"Many skin injuries end in scars, and in some people, it can lead to long-term cosmetic and even functional issues," said senior author Thomas Leung, MD, PhD, an associate professor of Dermatology at Penn. "Our findings suggest that rosemary extract, and specifically the antioxidant, carnosic acid, can shift the healing process from scarring to healthy skin regeneration. We don't have proven ways to consistently do that in humans."

A Viral Trend That Sparked a Scientific Question

Penn undergraduate student Jiayi Pang (left) and Penn PhD candidate Emmanuel Rapp Reyes (right) found that rosemary can help skin wounds heal without causing scars.

The idea for the project began on TikTok and Instagram. After noticing that many creators were promoting rosemary serums and rosemary-based products for better skin recovery, Pang and Rapp Reyes approached Leung to understand whether these claims had scientific merit. Their curiosity led them to begin a series of laboratory experiments.

"We hypothesized there was likely something real behind the hype because rosemary contains many antioxidants," said Pang, co-lead author of the study. "But we knew in order to really uncover its potential, we needed to prove its healing properties and uncover how exactly it was facilitating healing."

Testing Rosemary's Key Compound in the Lab

Working with mice, the research team created a cream made with carnosic acid, a naturally occurring antioxidant found primarily in rosemary. The cream sped up wound closure and helped regenerate structures such as hair follicles, oil glands, and cartilage. The scientists also found that the compound activated a skin nerve sensor known as TRPA1, which had previously been linked to the ability to heal without scars. When the cream was used on mice that lacked TRPA1, the treatment no longer produced the same regenerative effects.

"We also identified other herbs, such as thyme and oregano, that may activate TRPA1. But rosemary stood out for its potency and safety," said Rapp Reyes, co-lead author of the study. "Other natural ingredients, such as mustard oil, or the topical medication imiquimod are known to also stimulate the TRPA1 receptor, but unlike rosemary, those can cause irritation and inflammation."

Why Rosemary Works Only Where It Is Applied

The researchers discovered that rosemary's regenerative effect occurs only at the location where the carnosic acid cream is used. Applying the cream to areas of skin far from the injury did not lead to scar-free healing, emphasizing that its benefits are strictly local.

Potential for Future Wound Care Research

The Penn team advises people to speak with their healthcare providers before adding rosemary products to their skincare routine or creating homemade mixtures. Still, because rosemary is widely available and inexpensive, the researchers hope their findings encourage more exploration of its potential benefits in human wound care, especially for individuals prone to significant scarring.

"If rosemary is part of your skincare regimen and you think it's working, it likely is," said Leung. "I'm proud that the young scientists that led this research sought answers to questions in their everyday lives."

The World Health Organization reports that thousands of individuals die each year while waiting for donor organs, largely due to shortages of human tissue. In China, hundreds of thousands develop liver failure annually, yet only about 6,000 liver transplants were carried out in 2022. The success of this experimental effort suggests a possible future path for addressing the severe imbalance between organ supply and demand.

Details of the First-in-Human Pig Liver Graft

The patient was a 71-year-old man with hepatitis B-related cirrhosis and hepatocellular carcinoma who did not qualify for surgical removal of his tumors or for a human liver transplant. Surgeons implanted an auxiliary liver graft derived from a genetically modified Diannan miniature pig featuring 10 targeted gene alterations. These included the removal of xenoantigens and the addition of human transgenes designed to improve compatibility with the human immune and coagulation systems.

During the first month after transplantation, the pig liver graft performed well, producing bile and generating coagulation factors without signs of hyperacute or acute rejection. On day 38, however, physicians removed the graft after the patient developed xenotransplantation-associated thrombotic microangiopathy (xTMA), a complication linked to complement activation and injury to blood vessel linings. Treatment with the complement inhibitor eculizumab and plasma exchange resolved the xTMA. The patient later experienced several episodes of upper gastrointestinal bleeding and died on day 171.

