Puhan He, DMD, MD
Application of UBM laden with GMSC-EVs in fibrin hydrogel in Rat Tongue Myomucosal Regeneration
Dr. Puhan He is a PGY-2 resident in Oral and Maxillofacial Surgery Department at the Hospital of the University of Pennsylvania. She earned her DMD from Harvard School of Dental Medicine. There, she studied and authored multiple publications on anatomical variations in the head and neck region, to better delineate best practices in pre-operative planning. Her current clinical and research interests include reconstructive craniomaxillofacial surgery, regenerative medicine and global surgery. Dr. He plans to continue research geared towards improving clinical outcomes and patient care.
Reconstruction of large craniofacial tissue defects, particularly, reconstruction of the tongue defects following ablative surgery of oral cancer, remains one of the major challenges in oral and maxillofacial surgery. Even though much progress has been made in reconstructive principles and techniques, fully functional recovery of the tongue defects is still a great challenge. Currently, microvascular soft tissue free flaps, made up of skin, subcutaneous adipose tissue and fascia, are the gold standard for tongue reconstruction. However, these free flaps do not allow for both structural and functional restoration of the tongue, e.g. restoration of its muscular-like tissues and critical vocal, chewing, swallowing, and tasting functions. Meanwhile, harvesting these flaps will always result in donor site morbidity that will cause some degrees of local pain, edema, limb weakness, and scar formation. In recent years, efforts have been made to explore the use of mesenchymal stem cells (MSCs) and their derivative cell-free products, e.g. extracellular vesicles (EVs), in combination with biomaterials to generate tissue engineering and regenerative (TE/RM) products to facilitate repair/regeneration of damaged tissues. Most recently, we have shown that combined use of EVs released by gingiva-derived MSCs (GMSC-EVs) and porcine small intestine submucosa extracellular matrix (SIS-ECM) could facilitate myomucosal regeneration in tongue defects of rats. This work will test the hypothesis that urinary bladder matrix (UBM) laden with GMSC-EVs encapsulated in fibrin hydrogel as a delivery system to ensure a sustained release of EVs represents a promising approach to promote myomucosal regeneration of the tongue. Specifically, we will generate UBM constructs laden with GMSC-EVs and evaluate their therapeutic effect on myomucosal regeneration in a critical-sized tongue defect model in rats and the potential mechanisms, shedding light on utility in clinical settings.