Basic Science and Translational Research

Research studies conducted by staff and residents use rigorous procedures and cutting-edge technologies
that allow us to be leaders in new and advanced methods, techniques, and approaches.

OVERVIEW

LSU Plastic Surgery’s offers a full research pipeline from the basic sciences, to translational studies, to prospective, double-blinded randomized controlled trials. Residents and medical students participate as their interests, time, experience, and motivation allow. Major basic science and translational research areas include the following:

1. Microphysiological Systems of Breast Cancer

2. Vitamin D Insufficiency in COVID-19

3. Surgical Approaches to Pyoderma Gangrenosum

4. Regenerative Approaches to Limb Salvage

5. Incisional Hernia Prevention and Treatment

6. Advances in Breast Reconstruction

7. Diseases of White Adipose Tissue

Microphysiological Systems of Breast Cancer (BC-MPS)

Developed in Dr. Lau’s tissue engineering lab, BC-MPS combines insights from fat grafting, experience with thermoresponsive tissue culture substrates, and prior research involving human adipose tissues and pluripotent stem cells. BC-MPS transfers primary human breast tissue (HBT) from patients directly into tissue culture, where they remain alive and physiologically stable for at least 8 weeks. By seeding HBT with BC cell lines, we can produce powerful BC-MPS to study slow but critical phenomena that were previously inaccessible, including the hallmark processes of tumor microenvironment (TME) remodeling and BC-HBT metabolic crosstalk. This program has won multiple, competitive grants including from the Southeastern Society of Plastic Surgeons and an LSU system-wide health disparities in breast cancer grant; the technology has been patented; and a commercial development is being pursued in parallel with extramural funding opportunities. Their pilot study data were recently presented at the 2019 Cell Symposia: Hallmarks of Cancer in Seattle, WA.

Vitamin D Insufficiency in COVID-19

Risk factors for severe COVID-19 include hypertension, obesity, diabetes, age > 65 years, and African American ancestry. A unifying mechanism that links these risk factors to patients’ divergent outcomes remains elusive. Recent, epidemiological studies have recently suggested a link between vitamin D insufficiency (VDI) and COVID-19 severity. Dr. Lau’s research team, in a pilot study in New Orleans, found that 85% of COVID-19 ICU patients had VDI, vs. 57.1% in regular inpatients, vs. 30-40% in the general population. A larger, more rigorous study is under peer review. On the strength of these data, our team is developing a multi-center, prospective, randomized controlled trial to study the efficacy of early anti-platelet therapy and vitamin D supplementation in preventing COVID-19 hospitalizations (the LEAD COVID-19 Trial). Donations to help support this trial can be made through the LSU Health Foundation, a non-profit that supports LSU research efforts.

Surgical Approaches to Pyoderma Gangrenosum (PG)

PG is a rare but devastating disease of chronic, painful wounds marked pathergy, a process wherein tissue trauma worsens the wounds. Because of pathergy, these wounds cannot be surgically debrided. A multidisciplinary research team involving plastic surgery and dermatology found that by surgically debriding PG wounds and placing placenta-derived tissues (PDT), the clinical and molecular signatures of these wounds are rest, allowing for wound closure using split-thickness skin grafts. This is a dramatic breakthrough for the local control of PG, and indeed, their work has won multiple awards including Best Paper at the 2019 meeting of the Louisiana Chapter of American College of Physicians and the 2019 Medicine Research Day at UMCNO, and has been presented at national and international burn and wound care conferences. A manuscript is under preparation.

This research program, co-led by Dr. Lau and our resident Dr. Aran Yoo, is now focused on characterizing the pathophysiology of PG so that targeted, systemic therapies can be designed.

