REGENERATIVE DENTISTRY
BOTTINO LAB

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

Marco C. Bottino
DDS, MSc, PhD, FADM

DIRECTOR

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

Principal Investigator

Marco C. Bottino, DDS, MSc, PhD, FADM, holds the position of Associate Professor (tenured) in the Department of Cariology, Restorative Sciences, and Endodontics. Before joining the University of Michigan, he was Associate Professor of Biomedical and Applied Sciences and Graduate Program Director in Dental Biomaterials at Indiana University School of Dentistry. He received his Doctorate of Dental Science (DDS) degree in 2001 from Universidade Paulista (São Paulo, Brazil), his master’s degree in Nuclear Technology in 2005 from the University of São Paulo (Institute for Energy & Nuclear Research, São Paulo, Brazil), and his doctorate in Materials Science in 2010 from The University of Alabama at Birmingham (Birmingham, AL). Marco has received Young Investigator Awards from the International Association for Dental Research (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. He has served as a member of National Institutes of Health (NIH) study sections and has been the principal investigator for several NIH, foundations, and industry grants. Marco is an elected Fellow of the Academy of Dental Materials (ADM) and the Vice-President of the Dental Materials Group of the IADR. Marco is a member of the editorial board of several journals. His research interests are in the design and synthesis of tissue scaffolds, drug delivery systems, and stem cell therapies to regenerate dental, oral, and craniofacial tissues. His current research foci are the development of drug delivery system for ablating oral infection, injectable scaffolds for pulp-dentin complex regeneration, as well as multiphasic and tissue specific scaffolds for periodontal tissue reconstruction. More recently, with the acquisition of a unique BioPrinting platform, his laboratory will continue to expand the regenerative dentistry program to address other oral and craniofacial challenges.

ABOUT

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.

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.

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 list of publications

PEOPLE

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

Principal Investigator

mbottino@umich.edu

Jinping Xu, MD

Lab Specialist

jpxu@umich.edu

Nilesh Dubey, BDS, PhD

Postdoctoral Researcher

nileshkumar_dubey25@u.nus.edu

Jessica Ferreira, DDS, MSc, PhD(c)

Postdoctoral Researcher

jessaf@umich.edu

Arwa Daghrery, BDS, MSD

Graduate Student (OHS/PhD)

daghrery@umich.edu

Christina Li

Undergraduate Researcher

cgli@umich.edu

CONTACT

Regenerative Dentistry
Bottino Lab

1011 N. University, Room 5224
Ann Arbor, MI 48109-1078
mbottino@umich.edu
734-763-2206