Maryland Engineering’s John Fisher Appointed MPower Professor

Posted on November 7, 2022 by kbradish

Fischell Family Distinguished Professor and Fischell Department of Bioengineering (BIOE) Chair John P. Fisher was named an MPower Professor by the University of Maryland Strategic Partnership: MPowering the State. Fisher is one of three University of Maryland, College Park (UMCP) faculty members to receive the honor along with three University of Maryland, Baltimore (UMB) faculty members.

Fisher was recognized for both his collaborative research efforts and the key role he played in establishing new connections between the two campuses. On the research front, Fisher most recently worked with cross-campus collaborators in the areas of stem cell culturing and tissue reconstruction for breast cancer patients. As BIOE department chair, Fisher has been instrumental in the establishment of the joint M.D./Ph.D. and M.D./M.S. programs with BIOE and the School of Medicine (UMB), as well as in the launch ofNeuro-Link, an initiative to provide funding support for joint BIOE and Department of Neurosurgery (UMB) research endeavors.

The MPower Professorship recognizes, incentivizes, and fosters collaborations between faculty who are working together on the most pressing issues of our time. To be considered for the MPower Professorship, faculty must demonstrate collaboration on strategic research that would be unattainable or difficult to achieve by UMB or UMCP acting independently of one another and must embrace the mission of MPower to collaboratively strengthen and serve the state of Maryland and its citizens.

Each professor will receive $150,000, allocated over three years, to apply to their salary or to support supplemental research activities. These funds recognize, enable, and support strong collaborations between faculty in the joint research enterprise between UMCP and UMB.

Fisher is the second BIOE faculty member in as many years to receive the honor, following Minta Martin Professor of Engineering Christopher M. Jewell in 2021.

“The MPower Professors have shown incredible dedication and commitment to collaboration, innovation and discovery. Their work to solve major challenges and positively impact the lives of others is bolstered by this investment,” said UMB President Bruce E. Jarrell, M.D.

“The six professors selected for this honor are each working across disciplines to address the most complex challenges facing society today, bridging research and scholarship between institutions to foster innovation that will impact citizens in Maryland, across the country, and around the world,” said UMCP President Darryll J. Pines.

As the director of the Tissue Engineering and Biomaterials Lab, Fisher leads his research team in investigating biomaterials, stem cells, bioprinting, and bioreactors for the regeneration of lost tissues – in particular, bone, cartilage, and cardiovascular soft tissues. Fisher’s lab has published more than 200 articles, book chapters, editorials, and proceedings and delivered more than 340 invited and contributed presentations while utilizing more than $15 million in financial support from the National Institutes of Health (NIH), the National Science Foundation, the U.S. Food and Drug Administration, the National Institute of Standards and Technology, the U.S. Department of Defense, and other institutions.

“Healthcare is a multifaceted challenge that requires collaboration from different fields: clinicians, engineers, scientists, and public health experts partnering on solutions to today’s most pressing challenges. As leaders in the scientific community, we have a responsibility to strengthen the ties that make human health innovation possible. Dr. Fisher is making good on that responsibility,” said Maryland Engineering Dean Samuel Graham, Jr. “We see Dr. Fisher’s dedication to his students, department, and the broader community every day, and we’re fortunate to benefit from his leadership at Maryland Engineering.”

In addition to his BIOE appointment, Fisher is also the director of the Center for Engineering Complex Tissue, an NIH National Institute of Biomedical Imaging and Bioengineering center established to create a broad community that focuses on 3D printing and bioprinting for regenerative medicine applications.

Fisher is an elected Fellow of the American Institute for Medical and Biological Engineering, the Biomedical Engineering Society, and the International Academy of Medical and Biological Engineering. Among his previous awards, he has received the Society for Biomaterials Clemson Award for Contributions to the Literature, the Tissue Engineering and Regenerative Medicine International Society – Americas’ Senior Scientist Award, and a Fulbright Fellowship to study at the National University of Ireland, Galway. Currently, he serves as editor-in-chief of the journal Tissue Engineering, while also editing six texts in the field of tissue engineering.

