The current focus is to better understand the role of peripheral nerves and innervation in pathology and repair of tissues and the development of 3D in vitro platform to facilitate this research. The ulimate goal is realize “neurogenic tissue repair” as a regenerative medicine strategy. Areas of interest include:
- Exploring neural dysfunction in disease models, including
- Hyperinnervation in pathological progression for diagnostics
- Pharmaceutical intervention in the treatment of disease
- The role of innervation on the intrinsic regenerative capacity of tissues
- Reinnervation of regenerated or transplanted tissues to return tissue function
This involves the use of biofabrication techniques to develop 3D co-culture environments that combine peripheral neurons (sensory, motor, sympathetic, parasympathetic) with organoids and other tissue types, preserving tissue function and the physiological nerve-tissue organization. The further incorporation of optogenetic regulation over neural activity allows for control over functionally innervated tissue.
These designed 3D co-culture systems aim to overcome deficits in current in vitro models, which do not sufficiently recapitulate the complex organization of natively innervated tissue. At the same time, this approach also avoids issues observed for in vivo models; systemic activation of neurons simultaneously affects many tissues within the body, resulting in uncontrolled systemic crosstalk that obscures the role of neural stimulation. The synergistic combination of technology and biology found within the MERLN Institute allows for the development of these essential tools to study the impact of the peripheral nervous system on tissue health, disease, and regeneration.
In addition, peripheral nerve repair remains an active area of research as well as collaboration with other researchers to create and use tailored 3D in vitro culture systems for other applications.
- Wieringa PA, Gonçalves de Pinho AR, Micera S, van Wezel RJA, Moroni L. Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies. Adv Healthc Mater. 2018;7(8):1–19, https://www.ncbi.nlm.nih.gov/pubmed/29349931
- Santos D, Wieringa P, Moroni L, Navarro X, del Valle J. PEOT/PBT guides enhance nerve regeneration in long gap defects. Adv Healthc Mater [Internet]. 2017;6(3):1600298, http://dx.doi.org/10.1002/adhm.201600298
- Masaeli E, Wieringa PA, Morshed M, Nasr-Esfahani MH, Sadri S, van Blitterswijk CA, et al. Peptide functionalized polyhydroxyalkanoate nanofibrous scaffolds enhance Schwann cells activity. Nanomedicine Nanotechnology, Biol Med [Internet]. 2014;10(7):1559–69, http://www.sciencedirect.com/science/article/pii/S1549963414002093
- Wieringa P, Tonazzini I, Micera S, Cecchini M. Nanotopography induced contact guidance of the F11 cell line during neuronal differentiation: a neuronal model cell line for tissue scaffold development. Nanotechnology [Internet]. 2012 Jul 11 [cited 2012 Sep 12];23(27):275102, http://www.ncbi.nlm.nih.gov/pubmed/22710035
- Wieringa PA, Wiertz RWF, de Weerd E, Rutten WLC. Bifurcating microchannels as a scaffold to induce separation of regenerating neurites. J Neural Eng [Internet]. 2010;7(1):016001, http://www.ncbi.nlm.nih.gov/pubmed/20054102