David Dean, Ph.D.

Tethered Ligands for Craniofacial Bone Tissue Engineering

David Dean, Ph.D. is an Associate Professor of Materials Science and Engineering and Plastic and Reconstructive Surgery at The Ohio State University in Columbus, Ohio. He directs the Osteo Engineering Laboratory which focuses on developing regenerative medicine therapies for use in musculoskeletal reconstructive surgery. He earned the PhD degree at the City University of New York (New York, NY) in 1993. His research on craniofacial regenerative medicine currently emphasizes: bone tissue engineering using bone progenitor cells, relevant growth factors, bioreactor technologies, resorbable materials, and computer aided design and biomechanical analysis of 3D printed scaffolds.

Tethered Ligands for Craniofacial Bone Tissue Engineering
Abstract

Autologous bone transplantation is the gold standard for patients suffering critical size or large bone deficits due to congenital defect or secondary to senescence, cancer resection, trauma, bone infection, or reconstructive surgery. Many of these patients have insufficient or inadequate sources of bone for grafting. Other than products for small defects, there are currently no commercially available inert or tissue engineered artificial bone substitutes. The first problem is a lack of resorbable materials, that predictably and reliably degrade in time frames relevant to bone healing, and that can be formed (e.g., 3D printed) in patient-specific configurations. A second limitation is an inability to control the release, and prevent systemic circulation of, powerful cytokines such as BMP-2, a phenomena associated with inflammation and increased neoplasm risk. We have solved the first problem by inventing a new “ring opening” method for synthesizing poly(propylene fumarate) (PPF). ROP synthesis provides PPF with little molecular mass dispersity thus insuring reliable resorption kinetics and highly accurate 3D printing. We propose to solve the second problem with a novel functionalization strategy, the tethering of bioactive ligands (short peptides) to the surface of 3D printed PPF scaffolds. This strategy will allow accurate dosing and avoid the release of whole, systemically-circulating cytokines. The proposed project seeks to validate an in vitro optimized dose of RGD, bFGF, BMP-2, and OGP ligands for the¬†effective use of our PPF scaffolds in a critical size mandibular defect model in the rabbit. The cell-free technology resulting from the proposed project would justify a follow-on large animal model study that itself would validate a follow-on clinical trial. Our strategy would be a paradigmatic shift in scaffold functionalization, from drug release to tethered ligands, providing the first bone substitute for the regeneration of critical size or larger defects.

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