MIT Biomedical Engineering Society


Vol. 4 No. 3 November 2005 National Conference Grad School Primer Langer Interview Research: hES Research: Microfluidics Photo Gallery Student Research Printable Version	The BioTECH Quarterly MIT Research Highlight Biodegradable Microfluidic Systems for Tissue Engineering By Chris Bettinger, PHD STUDENT IN MATERIALS SCI & ENGINEERING The field of tissue engineering and organ regeneration is an exciting and relatively new field of research born out of the high demand for transplants of vital organs. However, a critical limitation in the regeneration of vital organs is the lack of an intrinsic blood supply, which is required for highly vascularized organs such as the liver and kidney. Vascular features such as capillaries can be as small as 10-15 microns and have intricate geometries and precise spatial locations. Regenerated organs lack this specifically placed vasculature. These intrinsic characteristics of vasculature invite the application of microfabrication technology, which has been typically used in the production of microelectronic devices, in developing complex scaffolds that require micron-scale resolution. One thrust of research in the Langer Laboratory at MIT involves the integration of novel microfabrication techniques for vascular and liver tissue engineering applications in the context of a novel biodegradable elastomer. One important consideration in designing tissue engineering systems is the selection of a suitable biomaterial. Previous work utilizing microfabrication has used materials that are not suitable for scaffolds. Crystalline silicon and poly(di-methyl siloxane) (PDMS), while relatively biocompatible, are clearly not biodegradable, nor do they possess the proper mechanical properties that are ideal for a large implantable scaffold. In short, although these materials were not designed for tissue engineering systems, they are often employed due to their ease of fabrication. The lack of a suitable material lead Yadong Wang of the Langer Laboratory to develop poly(glycerol-sebacate) (PGS), a novel biodegradable elastomer with superior mechanical properties and biocompatibility. With this novel biomaterial in hand, the focus was to adapt typical microfabrication methods to produce microstructures using PGS. Complex three-dimensional microfluidic scaffolds were produced using fabrication techniques tailored specifically for PGS. A variety of cell types such as endothelial cells and hepatocytes were grown and sustained long-term using perfusion culture in vitro. These biodegradable microfluidic systems can be integrated with existing biomaterial systems and technologies for tissue-specific applications and increased functionality. For example, drug delivery systems, cell patterning techniques, and co-culture systems for hepatocytes can be integrated within the microchannels to promote the organization of seeded primitive cells into complex tissues. Fully biodegradable systems suitable for implantation can be fabricated by integrating flexible, small caliber PGS tubes and affixing those using additional PGS as an adhesive. The end result is an adaptable tissue engineering device that can be integrated with the patient’s existing vasculature. Working in close collaboration with Jeff Borenstein of the Micro-Electro-Mechanical Systems (MEMS) group in the Draper Laboratory and Joseph Vacanti of the Organ Fabrication Laboratory at Massachusetts General Hospital, we are continually working towards developing the next generation of implantable scaffolds that are suitable for engineering complex vascularized tissues and organs. Our long-term goals include the design and fabrication of tissue engineering systems with liver function to be used as a diagnostic tool for drug discovery or as a fully functional liver-assist device. This research was done in the Langer Research Laboratory by Chris Bettinger G in collaboration with Dr. B Orrick, Dr. Yadong Wang, Dr. Joseph Vacanti, and Dr. Jeff Borenstein. Polymer molding of microfluidic devices: Microfluidic layouts are designed using traditional engineering software such as AutoCAD (not shown) and etched into silicon to produce molds (A). Biodegradable polymers are replica molded to form sheets with microstructures (B), which can be stacked and bonded to form microfluidic devices. Three-dimensional devices were formed and sectioned (C) to verify the structure of the microfluidic channels. Devices were also perfused with fluorescent dye to demonstrate the ability of these devices to handle hydrodynamic pressures due to flow (D). Scale bars in all images are 200 microns. Comments on the Value of an Interdisciplinary Undergraduate Research Experience By Chris Bettinger, PHD STUDENT IN MATERIALS SCI & ENGINEERING Research, especially in the fields of biomedical and biological engineering, is becoming more interdisciplinary. Developing novel solutions to problems in the pharmaceutical and medical industries often requires unique approaches, which may draw upon expertise in multiple traditional disciplines. The quintessential example of the impact of using an interdisciplinary approach to solving problems can be found in the experiences of Institute Professor Robert Langer. He developed novel cancer-fighting strategies that utilized chemical engineering and materials science principles. Using this engineering-based approach, he was able to tackle and address the problem of angiogenesis in cancer tumors during the 1970s. Until that time, it was unheard of to think that an engineer would be contribute in the effort to eliminate cancer, medicine’s most daunting task. However, bringing new perspectives to old problems oftentimes leads to new exciting discoveries. With anecdotal evidence such as Prof. Langer’s experience, as well as many other professors, the importance of excelling in multiple fields of science and engineering became clear to me early on during my undergraduate career. Therefore, I studied a wide range of subjects in the physical sciences and engineering, which was a simple first step toward developing an interdisciplinary perspective. I found it is equally important, however, to engage in various UROP positions as well as industrial experience to attain adequate breadth of knowledge. In general, I found myself interested in a variety of technical fields and as a result, would never turn down the opportunity to learn. Oftentimes, it is easy to be complacent and dismiss a field of study or a branch of research simply because one is not interested or because it doesn’t seem relevant at the time. I am not arguing that one should study and work to become proficient in numerous fields because it is in fact very difficult to develop expertise in multiple disciplines. Rather, it is imperative to develop a fundamental awareness of the state of the art in various technical fields. In doing this, not only does one mature as a scientist by familiarizing oneself with a foreign topic, but one also increases the set of problem solving tools and techniques that they may draw upon in future research projects. The traditional engineering and science education is the foundation for a future scientific career. In order to maximize the potential for solving current and future technical problems, this education must be supplemented with an interest in interdisciplinary studies. The added perspective gained by these pursuits, through coursework and hands-on-experiences alike, results in a well-rounded scientific education, which more than adequately prepares undergraduate students for post-graduate degree programs.
	©2005-2006 Biomedical Engineering Society of the Massachusetts Institute of Technology. All Rights Reserved. Webmasters Connie Yee and Kenny Yan

