Biomaterials 27 (2006) 1425–1436
Neuro tissue engineering of glial nerve guides and the
impact of different cell types
Martin Lietz
a
, Lars Dreesmann
a
, Martin Hoss
b
, Sven Oberhoffner
b
, Burkhard Schlosshauer
a,
Ã
a
NMI Naturwissenschaftliches und Medizinisches Institut an der Universita
¨
tTu
¨
bingen, Markwiesenstr. 55, D-72770 Reutlingen, Germany
b
ITV Institut fu
¨
r Textil- und Verfahrenstechnik, Ko
¨r
schtalstr. 26, D-73770 Denkendorf, Germany
Received 4 May 2005; accepted 11 August 2005
Available online 19 September 2005
Abstract
The aim of neuro tissue engineering is to imitate biological features in order to enhance regeneration. Following lesions of peripheral nerves,
Schwann cells (SCs) reorganize to form longitudinal bands of Bu
¨
ngner (boB) which function as guides for regrowing axons. In order to imitate
boB in synthetic implants designed to bridge nerve lesions, we developed resorbable, semipermeable nerve guide conduits with microstructured
internal polymer filaments. We utilized a novel microcell chip and identified three extracellular matrix components conducive for coating non-
permissive polymer surfaces. In order to maximize SC alignment, seven different microtopographies were investigated via the silicon chip
technology. Special longitudinal microgrooves directed SC orientation and growing axons of dorsal root ganglia (DRG), thus achieving
stereotropism. When these results were applied to microgrooved polymer filaments inside nerve guide conduits, we observed highly oriented
axon growth without meandering. Since scar-forming fibroblasts could potentially interfere with axonal regrowth, triple cultures with
fibroblasts, SC and DRG were conducted. Fibroblasts positioned on the outer nanopore containing conduit wall, did not hamper neuronal
and glial differentiation inside the tube. In summary, for more rapid regrowth, functional boB can be induced by guided microtissue
engineering. By considering both the negative and positive effects of cell interactions, a more rational design of nerve implants becomes feasible.
r 2005 Elsevier Ltd. All rights reserved.
Keywords: Bands of Bu
¨
ngner; Neurite guidance; Polymer filament; Rat Schwann cell; Nerve guide
1. Introduction
Annually some 400,000 patients are subjected to
neurosurgical interventions due to neurotraumas of the
peripheral nervous system [1]. This number rises when
taking into account all patients suffering from idiopathic
damage, iatrogenic injuries, compression syndromes and
systemic diseases. Of 220,000 men diagnosed with prostata
carcinoma annually in the USA (American Cancer Society,
Inc), one-third likely face erectile dysfunction due to loss or
damage of the corresponding nerves. The vast majority of
these cases remain neurosurgically untreated.
Since the peripheral nervous system retains a consider-
able regeneration potential even in late adulthood, there
are multiple therapeutic strategies presently under investi-
gation to restore function of truncated nerves. In neurotm-
esis of peripheral nerve lesions, patients suffer from
simultaneous loss of continuity of the endo-, epi- and
perineurium. Autologous transplantations are presently the
most common treatment for this condition [2]. Typically, a
sensory nerve like the n. suralis of the lower leg is sacrificed
for the transplant. However, morbidity of the donor area,
potential infections and neuroma formation are notorious
restrictions [3,4].
For successful regeneration, restoration of the nerve
pathway is crucial. To address this requirement while
avoiding the disadvantages of autologous transplants,
synthetic nerve guides have been introduced. The first
pioneering conduits used in rodent and human trials were
composed of non-resorbable polymers based on silicone
and poly-tetrafluorethylene (Gore-Tex
s
) [5–8]. However,
potential drawbacks of non-resorbable nerve guides are
permanent fibrotic encapsulation of the implant and late
loss of functional recovery caused by progressive myelina-
tion and the resulting compression of axons within the
ARTICLE IN PRESS
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0142-9612/$ - see front matter r 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.biomaterials.2005.08.007
Ã
Corresponding author. Tel.: +49 7121 5153 20; fax: +49 7121 5153 62.
E-mail address: schlosshauer@nmi.de (B. Schlosshauer).