The Tissue Engineering & Biomaterials Laboratory is located within the Fischell Department of Bioengineering at the University of Maryland. Our lab uses the principles of both engineering and life sciences to develop biomaterials that improve the quality of life of ill or injured patients. We begin with polymer science methods to synthesize novel hydrolytically degradable polymers and then fabricate these polymers into easily implantable biomaterials. Molecular and cellular biology principles are then incorporated to understand the interaction of cells, tissues, and higher life systems with these novel biomaterials. Areas of focus in our lab include the study of biomaterials for the delivery of therapeutics, scaffolds for orthopedic tissue engineering applications, and the interaction of biomaterials and tissues. Please use this site as both a window into the work and personnel at the Tissue Engineering & Biomaterials Laboratory as well as a gateway to bioengineering, cell biology, and biomaterials research.
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
A new study written by a team from the Center for Engineering Complex Tissues (CECT) will soon be published in the journal Biomaterials. The study looks into the process of developing a 3D-printed aggrecan functionalized scaffold in order to aid with microfracture procedures. The study’s aggrecan functionalized scaffold showed better improvement of regenerated cartilage tissue than those treated with traditional methods or left untreated. The study was a collaboration between Dr. Jonathan D. Packer from the Department of Orthopaedics at the University of Maryland School of Medicine in Baltimore and departments within the University of Maryland in College Park, MD. Other researchers included Ting Guo, Maeesha Noshin, Hannah Baker, Evin Taskoy, Sean J. Meredith, Qinggong Tang, Julia P. Ringel, Max Lerman, Yu Chen, and John P. Fisher.
While millions of Americans are impacted by cartilage defects, the current treatment (Microfracture and Autologous Chondrocyte Implantation) has many post-surgical difficulties and a long recovery time. This method involves drilling the layer of bone just beneath the cartilage defect to release mesenchymal stem cells (MSCs). This often leads to a weaker regenerated tissue than healthy cartilage. The new aggrecan functionalized scaffold method used in the study resulted in histologically healthier and thicker cartilage tissue formation compared to the original method.
After further examination, the team found that the aggrecan functionalized scaffold led to higher cell adhesion than control groups. For the first time in the field, the team also evaluated the cartilage regeneration at a functional level through a newly designed locomotion test. Despite this, the aggrecan functionalized scaffolds had a more even distribution of newly formed cartilage that was significantly thicker than the other groups. It also showed better chondrocytes growth and ECM formation.
When asked about the impact of the study, lead author Ting Guo said, “The presented biofunctionalized acellular scaffold combined with microfracture shows promise for clinical translation. Such acellular technologies stand to greatly impact future clinical solutions to improve the quality of repaired cartilage tissue as demonstrated in this study without additional surgeries and with a relatively low cost compared to cell-based therapies.”
This study showed that using an aggrecan functionalized scaffold can lead to better support for people undergoing treatment for articular cartilage defects, as demonstrated by improved tissue quality. This provides another possible and more efficient treatment method to study and utilize for the millions of patients affected by articular cartilage issues.
On Friday, October 12, 2018, TEBL member Charlotte Piard gave a presentation at the 3rd annual 3D Printing and Bioprinting in Healthcare Conference in Brussels, Belgium. The presentation was entitled “Biomimetic Cell-Laden 3D Printed Scaffolds for Bone Tissue Engineering.” During the presentation, Charlotte presented her research as well as an overview of other TEBL lab research topics. The conference gathers 3D printing industry leaders, business heads, medical consultants, researchers and engineers from across the globe. More information about the event can be found here.
TEBL member Javier Navarro spoke at the IX Seminary on Biomedical Engineering (SIB) at the Universidad de Los Andes in Bogotá, Colombia. The event took place May 16 – 19, 2018. Javier’s talk was entitled “Assessment of the Effects of Energy Density in Crosslinking of Keratin-Based Photo-Sensitive Resin.”
The presentation was about keratin and the creation of a resin designed for 3D printing keratin. This resin was then used to determine how much energy projected during curing defines different properties of keratin hydrogels. Navarro and other TEBL members Jay Swayambunathan, Marco Santoro, and John P. Fisher found that energy density regulated the chemical reaction needed to crosslink keratin and determines how much the hydrogels crosslink. This, when taken together with its saturation nature, determine microstructural properties of the hydrogel. By understanding the role of energy density in creating the crosslinked network, they were able to adjust the printing parameters of the resin in a cDLP 3D printing system.
For more information, the IEEE proceedings article can be found here.
TEBL lab member Navein Arumugasaamy was awarded 3rd Place for the SYIS Oral Presentation Award at the TERMIS World Congress. The award was for his presentation given during the conference, which took place September 4 – 7, 2018 in Kyoto, Japan.
The presentation was entitled “A Placenta-Fetus Model to Evaluate Maternal-Fetal Transmission and Fetal Neural Toxicitiy of Zika Virus.” The topic of the talk relates to recent TEBL publication “Biomimetic Placenta-Fetus Model Demonstrating Maternal-Fetal Transmission and Fetal Neural Toxicity of Zika Virus.” When asked about the award, Arumugasaamy shared, “It’s wonderful to be recognized for our project assessing Zika Virus effects with a placental barrier tissue model, and I’m humbled by the award. It was a great team effort across multiple labs and institutions, and I’m very appreciative of the opportunity to present our work and have it so well received.” Congratulations, Navein!
Journal of Biomedical Materials Research has recently announced that “Collagen Hydrogel Scaffold Promotes Mesenchymal Stem Cell and Endothelial Cell Coculture for Bone Tissue Engineering” was one of the journal’s top 20 most downloaded recent papers. The journal examined the number of downloads within the first 12 months of online publication for papers published between July 2016 and June 2018. The article was written by TEBL members Bao-Ngoc B. Nguyen, Rebecca Moriarty, Tim Kamalitdinov, Julie M. Etheridge, and John P. Fisher and looks at the role of collagen hydrogel scaffolds and microenvironments in bone tissue engineering. This article helped advance the field of tissue engineering as well as brought visibility to both the journal and our lab. Congratulations, Bao, Becca, Tim, Julie, and John!
Sarah Van Belleghem was awarded Most Innovative Graduate Student Presentation at the Fischell Department of Bioengineering’s annual retreat, which took place on Wednesday, August 22.
Her presentation was entitled ““Development of a 3D Printing Strategy for the Reconstruction of Nipple-Areola Complexes for Breast Cancer Survivors”
The Center for Engineering Complex Tissues (CECT) has officially launched its new website!
The CECT is a NIBIB/NIH Biomedical Technology Research Center (BTRC) aiming to grow the 3D printing and bioprinting community. It is a joint effort between TEBL at the University of Maryland with the Biomaterials Lab at Rice University and Wake Forest Institute for Regenerative Medicine (WFIRM) at Wake Forest University. The Center is headed by TEBL PI Dr. John Fisher and features projects building on our previous work developing a tubular perfusion system (TPS) bioreactor that enables human mesenchymal stem cell expansion, their osteoblastic differentiation, and subsequent formation of boney tissue.
More information about the Center and its new website can be found here.