The BioTECH Quarterly

MIT Research Highlight

Biodegradable Microfluidic Systems for Tissue Engineering

By Chris Bettinger, PHD STUDENT IN MATERIALS SCI & ENGINEERING

The field of tissue engineering and organ regeneration is an exciting and relatively new field of research born out of the high demand for transplants of vital organs. However, a critical limitation in the regeneration of vital organs is the lack of an intrinsic blood supply, which is required for highly vascularized organs such as the liver and kidney.

Vascular features such as capillaries can be as small as 10-15 microns and have intricate geometries and precise spatial locations. Regenerated organs lack this specifically placed vasculature. These intrinsic characteristics of vasculature invite the application of microfabrication technology, which has been typically used in the production of microelectronic devices, in developing complex scaffolds that require micron-scale resolution.

One thrust of research in the Langer Laboratory at MIT involves the integration of novel microfabrication techniques for vascular and liver tissue engineering applications in the context of a novel biodegradable elastomer.

One important consideration in designing tissue engineering systems is the selection of a suitable biomaterial. Previous work utilizing microfabrication has used materials that are not suitable for scaffolds. Crystalline silicon and poly(di-methyl siloxane) (PDMS), while relatively biocompatible, are clearly not biodegradable, nor do they possess the proper mechanical properties that are ideal for a large implantable scaffold. In short, although these materials were not designed for tissue engineering systems, they are often employed due to their ease of fabrication.

The lack of a suitable material lead Yadong Wang of the Langer Laboratory to develop poly(glycerol-sebacate) (PGS), a novel biodegradable elastomer with superior mechanical properties and biocompatibility. With this novel biomaterial in hand, the focus was to adapt typical microfabrication methods to produce microstructures using PGS. Complex three-dimensional microfluidic scaffolds were produced using fabrication techniques tailored specifically for PGS.

