Bottino Lab
(Regenerative Dentistry)

The University of Michigan School of Dentistry

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ABOUT


Our long-term goal is to identify new strategies to regenerate dental, oral, and craniofacial tissues by using engineering tools and stem cells.

My lab focuses on identifying and translating regenerative materials and technologies to reestablish dental, oral, and craniofacial (DOC) tissue health. We use both in vitro and in vivo pre-clinical animal models to gain further insight into the potential clinical safety and efficacy of the developed biomaterials and overall regenerative strategies.

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Our first major research thrust focuses on using engineering tools (e.g., nanotechnology and BioFabrication) and stem cell therapies to develop biologically active biomaterial scaffolds for periodontal regeneration. Specifically, my lab is refining the synthesis of bioactive scaffolds with therapeutic properties and technologies, such as 3D printing/BioPrinting, to engineer patient-specific scaffolds/constructs to amplify hard and soft tissue periodontal regeneration.

The second major research thrust is focused on developing a localized, intracanal antimicrobial drug delivery strategy that, combined with injectable biomaterial scaffolds may lead to an increased likelihood of achieving predictable pulp regeneration. Our approach involves the use of electrospinning, a textile-based nanotechnology to create 3D antibiotic-eluting nanofibrous constructs as a biocompatible disinfection strategy. We are also working on the synthesis of highly tunable injectable collagen scaffolds to encourage dentin and pulp regeneration. The resulting data are being used to guide the development of novel regenerative-based therapeutics to treat necrotic immature permanent teeth, and thus the potential of prolonging the use of the natural dentition.

With the increased demand for more aesthetically pleasing restorations, adhesively-bonded resin composites have been employed. The third major research thrust is focused on identifying a clinically viable approach to prolong the clinical success of adhesively bonded restorations through a materials-based strategy. Our approach uses aluminosilicate clay nanotubes (Halloysite®) as a biocompatible reservoir for localized and sustained delivery of therapeutic agents to inhibit the activity of endogenous proteases and ultimately enhance the longevity of adhesively bonded restorations.

DIRECTOR

marco bottino

Marco C. Bottino, DDS, MSc, PhD, FADM
Principal Investigator

[email protected] | 734-763-2206

Dr. Bottino is the Robert W. Browne Endowed Professor of Dentistry in the Department of Cariology, Restorative Sciences, and Endodontics (CRSE) at the University of Michigan School of Dentistry (U-M). He is currently the Director of Research in CRSE and the Director of the Postgraduate Program in Regenerative Dentistry at U-M. As a principal investigator, Marco has received research grants related to regenerative medicine from the National Institutes of Health (NIH), several foundations, and private industry. He has received the International Association for Dental Research (IADR) Centennial Emerging Leader Award and was the recipient of Young Investigator Awards from the IADR Pulp Biology and Implantology Research Groups and a prestigious Mentored Clinical Scientist Research Career Development Award from the National Institute for Dental and Craniofacial Research at NIH. He also serves as the reviewer for nearly 30 journals in regenerative medicine and biomaterials and, between 2018-2023, served as a standing member of the Musculoskeletal and Tissue Engineering (MTE) study section for the NIH. Marco is an elected Fellow of the Academy of Dental Materials (ADM) and a board member. He was the 2019-2020 President of the Dental Materials Group of the IADR and is currently the President-elect of the Pulp Biology Research Group (PBRG). He has published over 140 peer-reviewed papers in drug delivery, scaffolds for pulp-dentin complex regeneration, personalized scaffolds for craniomaxillofacial bone and periodontal regeneration, and soft tissue reconstruction.

RESEARCH AREAS

Biomaterials & Biofabrication

We have previously pioneered the development of a multilayered and tissue-specific membrane via electrospinning. The innovative membrane was designed and processed to present a core layer (CL) and 2 functional surface layers (SLs) that interface with hard and soft tissues. These SLs are highly customizable and can be used as a platform for generating a wide range of membranes/scaffolds endowed with unique therapeutic properties. A series of publications reflect our efforts in the fabrication of these biomaterial scaffolds for periodontal tissue engineering. We have now expanded the focus in this area with the acquisition of a unique 3D Bioprinting platform (3DDiscoveryTM, RegenHU, Villaz-St-Pierre, Switzerland) to engineer bioactive patient-specific membranes/scaffolds to amplify hard and soft tissue regeneration.

Multilayered and tissue-specific membranes/scaffolds for periodontal regeneration. (Left) Multilayered periodontal membrane processed via electrospinning showing the details of the core layer (CL) and the functional surface layers (SL). (Right) Cross-sectional SEM micrographs of the multilayered membrane.

