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Faculty Profile: Dr. Marco Bottino

Advancing biomaterials for regenerative tissue applications

Dr. Marco Bottino is the Robert W. Browne Endowed Professor of Dentistry in the Department of Cariology, Restorative Sciences, and Endodontics (CRSE). He is CRSE’s Director of Research and Director of the Postgraduate Program in Regenerative Dentistry. An internationally recognized leader in the field of regenerative medicine, he investigates clinically relevant biofabrication strategies for engineering dental, oral, and craniofacial tissues, with a focus on the development of personalized therapeutics for periodontal tissue regeneration. He has received extramural funding from the National Institutes of Health (NIH), foundations, and private industry. Bottino joined the dental school in 2017 after a previous faculty position at Indiana University School of Dentistry. He has published regularly and received awards for research excellence and mentorship from national and international organizations. He has served on numerous grant review panels of the NIH and held leadership positions within the International Association for Dental Research. He is a frequent reviewer for journals in regenerative medicine and biomaterials. In the following question-and-answer interview, he provides insight into his work.

Dr. Marco Bottino

Q: You began your career path with a DDS degree. Why did you redirect to the scientific research side of oral health?

A: I had the opportunity to complete several research projects while in dental school in the field of restorative dentistry. That was when I decided to pursue a clinician-scientist academic career with a focus on the development of novel biomaterials and drug delivery therapeutics for dental tissue regeneration. I practiced general dentistry for a few years and then went to graduate school to deepen my knowledge of engineering and designing aspects of creating biomaterials for regenerative applications.

Q: Your lab uses engineering tools such as nanotechnology, biofabrication and stem cell therapies to develop biologically active biomaterial scaffolds that enhance the regeneration of damaged periodontal tissue. How are these new technologies, such as 3D printing and bioprinting, enhancing your research?

A: Successful and predictable reconstruction of tissues and organs lost due to disease, trauma or congenital anomalies remains a major challenge in dentistry and medicine. Recent strides in tissue engineering include unraveling the role of stem cells, biological signals and scaffolds in building functional tissues. Biofabrication uses 3D printing technologies to engineer biologically functional and highly organized structures, primarily using biomaterials and cells, that can be used to treat periodontitis. Our research group is focused on developing patient-specific solutions to support the regeneration of multiple tissues affected by periodontitis. We are using 3D bioprinting technologies to create patient-specific grafts based on patient imaging data from Cone Beam Computed Tomography to amplify the regeneration of periodontal tissues.

Q: Another of your lab’s research areas is developing injectable collagen-based hydrogels. How are these biocompatible materials used after root canals to support the regeneration of the pulp and dentin in necrotic immature permanent teeth?

A: Traditional therapeutics of necrotic immature permanent teeth allow for infection control but support neither root development nor restoration of the immunocompetence of the pulp. Over the last decade, we have been working on synthesizing highly tunable collagen scaffolds that can be incorporated with the patient’s stem cells to encourage dentin and pulp regeneration. Our strategy is to inject these stem cell-laden collagen scaffolds into root canals of devitalized immature permanent teeth to instruct simultaneous pulp-dentin tissue regeneration. The resulting data are informing novel regenerative-based therapeutics to treat necrotic immature permanent teeth and, thus, the potential of prolonging the use of natural dentition.

Proposed model for pulp regeneration.

Q: You have a robust track record of publications, grants, and awards. This year you’ve had more than 18 publications in numerous important scientific journals, including the American Chemical Society Applied Materials and Interfaces, Biomaterials Advances, Bioactive Materials, Acta Biomaterialia, and Journal of Materials Chemistry B, among others. From your latest research findings, what areas are you most excited about?

A: My guiding principle for high-impact research is that it should be founded on addressing real-world needs, developed using combined scientific principles, and delivered through collaborative translational approaches. Translating research to clinical implementation is of the utmost importance and public relevance. As an example, a few years ago, I was approached by a start-up company (Matregenix in Irvine, California) to validate the pre-clinical efficacy of their proprietary polymeric membrane for guided bone regeneration. This collaboration successfully resulted in funding support from the NIH/NIDCR and the preparation of a premarket submission to the Food and Drug Administration. We are now waiting to learn if we will secure the next level of funding to expedite the translation of this technology to the clinics.

Q: Your research grants and published papers always have a significant number of collaborators, often from around the world. How important is collaboration in your work?

A: I highly value the intellectual stimulation from working with a diverse group of faculty, staff, and students. My laboratory aims to provide an inclusive and integrated platform to train motivated students, including those from diverse and underrepresented backgrounds, and foster facultydriven interdisciplinary collaboration. That includes faculty colleagues at the School of Dentistry and others working nationally and internationally. Also, here at U-M, we are currently in the process of establishing a campus-wide Biofabrication Center to enable training and collaboration in this fast-evolving field. While U-M offers access to traditional 3D printers for manufacturing 3D shapes/objects and prototypes of prosthetics, our laboratory at the School of Dentistry was the first on campus to house a highly translatable biofabrication platform. Now, we can engineer personalized 3D complex living tissues because it has the capacity to converge cell-printing technologies with sophisticated biofabrication tools (ceramic printing, for example). The long-term goal of my research program is to provide an inclusive and collaborative environment to develop enabling technologies that advance diagnostic and therapeutic discoveries for treating dental, oral, and craniofacial-related diseases.

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