Professor of Chemical and Biomolecular Engineering
Professor of Biomedical Engineering
Professor of Pathology, Microbiology and Immunology
My current research is in the design, synthesis, and characterization of polymeric biomaterials for bone tissue engineering. Although autologous bone graft (vital tissue transplanted from one site in the patient to another) has the best capacity to stimulate healing of tissue defects, explantation both introduces additional surgery pain and also risks donor-site morbidity. One promising alternative to autograft is synthetic biomaterials that are designed to enhance healing through the natural tissue remodeling process. Polyurethanes comprise a class of synthetic polymers that are of fundamental interest to us because their mechanical and biological properties can be tuned to targeted values by controlling the structure. New materials having targeted biological and mechanical properties are being developed for three orthopaedic clinical indications:
Injectable polyurethane scaffolds for drug and gene delivery. Due to the increasing recognition of the need for healing therapeutics administered by minimally invasive surgical techniques, synthesis of injectable scaffolds for tissue repair is an important area of biomaterials research. Polyurethanes can be injected as a two-component reactive liquid mixture that cures in situ. Orthopaedic clinical indications for injectable therapeutics include distal radius fractures and treatment for problematic fracture healing. We have synthesized high porosity (>95%) two-component polyurethane foam scaffolds that support the attachment and proliferation of osteoprogenitor cellsin vitro and degrade at a controlled rate. We are applying this technology to develop biologically active injectable therapeutics that deliver growth factors and plasmids to enhance bone wound healing.
Polyurethane scaffolds for ex vivo bone and ligament tissue engineering. We are collaborating with researchers at Virginia Tech to prepare engineered bone tissue ex vivo in a perfusion bioreactor by culturing bone marrow stromal cells in biodegradable segmented polyurethane scaffolds. We aim to direct osteoblastic maturation and synthesis of bioactive factors by controlling the mechanical properties of the scaffolds and using novel perfusion strategies. We envision using these materials as implants to stimulate bone healing in vivo.
Biodegradable bone/polyurethane composite fracture fixation devices. Traditionally, bone fractures are treated by fracture reduction and subsequent fixation. There is a compelling clinical need for a resorbable biomaterial that has the appropriate biomechanical and biological properties for fracture reduction and fixation, eliminates the need for removal surgery, and integrates with host bone. We are collaborating with a leading allograft bone company to prepare resorbable allograft bone/polyurethane composite fracture fixation devices, such as plates, screws, and intramedullary rods, by reactive liquid molding processes.
Eastman Chemical Company, 1992 - 1994
Bayer Corporation, Polyurethanes Division, 1999 - 2002
(for a full listing, click here and follow the research link)
AE Hafeman, KJ Zienkiewicz, E Carney, B Litzner, CW Stratton, JC Wenke, and SA Guelcher. Local delivery of tobramycin from injectable biodegradable polyurethane scaffolds. J Biomat Sci Polym Ed 21, 95-112, 2010.
JE Dumas, T Davis, GE Holt, T Yoshii, DS Perrien, JS Nyman, TM Boyce, SA Guelcher. Synthesis, Characterization, and Remodeling of Weight-bearing Allograft Bone/Polyurethane Composites in the Rabbit. Acta Biomaterialia 6, 2394 – 2406, 2010.
B Li, K Brown, JC Wenke, SA Guelcher. Sustained release of vancomycin from polyurethane scaffolds inhibits infection of bone wounds in a rat femoral segmental defect model. Journal of Controlled Release 145, 221 – 230, 2010.
T Yoshii, AE Hafeman, JS Nyman, JM Esparza, K Shinomiya, DM Spengler, GR Mundy, GE Gutierrez, SA Guelcher. A Sustained Release of Lovastatin from Biodegradable, Elastomeric Polyurethane Scaffolds for Enhanced Bone Regeneration. Tissue Engineering Part A 16(7):2369-79, 2010.
JE Dumas, K Zienkiewicz, SA Tanner, EM Prieto, S Bhattacharyya, SA Guelcher. Synthesis and Characterization of an Injectable Allograft Bone/Polymer Composite Bone Void Filler with Tunable Mechanical Properties. Tissue Engineering Part A 16(8):2505-18, 2010. 25. NS Ruppender, JA Sterling, JS Nyman, GR Mundy, SA Guelcher. Substrate rigidity modulates osteolytic potential of metastatic breast cancer cells. PLoS One 5(11):e15451, 2010.
AE Hafeman, KJ Zienkiewicz, JM Davidson, SA Guelcher. Characterization of Degradation Mechanisms of Biodegradable Lysine-derived Aliphatic Polyurethanes. Biomaterials 32(2):419-29, 2011.