Regenerative Approaches to Limb Salvage

Extremity wounds with osseous, tendon, or joint exposures continue to be a reconstructive challenge. As a key component of limb salvage (LS), soft tissue reconstruction is necessary to avoid osteomyelitis and tendon or joint rupture, which would result in disability or amputation. Presently, the dominant LS paradigm employs the reconstructive elevator wherein flap-based LS (fLS) is the recommended first-line treatment paradigm. This paradigm developed due to the significantly higher failure rates for the lower rungs of the reconstructive ladder, such as skin grafts and local flaps. However, fLS is resource-intensive and expensive. Dr. Lau’s LS research team developed a novel, regenerative limb salvage (rLS) technique using dehydrated human amnion/chorion membrane (dHACM). In our pilot experience, 86% of adult rLS patients were successfully reconstructed. On the strength of this data, a prospective, randomized controlled trial was completed (manuscript in process), and a collaboration with Walter Reed/USUHS has been established. This technique has been successfully applied in pediatric patients, as reported in the news; a manuscript demonstrating the safety and efficacy of pediatric rLS is currently under peer review.

Incisional Hernias: Prevention, Health Disparities, and Treatment

In 2018, Dr. Lau assembled a multidisciplinary team to tackle a longstanding surgical complication: incisional hernias (IH). The overall goal was to identify new, safe, and effective approaches to prevent IH. From a research perspective, this project spanned the treatment development pipeline from animal models to human clinical trials. Starting with a validated, rodent model of acute IH, we demonstrated that placenta-derived tissues (PDT) could reduce IH by 65%, and presented our findings at the 2018 American College of Surgeons Clinical Congress. In a pilot study of high-risk patients, we found even greater efficacy. On the strength of these data, we proposed and received funding for a prospective, double-blinded, randomized controlled trial to study the efficacy of PDT in IH prophylaxis (the NO HERNIA Trial). Due to COVID-19, the trial’s start was delayed but enrollment is now ongoing.

From a health disparities perspective, not much was known specifically about IH. Our newest publication, which won a Gold Medal Award at the 2020 Southeastern Surgical Congress, used a national database to identify health disparities in the way these patients present with hernia-related problems (urgently vs non-urgently). Older, female, non-white, and uninsured patients were significantly more likely to require urgent admission. Since urgent repairs tend to have poorer outcomes, patients in these high-risk groups should talk to their surgeon about elective repairs. We also continue to work on systematic approaches to reducing these disparities, such as our NO HERNIA Trial.

Another focus for our hernia team is developing less expensive ways to safely repair hernias. Cutis grafts are both autologous and biologic, yielding the benefits of biologic mesh without the expense. In our new publication, we showed that the hernia recurrence rate was 3.2% at 10.5 months, which is on par or slightly better than traditional mesh. And by adding this new, third option for hernia repairs, our surgeons reduced their mesh utilization costs by 61%. Safe and less expensive, cutis grafts represent a new option for the nearly 1 million hernia repairs performed each year in the US.

Advances in Breast Reconstruction

LSU Plastic Surgery is one of the highest volume breast reconstruction providers in the country. DIEP flaps were popularized by our past chair, Dr. Bob Allen. We continue that tradition with multiple projects keep us on the cutting edge of breast reconstruction. In recent years, our faculty developed:

• The stacked lateral thigh perforator flap (LTP) as a novel option for autologous breast reconstruction

• The fleur-de-PAP flap for autologous breast reconstruction

• The stacked hemiabdominal extended perforator flap for autologous breast reconstruction
  
  

Our leadership in breast reconstruction is recognized, as exemplified by our role since 2018 as a leading enrollment site for:

• A prospective, randomized multicenter clinical study comparing outcomes in patients undergoing prosthetic acellular dermal matrix-assisted immediate post-mastectomy breast reconstruction

• A multicenter, prospective, randomized, subject and evaluator blinded comparative study of single and dual tissue flap neurotization in autologous breast reconstruction

We additionally evaluate the latest technologies in post-operative flap monitoring.

Diseases of White Adipose Tissue

Based on the technology underlying BC-MPS, human subcutaneous white adipose tissue (WAT) can be kept alive ex vivo. This has allowed Dr. Lau’s research team to study the influences of environmental obesogens such as bisphenol A (BPA) on adipocyte hypertrophy and hyperplasia.

In a funded collaboration with the Pennington Biomedical Research Center, Dr. Lau’s research team has also studied the role of SIAH2 (a ubiquitin ligase) on liposarcoma proliferation. Their results were presented at the 2019 Cell Symposia: Hallmarks of Cancer in Seattle, WA