Fisher earned a B.S. in biomedical and chemical engineering from Johns Hopkins University in 1995, an M.S. in chemical engineering from the University of Cincinnati in 1998, and a Ph.D. in bioengineering from Rice University in 2003. He completed a postdoctoral fellowship in cartilage biology and engineering at the University of California, Davis in 2003.

The University of Maryland Strategic Partnership: MPowering the State leverages the sizable strengths and complementary missions of both UMB and UMCP to strengthen Maryland’s innovation economy, advance interdisciplinary research, create opportunities for students, and solve important problems for the people of Maryland and the nation. Working together, UMB and UMCP achieve innovation and impact through collaboration.

The University of Maryland Strategic Partnership Act of 2016 strengthened and formalized the structured relationship between UMB and UMCP, which began in 2012. The law deepens the alliance and enables UMB and UMCP to pursue even greater transformative change and impact, far surpassing what each institution could do independently of the other.

Story from the Fischell Department of Bioengineering.

Erfan Jabari Receives Winston Family Honors

Posted on May 10, 2022 by kbradish

Fischell Department of Bioengineering (BIOE) senior Erfan Jabari received the 2022 Winston Family Papers Award for Outstanding Honors Thesis during the University of Maryland (UMD) Honors College Citation Ceremony on Friday, April 29.

Established by Roger (’76, ’79) and Karen Winston (’75), the annual UMD Winston Honors Writing Awards recognize the best essays, research papers, and theses written by honors students.

Erfan, an undergraduate researcher in BIOE professor John Fisher’s Tissue Engineering & Biomaterials Laboratory, focused his thesis on critically-sized bone defect repair in orthopedic medicine.

“Bone tissue is naturally able to repair damage and regenerate completely, but medical intervention becomes necessary when a defect’s size is too large,” Jabari said. “Bone grafts – the current treatment option – are limited in supply and pose a significant risk of donor site morbidity or immune rejection. Bone tissue engineering aims to address these shortcomings by developing synthetic constructs that coordinate biomaterials, cells, and bioactive signals to facilitate tissue repair.”

In bone tissue engineering, mesenchymal bone-forming cells have been explored thoroughly as a tool for defect repair, he noted. The role of osteoclasts – their bone resorbing counterpart – has not been investigated as extensively. Recent bone physiology research shows, however, that osteoclasts have an interesting ability to interact with bone-forming osteoblasts and mesenchymal stem cells (MSCs) through a variety of mechanisms to stimulate bone formation. Motivated by this concept, Jabari and fellow members of Fisher’s lab sought to develop a system whereby osteoclast-directed bone formation could be observed and investigated for bone tissue engineering purposes.

“In this effort, we successfully developed a 2D coculture model of human MSCs and peripheral blood-derived monocytes (progenitors of osteoclasts),” he said. “Our system shows that bone formation is enhanced in conditions where osteoclast development is facilitated, corroborating evidence that osteoclasts support the activity of bone-forming cells. Specifically, we observed known features of osteoclast-directed bone formation such as MSC proliferation and matrix development, and a novel feature – MSC clustering.”

Ultimately, the group demonstrated the potential of osteoclasts in bone tissue engineering to inform future strategies for bone defect repair, Jabari said. The work, which revealed the ability of osteoclasts to induce MSC clustering, also provides an accessible system for further investigation of osteoclast-directed bone formation.

In addition to his Winston Family Honors Award, Jabari was also recently named one of the University of Maryland’s Undergraduate Researchers of the Year.

Jabari plans to graduate in December 2022, after which he hopes to explore an M.D./Ph.D. program.

“I am excited to expand on the experiences the Fischell Department of Bioengineering has granted me, wherever that may be!” he said.

Story from the Fischell Department of Bioengineering.

