News

Congratulations to Manny Ramirez-Garcia for being awarded a Center for Visual Science T32 training fellowship!

Congratulation to Harrah Newman for winning the 2018 Charles L. Newton Award for undergraduate research and the President's Award at the 2018 Undergraduate Research Expo for her project, “Viscoelastic Heating of Bovine Intervertebral Disc.” More than 60 students participated in the exposition this year, representing some of the “most accomplished undergraduate research throughout the college,” said Paul Burgett, vice president and senior advisor to the president, who presented several awards to students. “We like to honor those whose work is on the tip of the spear, so to speak; those whose work is groundbreaking and transformative.” More information on the Undergraduate research expo can be found here.

Louisa Buckley, accompanied by her sister Rosemary — daughters of assistant professor Mark Buckley — helps a team of biomedical engineering seniors test out a prototype of their early childhood mobility device. (University of Rochester photo / J. Adam Fenster)

Making their mark: This is one in a series of profiles celebrating members of Rochester’s graduating class of 2018.

For young children with Down syndrome, cerebral palsy, and other developmental disabilities, learning to walk can be a long-term process. And in the meantime, the children find it hard to keep up with their peers, which increases their social isolation.

A team of biomedical engineering majors, working with Leah Talbot, a Rochester area physical therapist, believes it can address both issues with an inexpensive, “hybrid” walker that will be portable enough to accompany the children wherever they go.

“This is right up our alley,” says Joe Cappotelli ’18, whose senior design project teammates are Hyun Choi ’18, Devon Foggio ’18, and Daniel Myers ’18. “We’re all in the biomechanics track of biomedical engineering. And it’s a fun project, to be able to think about ways we could help these children in the future.”

When the team surveyed what is currently available, they found “go-baby-go” cars — ordinary toy cars turned into personalized vehicles for young children with disabilities. These enable the 3- to 5-year-olds to keep up with their peers, but aren’t that helpful from a therapeutic standpoint, because they don’t require the children to actually propel themselves.

Walkers used in clinical settings, on the other hand, are often bulky and expensive: great for therapy, but not for keeping up with more mobile playmates, or for taking home.

“We’ve created sort of a hybrid of the two,” says Myers. “This allows them to move around but also practice walking at the same time.” And, Foggio adds, at a more reasonable cost compared to the therapeutic devices used in clinical settings, which range from $700 to $1,200. The walker the students have designed would only cost $150 to 200, they estimate. “We wanted to find an in between,” Foggio says.

The walker consists of a frame of relatively light-weight plastic tubing, an adjustable harness in the center to support the child, steering column, and a motor/gear box/rear axle assembly to propel it.

Professor Mark Buckley has received an NIH Research Project Grant (R01) for his project, "Modulation of Insertional Achilles Tendinopathy by Multiaxial Mechanical Strains.” Insertional Achilles tendinopathy (IAT) is a common and painful disease that responds poorly to conservative (i.e., non-operative) care. Improved outcomes for IAT patients require interventions that target its fundamental cause. Thus, this study aims to elucidate the patterns of mechanical strain (i.e., deformation) that cause and reverse IAT in vitro, and determine how to induce these strain patterns in vivo through exercise-based physical therapy. The findings of this study will motivate effective, targeted non-surgical therapies for IAT. Collaborators for this project include Alayna Loiselle (Orthopaedics and CMSR), Michael Richards (Surgery), Sam Flemister (Orthopaedics), John Ketz (Orthopaedics) and Tongtong Wu (Biostatistics).

Professor Buckley has been awarded a 2017 University Research Award to pursue a promising project that has the potential to eventually leverage external funding. He will evaluate two approaches to minimizing the loss of corneal endothelial cells during cornea transplants. The project is titled, "Protection of corneal endothelial cells from surgical trauma."

Abstract:

More than 65,000 vision-restoring corneal transplantations take place every year for individuals with corneal disease, corneal injury (e.g., from cataract surgery) and corneal scarring. Unfortunately, 30% of corneal grafts fail within 20 years. The most common reason for transplanted corneal grafts to fail is loss of corneal endothelial cells (CECs), the cells that line the inside of the cornea and pump fluid from it to maintain its transparency. Many of these cells are killed due to contact with tools and other materials during transplantation surgery. Thus, there is a need for new approaches that prevent CEC death during corneal grafting.

