Validation of a new method for human nerve decellularization: toward a new tool in peripheral nerve reconstructive surgery.

Bolognesi, Federico (2023) Validation of a new method for human nerve decellularization: toward a new tool in peripheral nerve reconstructive surgery., [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze chirurgiche, 35 Ciclo. DOI 10.48676/unibo/amsdottorato/10660.
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Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. In case of peripheral nerve injury, the first approach is primary neurorrhaphy, which is direct nerve repair with epineural microsutures of the two stumps. However, this is not feasible in case of stump retraction or in case of tissue loss (gap > 2 cm), where the main surgical options are autologous grafts, allogenic grafts, or nerve conduits. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable donor site morbidity and functional deficit. Fresh nerve allografts have therefore become a viable alternative option, but they require immunosuppression, which is often contraindicated. Acellular Nerve Allografts (ANA) represent a valid alternative, they do not need immunosuppression and appear to be safe and effective based on recent studies. The purpose of this study is to propose and develop an innovative method of nerve decellularization (Rizzoli method), conforming to cleanroom requirements in order to perform the direct tissue manipulation step and the nerve decellularization process within five hours, so as to accelerate the detachment of myelin and cellular debris, without detrimental effects on nerve architecture. In this study, the safety and the efficacy of the new method are evaluated in vitro and in vivo by histological, immunohistochemical, and histomorphometric studies in rabbits and humans. The new method is rapid, safe, and cheaper if compared with available commercial ANAs. The present study shows that the method, previously optimized in vitro and in vivo on animal model presented by our group, can be applied on human nerve samples. This work represents the first step in providing a novel, safe, and inexpensive tool for use by European tissue banks to democratize the use of nerve tissue transplantation for nerve injury reconstruction.

Tipologia del documento
Tesi di dottorato
Bolognesi, Federico
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
allografting; decellularization; nerve regeneration; reconstructive surgery; tissue transplantation
Data di discussione
21 Marzo 2023

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