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Lyophilized Human Amnion Chorion Membrane Improves Scar Formation through Myofibroblast TGFB Expression
Jonathan P. Yasmeh MS, Hudson C. Kussie BS, Andrew C. Hostler BS, Maia Granoski BA, Eamonn McKenna BS, Abdelrahman M Alsharif, Jenne Stensland MS, Maria Gracia Mora Pinos MD, Maisam Jafri BS, Autumn Lester BS, Fidel Saenz BS, Katharina S. Fischer MD, Aaron C. Mason MD, Kellen Chen PhD, Geoffrey C. Gurtner MD
University of Arizona
2024-02-01
Presenter: Jonathan P. Yasmeh
Affidavit:
I certify that the abstract submitted by Jonathan represents all original work performed primarily by Jonathan. The conception and design of the study were envisioned primarily by myself and Dr. Kellen Chen.
Director Name: Geoffrey Gurtner
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction
Following cutaneous injury, chronic inflammation and dysregulated extracellular matrix formation (ECM) can result in hypertrophic scar (HTS). Here, we investigate whether a tri-layer lyophilized human amnion chorion membrane (LHACM) can regulate HTS.
Methods
We induced human-like HTS in mice by applying mechanical strain across incisional wounds. Full-thickness incisions were made on the dorsa, and LHACM (treatment) was placed subcutaneously. Mechanical loading devices were secured over the wounds and expanded by 2mm every other day for 14 days (strain). Groups were divided into no treatment+strain; no treatment+no strain; treatment+strain; treatment+no strain (n=5 each). HTS tissue was analyzed using Picrosirius Red and immunofluorescence staining, with ImageJ, Matlab, CurveAlign, and CTfire.
Results
Mechanical strain caused an average scar width of 1.21cm, which was significantly increased compared to 0.62cm non-strained wounds (p=0.0019). Treatment with subcutaneous LHCAM in mechanically strained and unstrained mice significantly reduced scar widths to 0.697cm (p=0.0325) and 0.548cm (p=0.0011) respectively. Analysis of ECM histology showed that treatment+strain elicited collagen fibers that were significantly less wide (p=<0.0001), less straight (p=<0.0001), and more aligned (p=0.0056).
Mechanical strain led to higher levels of TGFB signaling (p=0.0097), while treatment+strain significantly reduced TGFB signaling (p=0.0105). Treatment with and without strain significantly reduced myofibroblast expression (p=0.0304) compared to no treatment+strain. There was no effect on macrophages.
Conclusion
Mechanical strain across a wound increased scar width and elevated TGFB signaling. Subcutaneous treatment with LHACM had direct effects on scar width and collagen tissue architecture, which could be driven by expression of TGFB from myofibroblasts.
