Strain-induced bands of Büngner formation promotes axon growth in 3D tissue-engineered constructs.

Treatment of peripheral nerve lesions remains a major challenge due to poor functional recovery; hence, ongoing research efforts strive to enhance peripheral nerve repair. In this study, we aimed to establish three-dimensional tissue-engineered bands of Büngner constructs by subjecting Schwann cells (SCs) embedded in fibrin hydrogels to mechanical stimulation. We show for the first time that the application of strain induces (i) longitudinal alignment of SCs resembling bands of Büngner, and (ii) the expression of a pronounced repair SC phenotype as evidenced by upregulation of BDNF, NGF, and p75NTR. Furthermore, we show that mechanically aligned SCs provide physical guidance for migrating axons over several millimeters in vitro in a co-culture model with rat dorsal root ganglion explants. Consequently, these constructs hold great therapeutic potential for transplantation into patients and might also provide a physiologically relevant in vitro peripheral nerve model for drug screening or investigation of pathologic or regenerative processes.

A systematic review and meta-analysis of studies comparing muscle-in-vein conduits with autologous nerve grafts for nerve reconstruction.

The gold-standard method for reconstruction of segmental nerve defects, the autologous nerve graft, has several drawbacks in terms of tissue availability and donor site morbidity. Therefore, feasible alternatives to autologous nerve grafts are sought. Muscle-in-vein conduits have been proposed as an alternative to autologous nerve grafts almost three decades ago, given the abundance of both tissues throughout the body. Based on the anti-inflammatory effects of veins and the proregenerative environment established by muscle tissue, this approach has been studied in various preclinical and some clinical trials. There is still no comprehensive systematic summary to conclude efficacy and feasibility of muscle-in-vein conduits for reconstruction of segmental nerve defects. Given this lack of a conclusive summary, we performed a meta-analysis to evaluate the potential of muscle-in-vein conduits. This work's main findings are profound discrepancies regarding the results following nerve repair by means of muscle-in-vein conduits in a preclinical or clinical setting. We identified differences in study methodology, inter-species neurobiology and the limited number of clinical studies to be the main reasons for the still inconclusive results. In conclusion, we advise for large animal studies to elucidate the feasibility of muscle-in-vein conduits for repair of segmental defects of critical size in mixed nerves.