title: Microfluidics co-culture systems for studying tooth innervation.
abstract: Innervation plays a key role in the development and homeostasis of organs and tissues of the orofacial complex. Among these structures, teeth are peculiar organs as they are not innervated until later stages of development. Furthermore, the implication of neurons in tooth initiation, morphogenesis and differentiation is still controversial. Co-cultures constitute a valuable method to investigate and manipulate the interactions of nerve fibers with their target organs in a controlled and isolated environment. Conventional co-cultures between neurons and their target tissues have already been performed, but these cultures do not offer optimal conditions that are closely mimicking the in vivo situation. Indeed, specific cell populations require different culture media in order to preserve their physiological properties. In this study we evaluate the usefulness of a microfluidics system for co-culturing mouse trigeminal ganglia and developing teeth. This device allows the application of specific media for the appropriate development of both neuronal and dental tissues. The results show that mouse trigeminal ganglia and teeth survive for long culture periods in this microfluidics system, and that teeth maintain the attractive or repulsive effect on trigeminal neurites that has been observed in vivo. Neurites are repealed when co-cultured with embryonic tooth germs, while postnatal teeth exert an attractive effect to trigeminal ganglia-derived neurons. In conclusion, microfluidics system devices provide a valuable tool for studying the behavior of neurons during the development of orofacial tissues and organs, faithfully imitating the in vivo situation.
authors.affiliation: Department of Orofacial Development and Regeneration, Faculty of Medicine, Centre for Dental Medicine, Institute of Oral Biology, University of Zurich Zurich, Switzerland.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Pagella
authors.affiliation: NEW Therapies Group, INEB - Instituto de Engenharia Biomédica, Universidade do Porto Porto, Portugal ; Faculdade de Medicina da Universidade do Porto Porto, Portugal.
authors.forename: Estrela
authors.initials: E
authors.lastname: Neto
authors.affiliation: Department of Orofacial Development and Regeneration, Faculty of Medicine, Centre for Dental Medicine, Institute of Oral Biology, University of Zurich Zurich, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Jiménez-Rojo
authors.affiliation: NEW Therapies Group, INEB - Instituto de Engenharia Biomédica, Universidade do Porto Porto, Portugal ; Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto Porto, Portugal.
authors.forename: Meriem
authors.initials: M
authors.lastname: Lamghari
authors.affiliation: Department of Orofacial Development and Regeneration, Faculty of Medicine, Centre for Dental Medicine, Institute of Oral Biology, University of Zurich Zurich, Switzerland.
authors.forename: Thimios A
authors.initials: TA
authors.lastname: Mitsiadis
keywords: dental mesenchyme; innervation; microfluidics; mineralization; orofacial; tooth development; trigeminal ganglia