Antimicrobial properties of ZnO-decorated polymeric nanofibers. Transmission electron micrograph of a single PCL nanofiber incorporated with ZnO nanoparticles. Representative agar plate and data of the antibacterial activity of PCL and PCL/gelatin-based ZnO-decorated membranes against Fusobacterium nucleatum (Fn).

Three-dimensional bioprinting for applications in dental, oral, and craniofacial (DOC) tissue regeneration. 3D Bioprinting & Melt Electrospinning Writing (MESW) platform (3DDiscoveryTM, RegenHU, Villaz-St-Pierre, Switzerland). Scanning electron microscopy image of a 3D printed scaffold.

Drug Delivery

Recent estimates from the National Health and Nutrition Examination Survey show that, in the US, nearly 37% of children (aged 2–8 years) in their deciduous teeth and 58% of adolescents (aged 12–19 years) in their permanent dentition are affected by caries. A challenging problem for endodontists and pediatric dentists is the clinical management of immature permanent teeth with necrotic pulp resulting from bacterial infection or trauma. Our work on the synthesis of bioactive polymer nanofibers led us to explore the role of these drug delivery systems in the context of regenerative endodontics. Specifically, we have developed a research theme that is focused on the understanding of mechanisms related to dentin biofilm eradication through the use of innovative antibiotic-eluting 3D constructs.

Electrospun antibiotic-eluting polymeric nanofibers as a biocompatible root canal disinfection strategy. (Top) Synthesis of triple antibiotic–eluting nanofibers. Representative scanning electron micrograph (SEM) of triple antibiotic–containing fibers and 3D constructs (in yellow, superimposed on the SEM image). (Bottom) Potential clinical use of the 3D patient-specific drug delivery construct.

Antimicrobial properties of antibiotic-eluting nanofibers. Representative SEM images showing bacterial growth inhibition on the antibiotic-eluting nanofibers.

Antimicrobial activity of antibiotic-eluting nanofibers against a dual-species dentin biofilm.

Clinical translation. Placement of 3D antibiotic-eluting constructs into the root canal of a periapical lesion dog model, to act as a localized intracanal drug delivery system.

Smart Dental Biomaterials

Dental caries continues and will likely remain a global health issue for many years to come. Accordingly, one high-priority research focus of the National Institute of Dental and Craniofacial Research is on the innovations in materials for long-lasting tooth restorations. Despite remarkable advances in adhesive science, research data continue to report a significant decrease in resin-dentin bond strength over time. Simply speaking, the failure of resin restorations is believed to be due in part to collagen fibril degradation in the dentin at the adhesive resin-dentin interface by matrix metalloproteinases (MMPs). Our innovative approach has been to modify dentin resin-based adhesive with Halloysite® nanotubes not only due to the potential strengthening benefits at the bond interface, but more importantly to use as a vehicle to deliver MMP inhibitors to prolong resin-dentin bond durability.

Halloysite®-modified adhesives. (A) As-received Halloysite® nanotubes (HNTs). (B) Transmission electron microscopy image showing the overall structure and the nanotubes’ hollow nature. (C) Representative scanning electron micrograph of resin–dentin interface obtained using a HNT-modified adhesive. Note the presence of agglomerated HNT on resin tags (RT).

Antimicrobial and cytocompatibility of doxycycline (DOX) loaded nanotube-modified adhesives. (A-B) Representative images of agar diffusion data of the control (SBMP) and modified adhesive disks against S. mutans (a) and L. casei (b). (C) Viability of human dental pulp stem cells (hDPSCs) exposed to eluates of the control (SBMP) and modified adhesives.

Kinetics of DOX release and MMP inhibition. (Left) Cumulative release profile (μg, mean ± SE) of the DOX-loaded nanotube-modified adhesives determined by mass spectrometry. (Right) Inhibition of MMP-1 by DOX-containing eluates (%, mean ± SE) compared to the negative control (Tris buffer).

PUBLICATIONS

The most recent publications are reported below.

View the complete listing of publications.

TEAM

Marco C. Bottino, DDS, MSc, PhD, FADM

Marco C. Bottino, DDS, MSc, PhD, FADM
Principal Investigator

[email protected]

Jinping Xu, MD

Jinping Xu, MD
Lab Specialist

[email protected]

Maedeh Rahimnejad

Maedeh Rahimnejad
Postdoctoral Researcher

[email protected]

Renan Dal Fabbro

Renan Dal Fabbro
Postdoctoral Researcher

[email protected]

sarah chang

Sarah Chang
Undergraduate Researcher

[email protected]

Ashley Silverberg

Ashley Silverberg
Undergraduate Researcher

[email protected]

CONTACT

Bottino Lab
University of Michigan School of Dentistry
1011 N University Ave, Room 2310 G
Ann Arbor, MI 48109
734-763-2206 | [email protected]