Laboratory for Fetal and Regenerative Biology
Advancing regenerative and translational therapies to prevent injury, restore healing, and regenerate tissues.
Lab Overview
The Laboratory for Fetal and Regenerative Biology (LFRB), co-led by Dr. Kenneth W. Liechty and Dr. Carlos Zgheib, is dedicated to advancing translational regenerative medicine at the intersection of surgery, inflammation, and tissue repair. Our mission is to develop mechanism-driven therapies that prevent tissue injury, restore normal healing, and regenerate damaged organs across a range of surgical and medical conditions.
Our research integrates nanomedicine, biomaterials, small-molecule therapeutics, and stem cell biology to address critical unmet clinical needs in wound healing, inflammatory disease, and organ injury. With a strong emphasis on clinically relevant models and clear translational endpoints, we aim to move discoveries from bench to bedside and improve outcomes for patients.
Principal InvestigatorsKenneth W Liechty, MD, FACS, FAAP Professor, Pediatrics |
Professor of Surgery Professor of Biomedical Engineering Professor of Pharmacology Member of the Graduate Faculty
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Projects
Impact: A single nanotherapeutic platform targeting multiple high-impact diseases.
CNP-miR146a is a cerium oxide nanoparticle–microRNA therapeutic designed to modulate inflammatory and oxidative stress pathways. Our translational work spans diabetic wound healing, acute lung injury (ALI), and inflammatory bowel disease (IBD), employing topical, intratracheal, and enteric delivery strategies. We investigate macrophage modulation, endothelial function, and tissue repair mechanisms to prevent and reverse injury, advancing CNP-miR146a toward clinical development with clear therapeutic endpoints.
Impact: Developing scalable small-molecule therapeutics to restore chronic wound healing.
This project focuses on small-molecule CXCR4 agonists to enhance progenitor cell recruitment, angiogenesis, and tissue remodeling in diabetic ulcers. Using preclinical wound models and mechanistic studies, we define translational strategies for non-biologic therapeutics with rapid clinical applicability.
Impact: A preventive biomaterial that protects high-risk skin from injury.
Nanosilk is a biomimetic topical device engineered to preserve skin integrity and collagen structure under mechanical stress. Preclinical studies demonstrate its ability to reduce inflammation and prevent pressure injuries, with a focus on high-risk populations such as patients with diabetes or limited mobility. The work bridges materials science with clinically relevant endpoints for tissue protection.
Impact: Advancing therapies to prevent and repair uterine scarring for improved reproductive health.
This project investigates mechanisms of uterine scarring and impaired tissue regeneration following injury or surgery. Using in vivo models, we examine progenitor cell recruitment, extracellular matrix remodeling, and targeted molecular interventions to restore uterine structure and function. The goal is to develop translational therapies that preserve fertility and enhance reproductive outcomes.
Impact: Combining stem cells and microRNA insights to restore skin resilience.
We study mesenchymal stem cells, SCF-mediated progenitor cell migration, and microRNA pathways (including miR-29a) to correct the biomechanical deficits of diabetic skin. This NIH-style investigation defines mechanistic targets to improve extracellular matrix organization, tissue strength, and regenerative potential, guiding translational strategies for chronic wound repair.
Impact: Unlocking fetal regenerative programs to enhance adult tissue repair.
Focusing on myocardial infarction, skin injury, and tendon damage, we examine the regenerative capacity of fetal tissues and developmental signaling pathways. Insights inform translational approaches to reactivate pro-repair programs in adult tissues, with applications in surgical regeneration and repair strategies.
LFRB Projects
CNP-miR146a, a Novel Treatment that Corrects Impaired Diabetic Wound Healing
We have designed a novel cerium oxide nanoparticles (CNPs) that possess ROS scavenging properties and have conjugated them with a miR-146a mimetic, to target both oxidative stress/ROS and pro-inflammatory signaling. Our studies have shown that local treatment of the diabetic wound with CNP-miR146a conjugate resulted in reduced time to wound healing with increased strength and elasticity in a murine model. This was further validated in a porcine model where treatment with CNP-miR146a resulted in reduced time to wound healing.
Intratracheal delivery of CNP-miR146a prevents and rescues Acute Lung Injury rescues lung function following Acute Lung Injury (ALI)
ALI in its most severe form, ARDS, is to date the most life-threatening complication reported from COVID-19. Early data suggest that more than 40% of individuals hospitalized for severe and critical COVID-19 developed ARDS and over 50% of those diagnosed died from the disease. While the etiology of ALI is multifactorial, a central pathogenic feature of the progression to ARDS is a persistent activation of inflammation and oxidative stress. In a bleomycin-induced model of ALI, we found that one-time administration of CNP-miR146a prevents inflammation and fibrosis, and improves pulmonary mechanics.