Fisher, FDA Aim to Advance Safety of Cardiac Medical Devices

Posted on May 9, 2022 by amckenn1

In recent years, the use of cardiac electrophysiology medical devices – Cardiac Resynchronization Therapy (CRT), Implantable Cardioverter Defibrillator (ICD) and Cardiac Contractility Modulation (CCM) – to treat diseased heart tissue during heart failure has increased. Such technologies have proven critical to reducing mortality and improving patient quality of life. Before these technologies can be used in patients, preclinical bench testing – including large- and small-animal testing strategies – serves a critical role in advancing understanding of device mechanisms and safety. Consequently, novel human-based preclinical models are needed to reduce the burden on animal testing and clinical trials, and hiPSCs have been heralded as a potential solution. To usher this technology into the regulatory setting, the scientific community needs to learn more about 3D-printed culture strategies and identify best practices for the robust generation of such tissues.

The Fisher Lab is collaborating with Ksenia Blinova, assistant director, and T. K. Feaster, staff fellow, of the Division of Biomedical Physics in the Office of Science and Engineering Labs in the FDA’s Center for Devices and Radiological Health, to establish standardized methods for evaluating cardiac electrophysiology medical devices in human cells at the bench. The research trio is pursuing this work as a National Science Foundation (NSF) Scholars-in-Residence project. They aim to develop new knowledge and testing tools to further timely predictivity of these technologies.

“We have all witnessed remarkable advances in cell adhesion centrifugation (CAC) and hiPSC technology,” said Fisher. “Although useful, the potential for CAC to generate 3D-printed human heart models warrants further investigation. With support from the NSF, the knowledge gained from the UMD-FDA collaboration can help facilitate the development of such models to accelerate and inform the regulatory review process.”

“This collaborative research project is intended to help fill a gap in knowledge and test methods that has become increasingly important in recent years, given the rising level of activity towards cardiac electrophysiology device-based therapy,” said Drs. Blinova and Feaster. “We are very excited to be working together to develop innovative technological approaches with the potential to improve public health.”

The NSF – through its Directorate for Engineering, the Directorate of Computer and Information Science and Engineering Division of Computer and Network Systems, and the Directorate for Mathematical and Physical Sciences Division of Materials Research – along with the FDA – through its Center for Devices and Radiological Health (CDRH) – have established the NSF/FDA Scholar-in-Residence Program at FDA. This program comprises an interagency partnership for the investigation of scientific and engineering issues concerning emerging trends in medical device technology. This partnership is designed to enable investigators in science, engineering, and computer science to develop research collaborations within the intramural research environment at the FDA.

For more information about this project and the NSF/FDA SIR program, contact OSEL_CDRH@fda.hhs.gov.

Published July 30, 2021

UMD Bioengineers Take New Approach to Engineering Heart Tissue

Posted on April 6, 2022 by amckenn1

University of Maryland professor Xiaoming (Shawn) He and fellow Fischell Department of Bioengineering (BIOE) researchers developed a new strategy to improve engineered heart tissues and one day advance overall understanding of heart disease.

According to the Centers for Disease Control and Prevention, heart disease remains the leading cause of death for both men and women in the United States. A major reason for this is that the human heart has very limited capacity to regenerate cardiomyocytes – the contractile cells of the cardiac muscle – when these cells become damaged. This damage commonly occurs due to ischemia – a reduction of blood flow to the heart, most often resulting from buildup or a blockage in the arteries.

Stem cell therapy is widely considered a promising strategy for treating heart disease. Given the significant ethical concerns associated with human embryonic stem cells, scientists look instead to use what are functionally embryonic stem cell-like cells – called human induced pluripotent stem cells (iPSCs) – to generate cardiomyocytes.

The science behind the process of tapping human iPSCs in this way is both fascinating and complex. For example, as an alternative to using human embryonic stem cells, bioengineers can take fibroblasts – the most common type of cell found in connective tissue – from a patient’s skin. They then “reprogram” these cells into iPSCs to convert – or differentiate – them into cardiomyocytes. To do this, historically, scientists have harnessed the power of viruses – such as adenoviruses – to transfer the genes they need into the harvested skin cells through the process of transduction. In this way, scientists can essentially “recode” skin cells to become cardiac muscle cells.

