Tissue engineering of the peripheral nervous system

Abstract

The structure and function of peripheral nerves can be affected by a range of conditions with severe consequences in these patients. Currently, there are several surgical techniques available to treat peripheral nerve defects. Direct repair is the preferred treatment for short nerve gaps, and nerve autografting is the gold standard in critical nerve defects. The autografting is not always available, and the use of allograft, decellularized allograft and nerve conduits are often used with variable success. During the recent years, several outcomes were achieved in peripheral nerve tissue engineering. Promising experimental results have been demonstrated with this novel generation of nerve conduits, mainly composed by biodegradables materials in combination with intraluminal fillers, growth factors and different cell sources.

Keywords::

• biomaterials
• cell-based therapy
• graft-based repair
• surgical nerve repair
• tissue engineering
• traumatic nerve injuries
• tubulization

Financial & competing interests disclosure

This study was supported by the Spanish Ministry of Economy and Competitiveness, grant IPT-2011-0742-900000 (INNPACTO program), co-financed by Fondo Europeo de Desarrollo regional (FEDER), EU. V Carriel is supported by the grant of excellence P10-CTS 6060 from the Junta de Andalucía, Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

The authors are grateful to Ariane Ruyffelaert from the Department of Linguistics, Ghent University, Belgium for assistance with the English of this manuscript.

Key issues

• The peripheral nervous system has the capacity to regenerate its distal components following a physical disruption.

• According to the structural affection, there are five degrees of nerve injuries, and the surgical nerve reconstruction is the unique alternative to treat severe nerve injuries (fourth and fifth degrees of injuries).

• Direct surgical repair is the preferred and most efficient method for the surgical treatment of short nerve defects, but comparable or better results are achieved by the use of tubulization technique.

• In case of nerve injuries with loss of substance, the interposition of a nerve autograft or allograft is required. The nerve autograft is the most effective, providing a natural extracellular matrix, growth factors and viable Schwann cells. However, there are several associated disadvantages and they are not always clinically available.

• Clinically, decellularized nerve allograft and artificial nerve conduits (NC) are used to bridge different nerve gaps in replacement of the conventional surgical techniques and the use of graft materials. Decellularized nerve allograft is successfully used to bridge critical nerve gaps, while NC are limited to short nerve gaps with a maximum length of 3 cm.

• Experimentally, a novel regeneration of NC composed of highly aligned biodegradable biomaterials promotes efficient nerve regeneration. They guide and direct the nerve regeneration and sometimes comparable results to the nerve autograft are obtained.

• Cell-based therapy promotes a significant increase of nerve regeneration. The Schwann cells or mesenchymal stem cells are combined with soft biomaterials and are used to fill biodegradable NC.

• Mesenchymal stem cells are one of the most promising alternatives to repair nerve defects. They have the capacity to differentiate into Schwann cells phenotype, to release growth factors and to participate in the process of nerve regeneration.

Notes