A variety of cell types such as endothelial cells and hepatocytes were grown and sustained long-term using perfusion culture in vitro. These biodegradable microfluidic systems can be integrated with existing biomaterial systems and technologies for tissue-specific applications and increased functionality.

For example, drug delivery systems, cell patterning techniques, and co-culture systems for hepatocytes can be integrated within the microchannels to promote the organization of seeded primitive cells into complex tissues. Fully biodegradable systems suitable for implantation can be fabricated by integrating flexible, small caliber PGS tubes and affixing those using additional PGS as an adhesive. The end result is an adaptable tissue engineering device that can be integrated with the patient’s existing vasculature.

Working in close collaboration with Jeff Borenstein of the Micro-Electro-Mechanical Systems (MEMS) group in the Draper Laboratory and Joseph Vacanti of the Organ Fabrication Laboratory at Massachusetts General Hospital, we are continually working towards developing the next generation of implantable scaffolds that are suitable for engineering complex vascularized tissues and organs. Our long-term goals include the design and fabrication of tissue engineering systems with liver function to be used as a diagnostic tool for drug discovery or as a fully functional liver-assist device.

This research was done in the Langer Research Laboratory by Chris Bettinger G in collaboration with Dr. B Orrick, Dr. Yadong Wang, Dr. Joseph Vacanti, and Dr. Jeff Borenstein.

Polymer molding of microfluidic devices: Microfluidic layouts are designed using traditional engineering software such as AutoCAD (not shown) and etched into silicon to produce molds (A). Biodegradable polymers are replica molded to form sheets with microstructures (B), which can be stacked and bonded to form microfluidic devices. Three-dimensional devices were formed and sectioned (C) to verify the structure of the microfluidic channels. Devices were also perfused with fluorescent dye to demonstrate the ability of these devices to handle hydrodynamic pressures due to flow (D). Scale bars in all images are 200 microns.

Comments on the Value of an Interdisciplinary Undergraduate Research Experience

By Chris Bettinger, PHD STUDENT IN MATERIALS SCI & ENGINEERING

Research, especially in the fields of biomedical and biological engineering, is becoming more interdisciplinary. Developing novel solutions to problems in the pharmaceutical and medical industries often requires unique approaches, which may draw upon expertise in multiple traditional disciplines.

The quintessential example of the impact of using an interdisciplinary approach to solving problems can be found in the experiences of Institute Professor Robert Langer. He developed novel cancer-fighting strategies that utilized chemical engineering and materials science principles.

Using this engineering-based approach, he was able to tackle and address the problem of angiogenesis in cancer tumors during the 1970s. Until that time, it was unheard of to think that an engineer would be contribute in the effort to eliminate cancer, medicine’s most daunting task. However, bringing new perspectives to old problems oftentimes leads to new exciting discoveries.

With anecdotal evidence such as Prof. Langer’s experience, as well as many other professors, the importance of excelling in multiple fields of science and engineering became clear to me early on during my undergraduate career. Therefore, I studied a wide range of subjects in the physical sciences and engineering, which was a simple first step toward developing an interdisciplinary perspective.

I found it is equally important, however, to engage in various UROP positions as well as industrial experience to attain adequate breadth of knowledge. In general, I found myself interested in a variety of technical fields and as a result, would never turn down the opportunity to learn. Oftentimes, it is easy to be complacent and dismiss a field of study or a branch of research simply because one is not interested or because it doesn’t seem relevant at the time.

I am not arguing that one should study and work to become proficient in numerous fields because it is in fact very difficult to develop expertise in multiple disciplines. Rather, it is imperative to develop a fundamental awareness of the state of the art in various technical fields. In doing this, not only does one mature as a scientist by familiarizing oneself with a foreign topic, but one also increases the set of problem solving tools and techniques that they may draw upon in future research projects.

The traditional engineering and science education is the foundation for a future scientific career. In order to maximize the potential for solving current and future technical problems, this education must be supplemented with an interest in interdisciplinary studies. The added perspective gained by these pursuits, through coursework and hands-on-experiences alike, results in a well-rounded scientific education, which more than adequately prepares undergraduate students for post-graduate degree programs.