Abstract
Tissue engineering approaches in nerve regeneration often aim to improve results by bridging nerve defects with conduits that mimic key features of the nerve autograft. One such approach uses Schwann cell self-alignment and stabilization within collagen gels to generate engineered neural tissue (EngNT). In this study, we investigated whether a novel blend of fibrin and collagen could be used to form EngNT, as before EngNT design a beneficial effect of fibrin on Schwann cell proliferation was observed. A range of blend formulations was tested in terms of mechanical behavior (gel formation, stabilization, swelling, tensile strength, and stiffness), and lead formulations were assessed in vitro. A 90% collagen 10% fibrin blend was found to promote SCL4.1/F7 Schwann cell viability and supported the formation of aligned EngNT, which enhanced neurite outgrowth in vitro (NG108 cells) compared to formulations with higher and lower fibrin content. Initial in vivo tests in an 8 mm rat sciatic nerve model using rolled collagen-fibrin EngNT rods revealed a significantly enhanced axonal count in the midsection of the repair, as well as in the distal part of the nerve after 4 weeks. This optimized collagen-fibrin blend therefore provides a novel way to improve the capacity of EngNT to promote regeneration following peripheral nerve injury.
Highlights
Peripheral nerve injuries affect *300,000 people annually in Europe and are a major burden to patients and social and healthcare systems due to frequent hospitalization, pain, and resulting disabilities.[1]
Prolonged culture revealed a sustained effect of fibrin on Schwann cell proliferation, resulting in an increase of 43.2% compared with collagen and 51.0% compared with tissue culture polystyrene (TCPS)
The study presented focuses on improving engineered neural tissue (EngNT) technology, an approach developed for the construction of living artificial nerve tissue that mimics key features of the nerve graft and has previously been made using type I collagen
Summary
Peripheral nerve injuries affect *300,000 people annually in Europe and are a major burden to patients and social and healthcare systems due to frequent hospitalization, pain, and resulting disabilities.[1]. Transplantation of autologous nerve tissue is considered the current clinical gold standard; autografts are limited in availability and prone to unsatisfactory success rates, as well as side effects such as donor site morbidity.[1,2,3,4,5]. The use of artificial conduits, as well as decellularized allografts, to restore continuity between the proximal and distal stumps of a transected nerve has been the subject of a large number of investigations Some of these approaches are currently used in clinical nerve repair, there is an ongoing debate concerning their appropriate use, effectiveness, and side effects.[6,7] One of the reasons for the unsatisfactory outcome after repair of long-distance gaps is the limited proliferative capacity of Schwann cells.[8,9] Schwann cells play a key role in peripheral nerve regeneration as after injury they switch into a regenerative phenotype and proliferate to form the bands of Bungner, generating a highly aligned environment for the support and guidance of axons.[10,11]
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