Tissue engineered nerve constructs:where do we stand?

Abstract

Driven by enormous clinical need, interest in peripheral nerve regeneration has become a prime focus of research and area of growth within the field of tissue engineering. While using autologous donor nerves for bridging peripheral defects remains today's gold standard, it remains associated with high donor site morbidity and lack of full recovery. This dictates research towards the development of biomimetic constructs as alternatives. Based on current concepts, this review summarizes various approaches including different extracellular martices, scaffolds, and growth factors that have been shown to promote migration and proliferation of Schwann cells. Since neither of these concepts in isolation is enough, although each is gaining increased interest to promote nerve regeneration, various combinations will need to be identified to strike a harmonious balance. Additional factors that must be incorporated into tissue engineered nerve constructs are also unknown and warrant further research efforts. It seems that future directions may allow us to determine the “missing link”.

Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

“…8), which may provide some early guidance cues, including growth factors (Franzen et al, 1999). This view is in contrast to the idea that fibroblasts mainly contribute to an inhibitory scar or barrier (Chalfoun et al, 2006;Yannas et al, 2007). The outer layer of fibroblasts between the regenerate and the conduit wall (Fig.…”

“…However, the VEGFsecreting MSCs did appear to stimulate new vessel growth. The optimal design of tissue-engineered nerve guides must consider not only the addition of growth factors and supportive cells to the scaffold across the gap but also the nature of the ECM (Chalfoun et al, 2006).…”

“…Certain studies have reported that regeneration was improved when glial growth factor was added (Bryan et al, 2000), when the conduit covering the lesion gap was linked with brain-derived neurotrophic factor and ciliary neurotrophic factor (Ho et al, 1998), or when there is a slow release delivery of nerve growth factor (Lee et al, 2003;Chalfoun et al, 2006). Vascular endothelial growth factor (VEGF) may also improve nerve regeneration.…”

Neuroactive conducting scaffolds: nerve growth factor conjugation on active ester-functionalized polypyrrole

“…Neurons are highly affected by the components of their environment including bioactive molecules such as neurotrophic factors, electrical signals, extracellular matrix molecules and cell-to-cell interactions (Lutolf & Hubbell 2005;Chalfoun et al 2006;Li & Hoffman-Kim 2008). As a consequence, neuronal tissue engineering has focused on how to produce optimal scaffolds by integrating multiple cues to mimic natural nerve tissue (Serini & Bussolino 2005;Zhang et al 2005;Silva 2006).…”

New treatment for peripheral nerve defects: Reconstruction of a 2 cm, monkey median nerve gap by direct lengthening of both nerve stumps

“…Research has been conducted to develop new treatment methods using neurotrophic factors, cultured cells, artificial nerves, various nerve conduits, allografts, or a combination of these in order to increase axon regenerating speed. 10 We believe that reducing the number of anastomosis sites to one is the easiest method to improve nerve regeneration in the treatment of peripheral nerve defects. This concept is fundamentally different from using artificial nerves.…”