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Development-of-an-engineered-tendon-enthesis-like

Sviluppo di uno scaffold ingegnerizzato iperelastico per la rigenerazione dell’entesi tendinea

Abstract

L’entesi tendine-osso (TTBE) è una struttura composta da tessuto connettivo specializzato, essenziale per garantire una transizione graduale tra tessuto tendineo ed osseo.

Gli infortuni che interessano il TTBE hanno un’elevata incidenza clinica soprattutto negli anziani e nelle popolazioni più attive che praticano sport a vari livelli.

Ogni anno nell’UE e negli USA circa 30 milioni di persone siano sottoposte a procedure di riparazione di tendini/legamenti, con una spesa annua di oltre 150 miliardi di euro. Nonostante le diverse tecniche innovative che sono state sviluppate, la riparazione chirurgica di lesioni da entesi massicce è ancora troppo spesso inadeguata, con un tasso di insuccesso che può arrivare al 79% nei casi più gravi.

Lo scopo di questo progetto è quello di produrre un materiale che possa migliorare gli outcomes della chirurgia riparativa delle TTBE. Per questo, abbiamo realizzato uno scaffold cellularizzato che imita il tessuto di transizione bifasico tendine-fibrocartilagineo del TTBE. Il costrutto è composto da un lato simile a un tendine e un lato simile alla cartilagine, cellularizzato con cellule staminali mesenchimali umane adulte (hMSC). Il nucleo strutturale del nostro costrutto è uno scaffold composto da poly(L-lactide-co-glicolide) di grado medico (PLGA), con elevata porosità interna e proprietà elastiche sufficienti a formare una rete autoportante, e in grado di supportare la proliferazione cellulare.

Impatto:
Con questo progetto abbiamo mirato a sviluppare un costrutto che mima l’entesi tendine-osso per soddisfare il bisogno clinico di costrutti ad alte prestazioni da utilizzare nella chirurgia ricostruttiva dei tendini. Il nostro costrutto ingegnerizzato ha promosso la differenziazione delle cellule staminali verso fenotipi cartilaginei e tendinei. A questo scopo abbiamo utilizzato un bioreattore innovativo che è parte del portfolio di proprietà intellettuale della Fondazione. Inoltre, le proprietà ad alta resistenza dello scaffold PLGA iperelastico conferiscono resistenza meccanica alla nostra struttura. Quindi, il nostro costrutto può supportare la riparazione chirurgica delle lesioni ai tendini, promuovendo una rapida guarigione e migliorando i risultati post-chirurgici.

Pipeline

  • CLINICAL
    NEED
  • DISEASES
    ANALYSIS
  • DISCOVERY
  • PRECLINICAL
    VALIDATION
  • PRECLINICAL
    DEVELOPMENT
  • CLINICAL
    STUDIES
Figura 1: H&E staining del costrutto bifasico (lato cartilagineo) dopo 7 giorni (A, B) e 21 giorni (C, D) di coltura a due diversi ingrandimenti. Le frecce nere indicano la matrice extracellulare di nuova produzione. Scale bar = 150 µm (A, C) e 50 µm (B, D). Contenuto di GAG dei costrutti espresso come rapporto GAG/DNA al giorno 21. I dati sono stati analizzati tramite unpaired t test con Welch correction, * p <0,05 (E). Espressione genica relativa di COL2A1 e TNMD al giorno 21 misurata mediante qRT-PCR (F,) normalizzata rispetto al controllo nello stesso time point. Calceina AM staining selettivo per le cellule vive eseguita sull'intero costrutto (G) e su una sezione longitudinale del costrutto (H) dopo 7 giorni di coltura in bioreattore.

Principal Investigator

Contatto

rgottardi@fondazionerimed.com

Aree terapeutiche:

Prodotto:
Dispositivi biomedicali e Organi artificiali

 

Collaborazioni:
University of Pennsylvania (UPenn), United States
Bioengineering and Biomaterials Laboratory, Children’s Hospital of Philadelphia (CHOP), United States
Center for Cellular and Molecular Engineering (CCME), University of Pittsburgh, United States
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, United States
Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, United States
The Chinese University of Hong Kong, China
Cell Biology Inspired Tissue Engineering, Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Netherlands
MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Netherlands

 

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ASME Journal of Engineering and Science in Medical Diagnostics and Therapy 2020, 3(3): 034501
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In-Vitro Hydrodynamic Assessment of a New Transcatheter Heart Valve Concept (The TRISKELE)
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Synthesis and in vitro evaluation of 5-substituted benzovesamicol analogs containing N-substituted amides as potential positron emission tomography tracers for the vesicular acetylcholine transporter
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Bioorganic & Medicinal Chemistry, 25: 5095–5106, 2017
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VASCULAR IMPLANT
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Book/Book Chapter
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Bioactive Nutraceuticals and Dietary Supplements in Neurological and Brain Disease: Prevention and Therapy
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Pledget-armed sutures affect the hemodynamic performance of biologic aortic valve substitutes: a preliminary experimental and computational study
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Elevated blood Hsp60, its structural similarities and cross-reactivity with thyroid molecules, and its presence on the plasma membrane of oncocytes point to the chaperonin as an immunopathogenic factor in Hashimoto's thyroiditis
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https://doi.org/
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