Symposium on Molecular, Cellular and Tissue Engineering
The Molecular, Cellular and Tissue Engineering Symposium will be held on Friday, 8 February 2008. It will will feature a Special Keynote Session entitled Accomplishments and Perspectives. Keynote Addresses will be given by two prominent scientist and engineers Rena Bizios, Ph.D, UT at San Antonio and Elizabeth Cosgriff-Hernandez, Ph.D., Texas A&M University, College Station.
Challenges and Opportunities in Tissue Engineering, Genetic Engineering and Regenerative Medicine
Keynote Address: Rena Bizios Ph.D., Biomedical Engineering Department, The University of Texas at San Antonio
Recent trends in medicine and new approaches in health-care practice necessitate expansion of the scope of biomedical engineering into new directions, which include (but are not limited to) regenerative capabilities of functional tissues within biomaterial scaffolds, novel material formulations and structures, use of pluripotent stem cells, and changing concepts of biocompatibility. Developments in tissue and genetic engineering, which are pertinent to regenerative medicine, provide challenges and, at the same time, great opportunities for biomedical engineers. These areas are becoming a substantive part of the present cutting-edge milieu and, undoubtedly, will be a major component of the future endeavors in bioengineering.
Rena Bizios is a Peter T. Flawn Professor in the Department of Biomedical Engineering at the University of Texas at San Antonio (UTSA), San Antonio, TX. She earned her B.S. (Cum Laude) degree in Chemical Engineering from the University of Massachusetts, M.S. degree in Chemical Engineering from the California Institute of Technology, and Ph.D. degree in Biomedical Engineering from the Massachusetts Institute of Technology.
Dr. Bizios received the Outstanding Alumna in Engineering Award of the Society of Women Engineers, College of Engineering, University of Massachusetts, Amherst, MA (1985), the Rensselaer Alumni Association Teaching Award, Rensselaer Polytechnic Institute (1997), and the Clemson Award for Contributions to the Scientific Literature of Biomaterials from the Society for Biomaterials (1998). She was Jubileums Professor at Chalmers University of Technology, Göteborg, Sweden (fall of 2002), Chercheur Associé (spring of 2003) and Directeur de Recherche Associé, Centre National de la Recherche Scientifique, Faculté de Médicine Saint-Louis Lariboisiére, Université Paris VII, Paris, France (fall of 2005). She is Fellow of the American Institute for Medical and Biological Engineering (AIMBE), International Fellow of Biomaterials Science and Engineering of the International Union of Societies for Biomaterials Sciences and Engineering, and Fellow of the Society of Biomedical Engineering (BMES).
Dr. Bizios has been an active participant (and held some elected member/officer positions) in the Society for Biomaterials, the Biomedical Engineering Society, and the American Institute of Chemical Engineers. She is a member of the editorial board of the Journal of Biomedical Materials Research. She has participated in various (and chaired some) NIH Study Sections, NSF Review Panels, and similar national-level review committees. She is co-author of An Introduction to Tissue-Biomaterial Interactions, a textbook for undergraduate and for first-year, graduate biomedical engineering students. Her research interests include cellular engineering, tissue regeneration, biomaterials (including nanostructured ones), bone tissue engineering and biocompatibility.
Biodegradable Polyurethanes in Regenerative Medicine
Keynote Address: Elizabeth Cosgriff-Hernandez, Ph.D., Department of Biomedical Engineering, TAMU College Station
After over 40 years of use in biomedical applications, polyurethanes remain a popular choice due to their exceptional biocompatibility, mechanical properties and versatility. The mechanistic understanding gained in the pursuit of enhanced polyurethane biostability was recently applied to the development of a new class of biodegradable materials. The potential of these systems in regenerative medicine will be presented with special emphasis on orthopaedic applications.
Motivation: One of the greatest challenges in biomaterial design is decoupling the effect of different scaffold properties on biological responses. A number of structure-property relationships have overlapping components. For example, it is well established that percent crystallinity can be used to predict polymer modulus. Highly crystalline polyesters have also been shown to have a slower rate of hydrolysis as compared to their amorphous counterparts. The dual impact of both mechanical properties and degradation rate on tissue regeneration can make interpreting results and identifying key relationships difficult. A polymer system with several mechanisms for modulating properties would provide the tools necessary to isolate effects. Segmental modifications of polyurethanes can be used to generate a library of polymers with broad structural diversity and derived properties. The versatility of the polyurethane design provides the spectrum of polymer properties necessary to probe specific tissue-biomaterial interactions.