Using a custom testing platform developed in our laboratory, our preliminary experiments suggest that changes in the cytoskeleton (the network of structures within a cell that give it its shape) of CECs greatly protect these cells from injury due to mechanical contact. That is, when cells contain fewer stress fibers -- thick cytoskeletal filaments that, like muscle, exert a contractile force -- mechanical vulnerability is reduced. Based on these findings, we hypothesize treatments known to reduce the presence of stress fibers in cells will protect CECs from mechanical injury during corneal transplantation. In Aim 1, we will test whether chemical treatment with three agents that interfere with stress fibers -- BAPTA, blebbistatin and the anti-metabolite 5-fluorouracil -- reduces CEC death when the endothelium is contacted with a controlled force (simulating surgical manipulation). In Aim 2, motivated by the previous finding that fewer CEC stress fibers are observed in corneas preserved at low temperatures, we will test whether CECs are less vulnerable to mechanical trauma when the cornea is colder. This study is a key first step towards establishing chemical treatments (Aim 1) and maintenance of the cornea at cold temperatures during surgery (Aim 2) as promising methods to limit surgical trauma-associated CEC loss during corneal transplantation and reduce risk of graft failure. These approaches may also be applicable to other eye surgeries that can damage the corneal endothelium, including cataract surgery.

Professor Mark Buckley has received a pilot grant from the Center for Musculoskeletal Research for his research project, "The influence of chondrocyte mechano-protective adaptation on the progression of osteoarthritis.” Osteoarthritis (OA) – a painful and complex joint disease characterized by progressive degeneration of articular cartilage and surrounding tissues – is among the leading causes of disability in the United States. Yet, there are no FDA-approved treatments proven to stop or reverse OA and preserve joint health, suggesting that novel targets for OA interventions are needed. Though the complete etiology of OA is unknown, aberrant mechanical loads leading to cell death and catabolic activity are thought play a role in this pathology. To maintain homeostasis when confronted by sustained biochemical stimuli, cells have a well-characterized ability to moderate their response to these signals (e.g., through downregulation of a surface receptor). The Buckley lab's preliminary data suggests that chondrocytes can also rapidly moderate their sensitivity to sustained mechanical stimuli (e.g., during ambulation) to prevent cell death or abnormal (pathological) behavior. Hence, it may be possible to prevent or slow OA by enhancing this adaptive phenomenon, which we refer to herein as cytoprotective adaptation to mechanical stimuli (CAMS).

The lab's long-term goal is to develop translatable therapies that protect cartilage from degeneration through stimulation or enhancement of CAMS. To take the next step towards this goal, the objective herein is to rigorously characterize our in vivo cartilage injury model and employ this model to assess how CAMS impacts long-term OA progression. Based on the lab's preliminary data, the central hypothesis is that CAMS slows OA pathogenesis following a traumatic joint injury. The rationale for the proposed study is that identifying CAMS as a chondroprotective cellular process address the need for identification of new and promising targets of OA interventions.

Congratulations to Manuel Ramirez, a graduate student in the lab of Mark Buckley, who was awarded a summer fellowship from the Fight for Sight Foundation.

Summer Student Fellowships are available to undergraduates, graduate and medical students who are interested in pursuing eye-related clinical or basic research. FFS occupies a unique niche in the eye research foundation community -- its primary mission is to support and encourage promising scientists early in their careers.

Fight for Sight (FFS) was founded in 1946 by Mildred Weisenfeld, a young woman with retinitis pigmentosa, to encourage and fund research in ophthalmology, vision and related sciences. The goal of Fight for Sight is to encourage and facilitate research in detection, understanding, prevention, treatment and cures of visual disorders, especially those diseases leading to impaired sight or blindness.

Congratulations to BME Professors Mark Buckley and Catherine K. Kuo whose project will receive a University Research award this year. University Research Awards, previously known as Provost Multidisciplinary Awards, provide seed money on a competitive basis for innovative research projects that are likely to attract external support when sufficiently developed. Below is a description of their research project:

Role of Mechanics in Etiology of Congenital Talipes Equinovarus: Catherine K. Kuo, Associate Professor of Biomedical Engineering; Mark Buckley, Assistant Professor of Biomedical Engineering; and Natasha O'Malley, Assistant Professor of Orthopaedics.

To develop novel in vitro and in vivo experimental models to investigate the role of aberrant mechanical loading of embryonic tendons in the development of clubfoot. The findings of this study will help motivate novel prevention or treatment strategies for nearly 200,000 babies born with clubfoot each year.

