Grants Funded

Abstract

Impact Statement: Deficiencies in soft tissue can occur after oncologic resection or traumatic events leading to functional impairment for the patient and exorbitant medical expenditures. Reconstructive approaches are suboptimal. Our results will have a positive impact by laying the foundation in developing new and translatable reconstructive approaches for large volume soft tissue loss.

Project Summary: Advances have allowed for the in vitro creation of thin vascularized replacement grafts but lack of a continuous and anastomosable vasculature limits translation and scale-up of size. There is little knowledge about the utility of surgical approaches in facilitating prompt inosculation of implanted engineered tissues. Our long-term goal is to develop surgical strategies which augment the vascular integration of thick engineered flaps; which would offer more clinical relevance. The objective of this proposal is to define the mechanisms and impact of a coordinated surgical and additive manufacturing approach for the rapid vascularization of an engineered adipose flap, which would be applicable for soft tissue reconstruction. We have developed a novel microsurgical tactic, termed “vascular micropuncture”, which increases the angiogenic capabilities of the rat recipient vasculature in order to quickly perfuse an adjacently placed un-anastomosable thin engineered graft. This results in graft perfusion within 24 hours and a doubling of neovascularization. If combined with standard vascular interposition conduits (e.g. saphenous vein), which can be used to lengthen the recipient pedicle, it offers an easily translatable approach for thick flap engineering. Our central hypothesis is that vascular micropuncture and lengthening of the recipient vasculature can enable direct inosculation and rapid perfusion of a thick adipose flap that is intraoperatively bioprinted with adipocyte/endothelial progenitor cell spheroids. The rationale is that completion of these studies will reveal how to best optimize complementary tactics for the inosculation of concurrently engineered in situ flaps. Our central hypothesis will be tested by two specific aims: 1) Demonstrate that MP induced angiogenesis can be controlled by varying puncture intervals/density; 2) Coordinated in situ thick flap generation and surgically induced rapid perfusion. We will pursue these aims using innovative combinatorial techniques from both the surgical and engineering sciences, including recently developed microsurgical and aspiration assisted bioprinting approaches. This proposed research is significant because it will integrate these advances to intraoperatively assemble and rapidly perfuse a thick engineered flap; a noteworthy advance from the often-described thin engineered graft.

Biography
I am an attending reconstructive plastic surgeon in the Department of Surgery at the Penn State Hershey Medical Center and College of Medicine, where I direct the Plastic Surgery Research Laboratory and the Clinical Microsurgery program. I also serve as an Associate Editor for the Journal of Surgical Research (Plastic Surgery and Wound Healing). My clinical practice primarily deals with wounds that often require specialized microvascular reconstructive expertise. Thus, I have ongoing research interests in the use of adipose derived stem cells and endothelial progenitor cells to create autologous vascularized constructs for reconstructive applications. Over the past few years while acquiring an MSc (Stem Cells and Regeneration) and having NIH-K12 and AAPS Academic scholarships, I have expanded my knowledge of materials science and additive manufacturing to develop a unique surgical perspective to tissue engineering. I have become keenly aware of the limitations associated with vascular inosculation and perfusion following graft implantation, including intraoperative bioprinting. From this knowledge gap our novel surgical approach was developed, preliminary studies were executed, and this proposal was grown. For this proposal we will integrate surgical (Ravnic) and engineering (Ozbolat) tactics to optimize angiogenesis at the both the recipient site and graft itself to accelerate inosculation of a thick vascularized adipose flap.