Polyurethane Chemistry: Polyurethanes are a class of polymers that contain the urethane (-NH-CO-O-) linkage that is typically generated through the addition of an isocyanate to a hydroxy group. Segmented polyurethanes most often used in biomedical applications are block copolymers consisting of relatively high molecular weight polyol soft segments linked together by urethane containing hard segments. Polyurethane chemistry dictates the chemical, physical and biological properties of the resulting material and can be exploited to prepare a variety of materials including segmented elastomers, rigid thermosets, adhesives, and foams. Optimal design of biodegradable polyurethane scaffolds should meet the following criteria: 1) biocompatibility and clearance of all degradation products with minimal inflammation, 2) independent control of biodegradation and mechanical properties, 3) system-responsive degradation.
Biodegradable Hard Segments: Development of biodegradable polyurethanes requires a change from diisocyanates historically used in biostable formulations. Aromatic diisocyanates were often chosen for biomedical applications such as pacemaker lead coverings due to their enhanced mechanical properties. However, concerns that the degradation of these aromatic diisocyanates (i.e. 4,4'-methylenediphenyl diisocyanate (MDI)) could generate potentially carcinogenic compounds (i.e. 4,4'-methylenedianiline (MDA)) has limited their translation to biodegradable polymers. Therefore, these aromatic diisocyanates were replaced with aliphatic diisocyanates such as lysine-diisocyanate (LDI), hydrogenated MDI (H12MDI) and hexamethylene diisocyanate (HDI) that are more likely to have non-toxic degradation products. In addition to biocompatible diisocyanates, Skarja et al. incorporated enzyme sensitive linkages into the hard segments by synthesizing peptide-based chain extenders.
Biodegradable Soft Segments: Tailoring the soft segment to achieve controlled degradation is a more common design strategy. To this end, a number of polyurethanes have been synthesized with biodegradable soft segments including poly(lactic acid), poly(glycolic acid) and poly(ε-caprolactone) (PCL). Initial studies selected candidate polyesters based on their established hydrolytic degradation in vitro and in vivo. Polyurethane degradation and mechanical properties were correlated with the soft segment content and molecular weight. It has also been proposed that guided biodegradation of the scaffold can be achieved by incorporating the collagen oligopeptide sequences in the soft segment.
Summary: Biodegradable polyurethanes have been shown to support the ingrowth of cells and undergo controlled degradation to non-cytotoxic decomposition. This combined with the tunable biological, mechanical, and physicochemical properties make these new materials excellent candidates for tissue engineering scaffolds. This presentation will summarize the recent advances in the synthesis of these biodegradable polyurethanes and the application in scaffolds for regenerative medicine.
Dr. Cosgriff-Hernandez is an Assistant Professor in the Department of Biomedical Engineering at Texas A&M University in College Station, Texas. She received a B.S. in Biomedical Engineering and a Ph.D. in Macromolecular Science and Engineering from Case Western Reserve University in Cleveland, Ohio. Her graduate research, under the guidance of Professors Anne Hiltner and James Anderson, elucidated key cell-material interactions and biodegradation mechanisms of biomedical polyurethane elastomers. She continued her research training with a postdoctoral fellowship in orthopaedic tissue engineering under the direction of Professor Antonios Mikos at Rice University in Houston, Texas. Dr. Cosgriff-Hernandez was the recipient of the 2005 Society for Biomaterials Student Award for Outstanding Research and the UT-TORCH Postdoctoral Fellowship.
Research in the Cosgriff-Hernandez Lab is focused on biomaterial synthesis, structure-property relationships, cell-material interactions, musculoskeletal tissue engineering and biodegradation characterization. Specifically, novel block copolymer systems are under investigation as polymeric scaffolds for tendon and ligament tissue engineering. Complimentary experiments that generate quantitative models of tissue remodeling will be used to improve the design of new biomaterials and guide tissue regeneration strategies.
Current projects include:
- Synthesis of Novel Block Copolymers
- Biodegradation/Tissue Regeneration Continuum
- Mechanical Stimulation of Tissue Engineering Constructs
- Impact of Inflammation on Tissue Regeneration