BME Professor Mark Buckley and his collaborators A. Samuel Flemister (Orthopaedics), Alayna Loiselle (Center for Musculoskeletal Research) and Michael Richards (Surgery) were awarded a 2016 AOFAS Research Grant earlier this month for their project entitled, “In Vitro Assessment of the Role of Mechanical Strain in the Pathogenesis and Reversal of Insertional Achilles Tendinopathy.” This was announced at AOFAS Specialty Day on March 5 in Orlando, Florida. Insertional Achilles tendinopathy (IAT) is a common and painful disorder that responds poorly to conservative (i.e., non-operative) care. Improved outcomes for IAT patients require interventions that target the fundamental causes of the disease. Thus, this study seeks to elucidate 1) how mechanical deformations occurring in the Achilles tendon insertion can lead to IAT pathogenesis (using an in vitro model); and 2) whether the IAT associated changes can be reversed in vitro by specific mechanical loading regimens. The findings of this study will motivate effective, targeted non-surgical therapies for IAT.

Eric Comeau is the recipient of an American Heart Association Pre-Doctoral Fellowship. The fellowship will support Eric's project titled "Ultrasound standing wave field technologies for cell patterning and microvessel network formation in vitro and in situ". Through this project, Eric will advance new ultrasound technologies for tissue engineering applications. Eric is a graduate student in the Department of Biomedical Engineering and is co-mentored by Professor Diane Dalecki (BME) and Professor Denise C. Hocking (Pharmacology and Physiology; BME). Eric is also a student member of the Rochester Center for Biomedical Ultrasound (RCBU).

BME Professor Mark Buckley has received support from the University of Rochester's Valerie and Frank Furth Fund for his proposal The Role of Mechanics in Disease and Disease Therapies.

The Furth Fund promotes natural and biological science research by funding young scientists in Arts, Sciences, & Engineering or the Medical Center. Each year, one award in the amount of $10,000 is granted to support post-doctoral and graduate students and/or to fund equipment purchases.

BME Assistant Professor Mark Buckley has received an NIH R03 grant for the project entitled "Tracking Achilles tendon compression to monitor insertional Achilles tendinopathy." Insertional Achilles tendinopathy (IAT) is a painful and common disorder that is difficult to treat. Standard physical therapy interventions that work well for other forms of Achilles tendinopathy are only ~50% effective for IAT, and patients who fail physical therapy require surgeries that are expensive, entail long recovery times and often lead to complications.

The Buckley's lab research will define a critical threshold for damaging compression in the Achilles tendon that will inform targeted orthotics, exercises and/or surgical strategies aimed at treating this disease. The results of this research may also lead to the development of an inexpensive and noninvasive tool which would enable monitoring of treatments to improve patients with IAT.

Department of Biomedical Engineering Assistant Professor Mark Buckley was awarded a pilot grant from the University of Rochester Core Center for Musculoskeletal Biology and Medicine (URCCMBM) for his research in collaboration with A. Samuel Flemister from the Department of Orthopaedics and Mike Richards from the Department of Surgery. This grant will support their research to improve treatment for insertional Achilles tendinopathy (IAT), a common and painful disease that resists standard forms of non-operative care.

The URCCMBM provides shared facilities and services to groups of established, currently funded investigators addressing scientific problems in musculoskeletal biology and medicine, in order to improve efficiency, accelerate the pace of research, and ensure greater productivity.

Jason Inzana and Dr. Hani Awad

A recent article in Hajim School of Engineering' and Applied Sciences' newsletter, The Full Spectrum, features examples of how tissue engineering research at the Biomedical Engineering Department, much of which is conducted in preclinical models to heal traumatic injuries, is bolstered by the work of BME faculty and graduate students in the laboratories of professors Awad, Benoit, and Buckley, capitalizing on close ties with the Center for Musculoskeletal Research.

As part of a consortium of research projects funded by AOTrauma, Dr. Hani Awad and his lab members are using new 3D printing technology to fabricate bone scaffolds made of biocompatible material to replace the original bone tissue lost to infection. As part of the printing process, the scaffolds can be ink-jetted with antibiotics to fight the infection and with growth factors to stimulate replacement bone growth. These therapeutics can be applied to the surface of the graft, or embedded uniformly in it, so they can be released gradually, as the graft dissolves, to ensure the infection is eradicated and to stimulate regeneration of the bone tissue.

Dr. Danielle Benoit

Dr. Mark Buckley

With support from a National Institutes of Health grant, Dr. Danielle Benoit's team is exploring the use of hydrogels - Jell-O-like polymers - that can be seeded with the patient's own stem cells and wrapped around the transplant. Benoit's graduate student Michael Hoffman has demonstrated that as the hydrogel dissolves, the stem cells are gradually released and promote bone healing and integration. Benoit is exploring various ways in which this can all be orchestrated to maximize graft healing and integration.

Dr. Mark Buckley, who joined biomedical engineering as an assistant professor at the start of the year, is studying heat buildup in tendons as they are stretched during various activities and the extent to which this contributes to cell death and eventual deterioration of the tendon. A key part of this research involves characterizing exactly what constitutes healthy tendon structure and function.