposed experimental approach and, as a part of model validation, provide the examples of its use in laboratory rat (Rattus norvegicus) axial pattern flap healing studies. Conclusions This technically challenging but feasible reconstructive surgery model eliminates inter-subject variability, while concomitantly minimizing the number of animals needed to achieve adequate statistical power. BEFAFs may be used to investigate the spatiotemporal cellular and molecular responses to complex tissue injury, interventions simulating clinically relevant flap complications (e.g., vascular thrombosis) as well as prophylactic, therapeutic or surgical treatment (e.g., flap delay) strategies in the presence or absence of confounding risk factors (e.g., substance abuse, irradiation, diabetes) or favorable wound-healing promoting activities (e.g., exercise). Detailed visual instructions in BEFAF protocol may serve as an aid for teaching medical or academic researchers basic vascular microsurgery techniques that focus on precision, tremor management and magnification. Graphical Abstract |
| first_indexed | 2024-03-08T12:39:58Z |
| format | Article |
| id | doaj.art-06406f6dc8584cc689f5d7ddffdd781b |
| institution | Directory Open Access Journal |
| issn | 1480-9222 |
| language | English |
| last_indexed | 2024-03-08T12:39:58Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Procedures Online |
| spelling | doaj.art-06406f6dc8584cc689f5d7ddffdd781b2024-01-21T12:10:47ZengBMCBiological Procedures Online1480-92222024-01-0126113710.1186/s12575-023-00227-wStandardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap HealingEdita Aksamitiene0Ryan N. Heffelfinger1Jan B. Hoek2Edmund deAzevedo Pribitkin3Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson UniversityDepartment of Otolaryngology – Head and Neck Surgery, Thomas Jefferson UniversityDepartment of Pathology, Anatomy and Cell Biology, Thomas Jefferson UniversityDepartment of Otolaryngology – Head and Neck Surgery, Thomas Jefferson UniversityAbstract Background Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. Our goal was to provide a step-by-step methodological protocol for creating an alternative standardized, more economical, and transferable pre-clinical animal research model of excisional full-thickness wound healing following a simulated autologous tissue transfer which includes the primary ischemia, reperfusion, and secondary ischemia events with the latter mimicking flap salvage procedure. Results Unlike in the most frequently used classical unilateral McFarlane’s caudally based dorsal random pattern skin flap model, in the herein described bilateral epigastric fasciocutaneous advancement flap (BEFAF) model, one flap heals under normal and a contralateral flap—under perturbed conditions or both flaps heal under conditions that vary by one within-subjects factor. We discuss the advantages and limitations of the proposed experimental approach and, as a part of model validation, provide the examples of its use in laboratory rat (Rattus norvegicus) axial pattern flap healing studies. Conclusions This technically challenging but feasible reconstructive surgery model eliminates inter-subject variability, while concomitantly minimizing the number of animals needed to achieve adequate statistical power. BEFAFs may be used to investigate the spatiotemporal cellular and molecular responses to complex tissue injury, interventions simulating clinically relevant flap complications (e.g., vascular thrombosis) as well as prophylactic, therapeutic or surgical treatment (e.g., flap delay) strategies in the presence or absence of confounding risk factors (e.g., substance abuse, irradiation, diabetes) or favorable wound-healing promoting activities (e.g., exercise). Detailed visual instructions in BEFAF protocol may serve as an aid for teaching medical or academic researchers basic vascular microsurgery techniques that focus on precision, tremor management and magnification. Graphical Abstracthttps://doi.org/10.1186/s12575-023-00227-wExcisional wound healingBilateral flapPedicled flapFasciocutaneous flapSuperficial inferior epigastric vesselsAxial pattern flap survival |
| spellingShingle | Edita Aksamitiene Ryan N. Heffelfinger Jan B. Hoek Edmund deAzevedo Pribitkin Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing Biological Procedures Online Excisional wound healing Bilateral flap Pedicled flap Fasciocutaneous flap Superficial inferior epigastric vessels Axial pattern flap survival |
| title | Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing |
| title_full | Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing |
| title_fullStr | Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing |
| title_full_unstemmed | Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing |
| title_short | Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing |
| title_sort | standardized pre clinical surgical animal model protocol to investigate the cellular and molecular mechanisms of ischemic flap healing |
| topic | Excisional wound healing Bilateral flap Pedicled flap Fasciocutaneous flap Superficial inferior epigastric vessels Axial pattern flap survival |
| url | https://doi.org/10.1186/s12575-023-00227-w |
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