Grants We Funded

Abstract
Currently, the greatest impediment to engineering complex, 3D tissues arises from the inability to fabricate or encourage in situ development of an adequate vascular network. While contemporary tissue-engineered dermal substitutes can succeed when applied to well-vascularized wound beds, their insufficient vascular invasion leads to unsuccessful integration and high failure rates in poorly vascularized wound beds. Unfortunately, the prevalence of poorly vascularized wounds, such as those that have previously been irradiated or those with exposed hardware, bone or tendon, highlights the need for an engineered dermal replacement with improved angiogenic capacity. In order to address this critical need, we propose fabrication of a biocompatible and biodegradable tissue-engineered dermal replacement scaffold with novel micro-architectural properties and cell signaling moieties that will promote efficient, guided invasion of endothelial cells, resulting in the creation of a vascular network capable of supporting the metabolic needs of the scaffold, thereby increasing the rate of successful graft incorporation. The catalyst of this efficient neovascularization lies in the scaffold's pioneering arrangement of regularly spaced differential collagen densities, generated by the orderly encapsulation of collagen microspheres of a particular density in bulk collagen of a differing density. Preliminary work demonstrated that cells preferentially and robustly invade scaffolds at the interfaces of differential densities. For the proposed study, collagen microspheres of a particular density of type I collagen will be fabricated using an oil emulsion technique and subsequently doped with growth factors. Novel, custom-made 7 mm diameter microsphere scaffolds (MSS) will be fabricated by embedding closely packed, doped-up microspheres in type I collagen bulk of a differing density. Microsphere scaffolds will be implanted subcutaneously in dorsa of WT C57bl/6 mice. Following 7 or 14 days of implantation, scaffolds will be procured and subsequently analyzed for cellular and vascular invasion. By altering the mechanical and spatial cues within hydrogel scaffolds we have developed a novel tissue engineered matrix with regularly spaced differential collagen densities that significantly improves cellular and vascular invasion. We believe our novel, microsphere-containing scaffolds hold tremendous promise for creating the optimal wound scaffold and revolutionizing wound healing.

Biography
Dr. Jason Spector is a nationally recognized clinician, researcher and educator. He holds two patents, and has been an integral part several Cornell University-Weill Cornell Medical College translational research teams. He participates in the NIH and Howard Hughes Medical Institute sponsored Clinical Summer Immersion for Biomedical Engineering Program, mentoring engineering doctoral students. Since 2007, he has been a lecturer at Cornell University's Biomedical Engineering Science and Technology course, "Approaches to Problems in Human Needs." Dr. Spector serves as an Ad-Hoc reviewer for six prestigious medical journals, and has presented at national and international medical meetings. He recently served as Moderator of the Emerging Technologies Section, at the American Surgical Congress in 2011.