Biography

Research Interests

1. Ex Vivo Produced Oral Mucosal Grafts: (Collaborators: Cynthia Marcelo, Blake Roessler, Ania Bielinski)

Our long-term goal is to produce a “smart” oral mucosal graft, ex vivo, that will be used for reconstruction of major oral defects that are seen secondary to oncologic resection, traumatic events or developmental disturbances.    At present, oral mucosa is in limited supply for use in major reconstructive procedures.    Other alternatives such as skin introduce disadvantages, such as, the presence of adnexal structures and a different pattern of keratinization that can lead to a compromise in oral function.

                    This proposal plans to harvest human oral keratinocytes from keratinized mucosa, expand them in vitro, and seed them onto an acellular, non-immunogenic dermal equivalent, AlloDerm®, to produce a mucosal equivalent with similar anatomic and handling properties as native oral mucosa.  The ex vivo produced oral mucosal composite (EVPOMC) will be developed in an environment free of serum and transformed irradiated feeder cells, in a defined medium, so that it can be used for grafting back into autogenous human recipients. This has, in fact, been accomplished, and we anticipate going into phase I clinical trials using "normal" EVPOMC grafts in the near future.  

                    The oral keratinocytes of the EVPOMC, in a funded 5 year R01 from the National Institute of Health (NIH) grant, will be transfected with a plasmid, using a novel approach to alter cell membrane viscosity, to cause them to oversecrete vascular endothelial growth factor (VEGF), thus making this a “smart” oral mucosal grafting device.  We will evaluate vascular ingrowth into the EVPOMC, by histology and immunohistochemistry, to assess the functionality of the inserted plasmid in the device.    The safety and efficacy of the device, which is necessary for US Government FDA approval, will be tested in SCID mice and minipigs. 

                    The successful transfection and grafting of our oral mucosal device, in the NIH proposed investigation, will allow us to gather the necessary preclinical data, to use for submission to regulatory agencies, for the translation of this technology into an expanded Phase I human clinical trial.

2. Fabrication of Scaffolds for Bone Tissue Engineering (Collaborators: Scott Hollister, Paul Krebsbach, Juan Taboas, TM Gabe Chu, John Halloran, Rachel Maddox)

Our interdisciplinary bioengineering partnership plans to develop an image based approach for designing and manufacturing patient site-specific biomaterial scaffolds with specific internal architecture using an image based engineering design method combined with a solid free form fabrication manufacturing approach.   In this proposal we will combine the efforts of our multidisciplinary team to focus on the development of a functional prosthesis to reconstruct the temporomandibular joint (TMJ), since at present, there is no US Government FDA approved device for this anatomic region.

We hypothesize that “the fabrication of a designed and manufactured biomaterial scaffold, containing chondrocytes and bone marrow stromal cells, in different locations on the same scaffold, can successfully reconstruct a TMJ by forming a fibrocartilaginous cap or joint surface on top of a bony strut.   This scaffold, composite of cartilage and bone, similar in structure to a costochondral rib graft (a bony rib with a cartilaginous cap), can be fixated and eventually integrated into the underling bony vertical ramus of the mandible.”  This hypothesis, which depends on the generation of multiple tissues on the same construct, through cell-material interactions on specifically designed anatomic 3D scaffolds, presents many complex engineering and biological challenges. 

            Tissue engineering studies have shown that mean pore size, scaffold material, specific cells and mechanical stimulus individually can influence whether bone or cartilage is generated.  However, no comprehensive studies have been performed that specifically study the interaction of all these factors, especially with designs of controlled scaffold pore geometry and shape.  Since controlling both bone and fibrocartilage generation is critical for engineering TMJ replacements, as well as other skeletal reconstructions, we must understand the interactions of these factors to optimize bone and fibrocartilage production.  We recently had funded a 4 year NIH grant (Scaffold Architecture) and a 5 year NIH Bioengineering Research Partnership (BRP) grant (Joint Reconstruction) to pursue this line of research. The PI on both proposals is Scott Hollister.

Selected Publications

Chu TMG, Orton DG, Hollister SJ, Feinber SE, Halloran JW: Mechanical and in vivo performance of hydroxyapatite implants containing controlled internal architecture, Biomaterials (accepted)

Izumi K and Feinberg SE: "Skin and Mucosal Substitutes" in "Biomaterials", Oral Maxillofacial Clinics of North America
(accepted)

Feinberg SE, Hollister SJ, Halloran JW, Chu TMG, Krebsbach PH: Image-Based Biomimetic Approach to Reconstruction of The Temporomandibular, Joint. Cells, Tissues, Organs 169:3:309-321, 2001

Izumi K, Terashi H, Marcelo C L, Feinberg, SE: Development and Characterization of A Tissue Engineered Human Oral Mucosa Equivalent Produced In A Serum-free Culture System. J Dent Res 79(3):798-805, 2000

Izumi K, Feinberg, SE, Teraski H, Marcelo CL: "Evaluation of Transplanted Tissue-engineered Oral Mucosa Equivalents to SCID Mice", Tissue Engineering (submitted Tissue Engineering)

Yoshizawa M, K, Feinberg, SE, Marcelo CL, Elner, VM: "Development of An Ex Vivo Produced Full Thickness Conjunctival Graft", Current Eye Reserach (submitted: Current Eye Research)