NEURO-PRINT. Fabrication of microvascularised guide conduits for the regeneration of peripheral nerves by 3D bioprinting

• Applicant: Dr. Stefan Zimmermann, since 12/2023
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 528300449

Peripheral nerve injuries are common (250,000 cases/year in the US alone) and often result in persistent paresis and loss of sensitivity. Poor functional outcomes can be expected especially in the case of injuries with a longer defect distance. Such injuries are treated by a nerve autograft, often using sensitive nerves from the patient's leg. However, this procedure is associated with donor site morbidity and with an increase in the likelihood of surgical complications. In addition, the availability of donor nerves is limited. To avoid these restrictions, synthetic nerve guidance conduits (NGCs) have been explored for many years. These NGCs bridge the nerve defect, and allow the orderly ingrowth of axons from the proximal to the distal stump of the severed nerve. So far, such NGCs can only ensure reliable functional results in smaller sensitive nerves (< 3 mm diameter, e.g. digital nerves) and short defect distances (< 30 mm). The aim of the present proposal is to fabricate an NGC, which shows at least equivalent results to an autograft at longer defect distances and also, when treating larger, mixed motor-sensitive nerves. The project is based on the recent finding that blood capillaries are the first structures to bridge the gap between the proximal and distal nerve endings. These are followed by Schwann cells, and finally by axons. We intend to use innovative 3D bioprinting technologies to fabricate an NGC that contains endothelial cell strands preformed in a hydrogel. As we have shown in previous experiments, such strands are able to form blood vessels in vivo, which connect to the blood circulation of the recipient. We postulate that these preformed endothelial strands will serve as guide rails for Schwann cells and subsequently for regenerating axons. In addition to endothelial cells and Schwann cells, the NGC will be surrounded by a solid outer sheath of degradable thermoplastic, that will enable microsurgical coaptation. We postulate that such a microvascularized NGC will be the basis for a new generation of NGCs for the treatment of defects in larger mixed motor-sensitive nerves and longer defect distances.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Günter Finkenzeller, until 12/2023 (†)