In Vitro Models for the Development of Peripheral Nerve Conduits, Part I: Design of a Fibrin Gel-Based Non-Contact Test.

Paola De Stefano,Angelica Silvia Federici,Lorenza Draghi

doi:10.3390/polym13203573

Paola De Stefano, Angelica Silvia Federici + Show 1 more

Open Access

https://doi.org/10.3390/polym13203573

Copy DOI

Abstract

Current clinical strategies to repair peripheral nerve injuries draw on different approaches depending on the extent of lost tissue. Nerve guidance conduits (NGCs) are considered to be a promising, off-the-shelf alternative to autografts when modest gaps need to be repaired. Unfortunately, to date, the implantation of an NGC prevents the sacrifice of a healthy nerve at the price of suboptimal clinical performance. Despite the significant number of materials and fabrication strategies proposed, an ideal combination has not been yet identified. Validation and comparison of NGCs ultimately requires in vivo animal testing due to the lack of alternative models, but in the spirit of the 3R principles, a reliable in vitro model for preliminary screening is highly desirable. Nevertheless, more traditional in vitro tests, and direct cell seeding on the material in particular, are not representative of the actual regeneration scenario. Thus, we have designed a very simple set-up in the attempt to appreciate the relevant features of NGCs through in vitro testing, and we have verified its applicability using electrospun NGCs. To this aim, neural cells were encapsulated in a loose fibrin gel and enclosed within the NGC membrane. Different thicknesses and porosity values of two popular polymers (namely gelatin and polycaprolactone) were compared. Results indicate that, with specific implementation, the system might represent a useful tool to characterize crucial NGC design aspects.

Highlights

They are considered significantly less often than central system lesions, peripheral nerve injuries affect millions of people every year [1,2,3], and most of them result in the severe impairment of motor and sensory functions [1,4]
Instead of seeding cells on the guide, neural cells were encapsulated in a loose fibrin gel and enclosed within the Nerve guidance conduits (NGCs) membrane
The initial value of 71% ± 14%, recorded for gelatin NGCs, dropped significantly to 21% ± 5% when value of 71% ± 14%, recorded for gelatin NGCs, dropped significantly to 21% ± 5% when

Summary

Introduction

They are considered significantly less often than central system lesions, peripheral nerve injuries affect millions of people every year [1,2,3], and most of them result in the severe impairment of motor and sensory functions [1,4]. Current therapeutic strategies involve a range of approaches according to the severity of the injury and the length of the gap. For gaps longer than 3 cm, autograft still represents the gold standard [6,7], but it has different shortcomings, such as donor site morbidity, limited supply, the sacrifice of a healthy nerve, and potential size discrepancies between the injured and the harvested nerve [4]. Nerve guidance conduits (NGC) represent a clinically available alternative in the case of modest gaps. They can overcome some of the limitations associated with autografts, such as availability, donor site morbidity, or size mismatches, but clinical results are still unsatisfactory [7,8]

Methods

Results

Conclusion