Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (electrospun poly (l-lactic acid) [PLLA]) loaded with ibuprofen and triiodothyronine (T3) to counteract inflammation, thus improving endogenous regeneration. In vivo efficacy was tested by implanting the drug-loaded PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e., controls), the recovery stabilized at 21 days post-lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA + ibuprofen (Ibu) + T3 (PLLA-Ibu-T3) rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49 DPL. Glutamate release at 24 h and 8 DPL was reduced in PLLA-Ibu-T3-compared to PLLA-implanted rats, such as the estimated lesion volume at 60 DPL. The myelin-and 200-neurofilament-positive area fraction was higher in PLLA-Ibu-T3-implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with Ibu and T3 significantly improves the endogenous regeneration, leading to an improvement of functional locomotion outcome in the SCI.

Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System / Bighinati, A.; Focarete, M. L.; Gualandi, C.; Pannella, M.; Giuliani, A.; Beggiato, S.; Ferraro, L.; Lorenzini, L.; Giardino, L.; Calza, L.. - In: JOURNAL OF NEUROTRAUMA. - ISSN 0897-7151. - 37:15(2020), pp. 1708-1719. [10.1089/neu.2019.6949]

Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System

Bighinati A.;Gualandi C.;
2020

Abstract

Spinal cord injury (SCI) is an incurable condition, in which a cascade of cellular and molecular events triggered by inflammation and excitotoxicity impairs endogenous regeneration, namely remyelination and axonal outgrowth. We designed a treatment solution based on an implantable biomaterial (electrospun poly (l-lactic acid) [PLLA]) loaded with ibuprofen and triiodothyronine (T3) to counteract inflammation, thus improving endogenous regeneration. In vivo efficacy was tested by implanting the drug-loaded PLLA in the rat model of T8 contusion SCI. We observed the expected recovery of locomotion beginning on day 7. In PLLA-implanted rats (i.e., controls), the recovery stabilized at 21 days post-lesion (DPL), after which no further improvement was observed. On the contrary, in PLLA + ibuprofen (Ibu) + T3 (PLLA-Ibu-T3) rats a further recovery and a significant treatment effect were observed, also confirmed by the gait analysis on 49 DPL. Glutamate release at 24 h and 8 DPL was reduced in PLLA-Ibu-T3-compared to PLLA-implanted rats, such as the estimated lesion volume at 60 DPL. The myelin-and 200-neurofilament-positive area fraction was higher in PLLA-Ibu-T3-implanted rats, where the percentage of astrocytes was significantly reduced. The implant of a PLLA electrospun scaffold loaded with Ibu and T3 significantly improves the endogenous regeneration, leading to an improvement of functional locomotion outcome in the SCI.
2020
37
15
1708
1719
Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System / Bighinati, A.; Focarete, M. L.; Gualandi, C.; Pannella, M.; Giuliani, A.; Beggiato, S.; Ferraro, L.; Lorenzini, L.; Giardino, L.; Calza, L.. - In: JOURNAL OF NEUROTRAUMA. - ISSN 0897-7151. - 37:15(2020), pp. 1708-1719. [10.1089/neu.2019.6949]
Bighinati, A.; Focarete, M. L.; Gualandi, C.; Pannella, M.; Giuliani, A.; Beggiato, S.; Ferraro, L.; Lorenzini, L.; Giardino, L.; Calza, L.
File in questo prodotto:
File Dimensione Formato  
Improved Functional Recovery in Rat Spinal Cord Injury Induced by a Drug Combination Administered with an Implantable Polymeric Delivery System.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 1.72 MB
Formato Adobe PDF
1.72 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1318435
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 16
social impact