Expert Perspectives on the Significance and Challenges

"This case proves that a genetically engineered pig liver can function in a human for an extended period," said lead investigator Beicheng Sun, MD, PhD, Department of Hepatobiliary Surgery, and President of the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. "It is a pivotal step forward, demonstrating both the promise and the remaining hurdles, particularly regarding coagulation dysregulation and immune complications, that must be overcome."

"This report is a landmark in hepatology," noted Heiner Wedemeyer, MD, Co-Editor, Journal of Hepatology, and Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany, in an accompanying editorial. "It shows that a genetically modified porcine liver can engraft and deliver key hepatic functions in a human recipient. At the same time, it highlights the biological and ethical challenges that remain before such approaches can be translated into wider clinical use. Xenotransplantation may open completely new paths for patients with acute liver failure, acute-on-chronic liver failure, and hepatocellular carcinoma. A new era of transplant hepatology has started."

"The publication of this case reaffirms the Journal of Hepatology as the world's leading liver journal. We are committed to presenting cutting-edge translational discoveries that redefine what is possible in hepatology," added Vlad Ratziu, MD, PhD, Editor in Chief, Journal of Hepatology, and Institute for Cardiometabolism and Nutrition, Sorbonne Université and Hospital Pitié Salpêtrière, Paris, France.

Nail infections are typically caused by fungi, though bacteria can occasionally be involved. These conditions are widespread, affecting an estimated 4-10% of people worldwide, with rates climbing to nearly 50% among adults aged 70 and older.

These infections can create serious complications in vulnerable groups such as older adults and individuals with diabetes. Despite their prevalence, they remain difficult to eliminate.

Why Current Treatments Often Fall Short

Standard therapies include oral antifungal medications taken as pills and topical products placed on the surface of the nail. Oral medications usually take 2-4 months to show results and are generally effective, but they also pose risks for side effects, particularly in patients with other health conditions.

Topical treatments are considered safer, but they often require very long application periods, sometimes lasting years. Even then, they frequently fail to fully clear the infection or the infection returns.

One major obstacle is that most medications struggle to pass through the dense structure of the nail, preventing them from reaching the fungi or bacteria living beneath it. Even the best topical antifungal options achieve relatively low cure rates, underscoring the need for treatments that can reliably reach microbes deep within the nail.

Hydrogen Sulfide Shows Strong Antimicrobial Potential

A research team from the University of Bath and KCL has identified hydrogen sulfide (H2S) as a promising alternative. This small, naturally occurring gas appears capable of penetrating the nail plate far more effectively than existing topical drugs.

Earlier studies already suggested that H2S travels through nail tissue with ease. The new findings show that it also has powerful antimicrobial activity, killing a broad spectrum of pathogens, including fungal species that do not respond well to common antifungal medications.

In controlled laboratory experiments, the researchers used a compound that releases hydrogen sulfide as it breaks down. They found that the gas disrupts microbial energy production and causes irreversible damage to the cells, ultimately destroying the fungi responsible for infection.

The study is detailed in Scientific Reports.

Researchers See Promise for a Future Topical Therapy

Dr. Albert Bolhuis of the University of Bath's Department of Life Sciences said: "Thanks to its ability to efficiently reach the site of infection and its novel mode of action, we believe that a topically applied medicine containing hydrogen sulfide could become a highly effective new treatment for nail infections, which avoids the limitations of current therapies.

"Our research lays the foundation for a compelling alternative to existing treatments, with the potential to improve outcomes for patients suffering from persistent and drug-resistant fungal nail infections."

Hydrogen sulfide does have a strong smell and some level of toxicity. However, researchers emphasize that the concentrations needed for treatment appear to be far below harmful levels, and the right formulation should greatly reduce any unpleasant odor.

Next Steps Toward Patient Use

So far, the research has been conducted only in vitro. Even so, the team hopes to continue development and create a topical treatment suitable for patients within the next five years.

Professor Stuart Jones, Director of the Centre for Pharmaceutical Medicine Research at KCL, said: "We are looking forward to translating these findings into an innovative topical product that can treat nail infection."