Unfortunately, the process poses many challenges. For one, the use of a virus or viral vector raises health concerns because of the potential for the virus to infect unintended cells in the human body. Even when scientists don’t use a virus in the reprogramming process, they face an additional hurdle. Believe it or not, iPSCs have the ability to transform into virtually any type of cell in the human body; this means that a human iPSC intended to be a cardiac muscle cell might become skin, hair, or bone instead.

Put simply: if the aim is to engineer cardiac muscle tissue, there is no room for error. A batch of human iPSCs intended for use in the heart simply cannot include an errant skin, hair, or bone cell.

But, the process of differentiating cells into cardiomyocytes can take time – as many as two weeks or more using traditional methods. In order to shorten the time frame and increase the yield of human cardiomyocytes, engineers often use 3D cell cultures rather than the conventional 2D approach. Even more, they use rho-kinase inhibitors – better known as ROCK inhibitors – to improve the survival of 3D-cultured human iPSCs before differentiating them into cardiomyocytes.

For years, engineers have accepted 10μM as the standard concentration of ROCK inhibitors for use in this process.

But years of hard work – and a little bit of luck – led Fischell Department of Bioengineering Professor Xiaoming (Shawn) He and a team of researchers to an important discovery. Their findings were published in Bioactive Materials.

He and his team found that the ROCK inhibitor commonly used in 3D cultures of human iPSCs contributed extensively to their heterogeneous differentiation. In other words, the ROCK inhibitor improved both the survival and yield of human iPSCs, but at a quality cost: the yields always included unintended cells, mixed in with cardiac muscle cells after cardiac differentiation.

“When put in 3D culture, human iPSCs easily undergo a type of cell death known as apoptosis, which can be minimized by adding 10μM ROCK inhibitor,” He said. “However, our work shows that this high concentration of ROCK inhibitor primes human iPSCs into not only the mesoderm for cardiac differentiation but also the other two germ layers –ectoderm and endoderm – for skin, hair, or bone differentiation, even before initiating cardiac differentiation.”

He and his team found that by reducing the concentration of the ROCK inhibitor to 1μM, they could dramatically improve the quality of human iPSC differentiation into cardiomyocytes. In fact, with this revised concentration, the team produced cardiac muscle cells with a beating efficiency of 95 percent in just a week, compared with when they used 10μM of the ROCK inhibitor; in the latter scenario, their yield of cardiomyocytes achieved a beating efficiency of under 50 percent in two weeks’ time. Even more, in the 1μM scenario, He’s team was able to synchronize the beating of their cardiomyocytes, creating a cardiac cell network – a cardiac spheroid – that beats at the same rate (~1 Hz) as that of the human heart. And, they did so with human iPSCs reprogrammed by a non-virus method.

“This paves the way toward producing a large number of highly pure and synchronized patient-specific cardiomyocytes for clinical use, with minimized concern on unintended tissue growth, arrhythmia, or viral infection,” He said.

Moving forward, He and his team hope to tackle the challenge of increasing their yield of 3D-cultured human iPSCs. Their work could help point to new techniques for large-scale production of human iPSCs-derived cardiomyocytes for use in engineering 3D cardiac constructs. Examples include bioprinting human hearts with therapeutic applications for heart attacks, heart transplantation, and high-fidelity drug screening of cardiotoxicity. The team’s work could also advance understanding of deadly heart diseases.

BIOE postdoctoral researcher Bin Jiang served as first author on the paper. In addition to Xiaoming (Shawn) He, BIOE postdoctoral researcher Wenquan Ou, Ph.D. students James Shamul and Samantha Stewart, visiting scholar Hao Chen, alumna Sarah Van Belleghem (Ph.D. ’21) and BIOE chair John P. Fisher also contributed to the paper, along with Zhengou Liu, M.D., Ph.D. of the University of Missouri’s Division of Cardiovascular Medicine.

Along with this work, He’s research group also develops novel strategies to bank human cells, tissues, and organs. Recently, they developed a novel natural sand-based technology to greatly improve the quality and yield of banking human iPSCs. This work is also published in Bioactive Materials.

