Lynday Stapleton, MS

August 2019

Picture of a dissected bovine heart 4 weeks after initial surgery. It was treated with hydrogel during the initial surgery and looks as if it was never operated on (no adhesions present).

Picture is of a bovine heart that was untreated (adhesions present).

 

Lyndsay Stapleton, MS, is a recent graduate and alumni of a Bioengineering PhD at Stanford University.  The Stanford Bio-X Graduate Fellowships offer PhD candidates funding independent of any one lab or grant, freeing recipients to pursue interdisciplinary research and to work with multiple mentors. The Stanford Interdisciplinary Graduate Fellowship (SIGF) Program is a competitive, university-wide program that awards three-year fellowships to outstanding doctoral students engaged in interdisciplinary research. The SIGF supports Stanford doctoral students in undertaking novel, cutting-edge research and pursuing questions that cross traditional disciplinary boundaries.

Lyndsay recently published in Nature Biomedical Engineering, titled "Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier" under Dr. Joseph Woo's lab, guidance, and research.

The research in summary includes "Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer–nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions."

Lyndsay became interested in adhesion research, as adhesions remain a major surgical challenge during all re-operation surgeries for patients.  Adhesions are fibrous bands of scar tissue that form in between internal tissues and organs - essentially wound healing where you do not want healing to occur.

This prompted her to investigate the current research and gap in research, investigation and advancement with adhesion surgery.  Lyndsay was a prime candidate for this research due to her ability to collaborate with her interest in both the Cardiac Surgery and Bioengineering departments.  She was able to use advanced models and tap into the resources from each arena.

Lyndsay felt very privileged being a part of Dr. Woo's lab. "I was able to observe a re-operation surgery where a patient had cardiac adhesions from a prior operation. Another reason why working in Dr. Woo's lab is such a great opportunity, with the ability to dream up a project and also see it’s barrios firsthand." Once a pathway was uncovered as a possible solution to this problem, Lyndsay and her team extensively studied the technology to assess its potential for this cardiac application. As Lyndsay reflected, some challenges that she was able to overcome during this project which occurred were "logistical challenges implementing the bypass protocol, but, with all of the talented cardiothoracic surgeons in the department, once we were able to get a protocol established we were able to easily utilize large animal cardiac bypass, as this is a routine procedure in the Woo lab."

The models used in this research study were used to most accurately simulate human cardiac surgery, in order to produce clinically relevant outcomes.  This research adhesion model performed heart and lung bypass on large animal models, specifically sheep, in order to closely mimic human cardiac surgery.  Lyndsay was very attracted to this project and research in preclinical large animal surgery, stating that it is "very exciting because they closely resemble the human case and took us one step closer to potential human translation."

Lyndsay and the Woo lab were able to utilize some exciting new technology during this research, including a novel, supramolecular polymer nanoparticle hydrogel as our adhesion barrier. They found that application of this hydrogel adhesion barrier significantly reduced the presence of adhesions in both small and large animal cardiac adhesion models, including preclinical models of cardiac bypass.

The next step for animal to potential human translation is to understand the long-term safety implications of this product as well as optimize the hydrogel formulation for maximal adhesion prevention.  There is still much research to be done before human testing can occur, but this research brings us one step closer.

Lyndsay was an active member of Dr. Joseph Woo lab for 5 years and was attracted to join because of the interdisciplinary opportunities the Woo lab offers.  Lyndsay recently graduated and is now working as a Manager of Strategy and Operations at a BioTech Company.  Lyndsay felt that one of her greatest successes was publication of this Nature paper.  She is proud of her time while "working for Dr. Woo has been/was an honor and a privilege. He offers so many opportunities for his students to work on projects that have the great translational impact. His lab really focuses on taking research from the bench to the bedside!"

You can read the full Nature Biomedical Engineering, titled "Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier."

Lindsay Stapleton