Dr. Matthew L. Becker
Associate Dean for Research, W. Gerald Austen Professor of Polymer Science & Biomedical Engineering College of Polymer Science and Polymer Engineering, Goodyear Polymer Center
The University of Akron
Category of Humanitarian Benefit: Health and Medical
Short Biography/Background of the Nominee: Matthew Becker is the W. Gerald Austen Endowed Chair in the College of Polymer Science and Polymer Engineering at The University of Akron. Professor Becker joined UA in 2009 where he is a Professor of Polymer Science and Biomedical Engineering. To date, his group has published more than 100 papers and has 20 patents pending. He is the founder of two start-up companies, 3D BioResins & 3D BioActives. In 2015, Professor Becker was one of two scientists worldwide under 40 named Macromolecules-Biomacromolecules Young Investigators.
Professor Becker completed his PhD in organic chemistry in 2003 at Washington University in St. Louis under the direction of Professor Karen L Wooley as an NIH Chemistry-Biology Interface Training Fellow. In 2003, Dr Becker moved to the Polymers Division of the National Institute of Standards and Technology for a NRC Postdoctoral Fellowship in biophysics. He joined the permanent staff in 2005 and led projects in bioimaging and combinatorial methods for tissue engineering working with the NIH, Industry and FDA to advance measurement methods for combination products. He received his BS in chemistry in 1998 from Northwest Missouri State University.
Project Name and Description: AMINO ACID BASED POLY(ESTER UREA)S FOR REGENERATIVE MEDICINE
The development of a fundamental understanding of the role of architecture and the influence of stoicheometry and chirality on the physical and chemical properties is critical to the development of new degradable materials. There are a number of biodegradable polymers including poly(ε-caprolactone) (PCL), poly(lactic acid) (PLA), poly(glycolide) (PGA), and copolymers thereof that used commercially and while their properties in vitro and in vivo are largely understood, their range of physical and chemical properties is somewhat limited. There are number of other, albeit less well known, degradable polymers used clinically including polyurethanes (PU), poly(orthoesters), poly(carbonates), poly(ester urea) (PEU), and more recently poly(a-amino acids). An increasingly common strategy has been to use naturally occurring amino acids as building blocks for monomer precursors.
While these classes of materials have had a transformative influence on the design of next generation materials for regenerative medicine, in general, the mechanical properties have been insufficient for load bearing applications. The maximum reported mechanical properties of non-filled degradable polymers varies between 0.9-2.5 GPa (Young’s Modulus) depending on the test method and thermal history. For comparison, the elastic modulus of cortical bone within the mid-diaphysis of a long bone is approximately 18 GPa. Another significant limitation is that semi-crystalline polyesters, PCL and PLLA, degrade very slowly. It can take years for these materials to degrade and resorb fully and the associated acidification that results often leads to inflammation. Degradable polymers that possess high moduli and relative larger degradation rates are needed for numerous regenerative medicine and orthopedic applications. α-Amino acid-based poly(ester urea)s have proven to be important materials for biomedical applications because of their excellent blood, tissue compatibility and non-toxic hydrolysis byproducts. Also, their semi-crystalline structure provides a non-chemical method to enhance their mechanical properties and processing characteristics.
Amino acid-based poly(ester urea)s are a diverse library of materials which uniquely do not lead to acidosis upon degradation. This distinct divergence from other polyester materials is likely due to the presence of the conjugate base (urea) present in each repeat unit that serve to neutralize the degrading ester linkages. The mechanical properties are three-fold higher than the highest reported values for lactic acid. My team has developed a number of non-canonical amino acid synthetic strategies, architectures and functionalization methods that further enhance the bioactivity, degradation and mechanical properties. We have extensively explored the chemical and mechanical properties of this class of material in addition to more recent work involving defining the shape memory properties using the unique hydrogen bonding properties of these materials.
In recent publications we have described the synthesis and characterization of a series of linear amino acid-based poly(ester urea)s that are strong and biodegradable. We have systematically varied the diol chain length and measured the mechanical properties and in vitro biodegradation rate of the polymers. We have found a wide ranging variation in physical and chemical properties depending on the nature of the amino acid. Some of the variations are subtle while others within simple changes in diol length can alter the Young’s modulus by as much as two orders of magnitude. We have also shown that a 1,6-hexandiol L-phenylalanine-based poly(ester urea) (poly(1-PHE-6)) possesses mechanical properties that greatly exceed commonly utilized degradable polyesters. Poly(1-PHE-6) was found to have a storage modulus of 6.8 GPa in our study, which is nearly twice the reported value of poly(lactic acid).
There has been no evidence of inflammation due to implant acidification when poly(1-PHE-6) was implanted in vivo. This trend has held up in a number of animal models including rats, rabbits and sheep. To note the utility of our materials in applications of particular relevance to the Army, a phenylalanine-based PEU material synthesized by our laboratory was used by The Methodist Hospital Research Institute in Houston as a part of a DARPA subcontract. The materials were used to repair a segmental bone defect repair in a sheep model that serves as a surrogate clinical model for injuries to warfighters due to high velocity projective injuries and improvised explosive devices. We have also initiated translational efforts in burns and blood vessel regeneration and are pursuing funding for these efforts at the appropriate agencies.
In the last year, we have completed in vivo studies in rats (vascular grafts and bone-tendon interface healing), rabbits (protein delivery from nanofibers) and sheep (segmental bone defect) and the results of these studies just being published in the literature.
These results will be the foundation of our translational research efforts over the next five years. This work is supported by the National Science Foundation, the Department of Defense, Merck and Cook Medical. The largest award to date ($6M) from the Department of Defense is a distinctive partnership with the Houston Methodist Research Institute and is designed to optimize our designs in a large sheep trial and includes a pilot exemption for use in military soldiers who present with a significant injury.
Humanitarian Benefit : The major humanitarian benefit is related to regenerative medicine in explosion related injuries and bone healing, which is described above.