In addition to his appointment as BIOE professor, He also holds affiliations with the UMD Marlene and Stewart Greenebaum Comprehensive Cancer Center and the UMD Robert E. Fischell Institute for Biomedical Devices.

Published February 11, 2022

Bioactive scaffolds guide sore knee relief, cartilage repair

Posted on March 25, 2019 by athomp24

NIBIB-funded researchers have developed a 3-D-printed scaffold coated in aggrecan, a native cartilage component, to improve the regeneration of cartilage tissue in joints. The scaffold was combined with a common microfracture procedure and tested in rabbits. University of Maryland researchers found the combination of the implant and microfracture procedure to be ten times more effective than microfracture alone. Microfracture alone is the standard therapy currently.

As people age, it is common for pain to develop in joints, especially in the knee joint. In 2017, reportedly close to twelve million individuals sought treatment for knee pain. Some knee pain problems arise from damaged articular cartilage, which is a rubber-like material that reduces friction in joints. Over time, articular cartilage can deteriorate or become damaged following injury or normal wear and tear, leading to the pain many people feel as they age.

Treating articular cartilage defects is challenging because cartilage tissue is non-regenerative, and implants poorly integrate with the native cartilage. One common procedure for cartilage restoration is the microfracture procedure, where damaged cartilage is removed, and small holes are created in the bone at the sites of cartilage removal. These small holes stimulate the growth of new cartilage by triggering the release of native mesenchymal stem cells (MSCs) from the bone. MSCs are the most vital factor for effective cartilage regeneration.

However, the microfracture procedure alone produces a weaker tissue in comparison to native cartilage because MSCs cannot easily locate or attach to the defect site(s). Other treatments can involve multiple surgeries or, depending on the level of damage, a total knee replacement. Lead researcher and director of the NIBIB-funded Center for Engineering Complex Tissues at the University of Maryland, John P. Fisher, Ph.D., sought to improve the quality of regenerated tissue during the microfracture procedure by developing a 3-D-printed scaffold. “Cartilage repair is a complicated research problem. Substantial progress will require a creative combination of methods and technologies to restore a material that was not meant to naturally regenerate,” said Seila Selimovic, Ph.D., director of the NIBIB program in Tissue Engineering.

“Our team, led by graduate student Ting Guo, Ph.D., who has since completed her degree, wanted to create a scaffold that could be readily translated into a clinical solution,” said Fisher. The scaffold, which can be printed in minutes, is functionalized with aggrecan to provide binding sites for cells released from the microfractures. The scaffold was tested in a well-established rabbit model for orthopedic surgery, where it was implanted over the defect site following microfracture. The scaffold guides MSCs and growth factors to the defect sites and strengthens cartilage regeneration.

Results from the study published in Biomaterials showed that the 3-D-printed scaffolds with aggrecan improved cartilage regeneration ten times more than microfracture alone or in combination with a non-functionalized scaffold. Congruently, aggrecan increased cell attachment to the scaffold by ten times in comparison to a non-functionalized scaffold—this was likely the reason why cartilage repair was improved. “Cartilage defects are a significant problem and can become a source of widespread arthritis and pain in our population. Our cartilage was not designed to function as long as we live now, so we need find ways to help it heal and improve quality of life,” says Jonathan D. Packer, M.D., collaborator and surgeon who performed the operations on the rabbits in this study.

In the future, Fisher and his team hope to optimize the functionality of the scaffold, so it selectively binds just MSCs rather than everything that gets released from the microfractures, to further strengthen the regenerated tissue. The next step involves replicating similar results to this initial study in a different animal model. Further down the road, Fisher would like to personalize each implant to a patient’s defect site by using readily available imaging already used in hospitals to pinpoint the exact size of the defect sites.

To read the research behind this article, please see: Ting Guo et al. 3D printed biofunctionalized scaffolds for microfracture repair of cartilage defects, Biomaterials (2018). DOI: 10.1016/j.biomaterials.2018.09.022