Modular Bioreactor Design for Directed Tendon/Ligament Tissue Engineering

Functional tissue-engineered tendons and ligaments remain to be prepared in a reproducible and scalable manner. This study evaluates an acellular 3D extracellular matrix (ECM) scaffold for tendon/ligament tissue engineering and their ability to support strain-induced gene regulation associated with...

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Main Authors: Axel J. Delakowski, Jared D. Posselt, Christopher T. Wagner
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Bioengineering
Subjects:
Online Access:https://www.mdpi.com/2306-5354/9/3/127
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author Axel J. Delakowski
Jared D. Posselt
Christopher T. Wagner
author_facet Axel J. Delakowski
Jared D. Posselt
Christopher T. Wagner
author_sort Axel J. Delakowski
collection DOAJ
description Functional tissue-engineered tendons and ligaments remain to be prepared in a reproducible and scalable manner. This study evaluates an acellular 3D extracellular matrix (ECM) scaffold for tendon/ligament tissue engineering and their ability to support strain-induced gene regulation associated with the tenogenesis of cultured mesenchymal stromal cells. Preliminary data demonstrate unique gene regulation patterns compared to other scaffold forms, in particular in Wnt signaling. However, the need for a robust bioreactor system that minimizes process variation was also evident. A design control process was used to design and verify the functionality of a novel bioreactor. The system accommodates 3D scaffolds with clinically-relevant sizes, is capable of long-term culture with customizable mechanical strain regimens, incorporates in-line load measurement for continuous monitoring and feedback control, and allows a variety of scaffold configurations through a unique modular grip system. All critical functional specifications were met, including verification of physiological strain levels from 1–10%, frequency levels from 0.2–0.5 Hz, and accurate load measurement up to 50 N, which can be expanded on the basis of load cell capability. The design process serves as a model for establishing statistical functionality and reliability of investigative systems. This work sets the stage for detailed analyses of ECM scaffolds to identify critical differentiation signaling responses and essential matrix composition and cell–matrix interactions.
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spelling doaj.art-4ef4ecc3208b4760a5fbcf699c7d9f062023-11-24T00:30:29ZengMDPI AGBioengineering2306-53542022-03-019312710.3390/bioengineering9030127Modular Bioreactor Design for Directed Tendon/Ligament Tissue EngineeringAxel J. Delakowski0Jared D. Posselt1Christopher T. Wagner2Department of Biomedical Engineering, The College of New Jersey, Ewing, NJ 08628, USADepartment of Biomedical Engineering, The College of New Jersey, Ewing, NJ 08628, USADepartment of Biomedical Engineering, The College of New Jersey, Ewing, NJ 08628, USAFunctional tissue-engineered tendons and ligaments remain to be prepared in a reproducible and scalable manner. This study evaluates an acellular 3D extracellular matrix (ECM) scaffold for tendon/ligament tissue engineering and their ability to support strain-induced gene regulation associated with the tenogenesis of cultured mesenchymal stromal cells. Preliminary data demonstrate unique gene regulation patterns compared to other scaffold forms, in particular in Wnt signaling. However, the need for a robust bioreactor system that minimizes process variation was also evident. A design control process was used to design and verify the functionality of a novel bioreactor. The system accommodates 3D scaffolds with clinically-relevant sizes, is capable of long-term culture with customizable mechanical strain regimens, incorporates in-line load measurement for continuous monitoring and feedback control, and allows a variety of scaffold configurations through a unique modular grip system. All critical functional specifications were met, including verification of physiological strain levels from 1–10%, frequency levels from 0.2–0.5 Hz, and accurate load measurement up to 50 N, which can be expanded on the basis of load cell capability. The design process serves as a model for establishing statistical functionality and reliability of investigative systems. This work sets the stage for detailed analyses of ECM scaffolds to identify critical differentiation signaling responses and essential matrix composition and cell–matrix interactions.https://www.mdpi.com/2306-5354/9/3/127tendonligamentmesenchymal cellsdifferentiationextracellular matrixbioreactor
spellingShingle Axel J. Delakowski
Jared D. Posselt
Christopher T. Wagner
Modular Bioreactor Design for Directed Tendon/Ligament Tissue Engineering
Bioengineering
tendon
ligament
mesenchymal cells
differentiation
extracellular matrix
bioreactor
title Modular Bioreactor Design for Directed Tendon/Ligament Tissue Engineering
title_full Modular Bioreactor Design for Directed Tendon/Ligament Tissue Engineering
title_fullStr Modular Bioreactor Design for Directed Tendon/Ligament Tissue Engineering
title_full_unstemmed Modular Bioreactor Design for Directed Tendon/Ligament Tissue Engineering
title_short Modular Bioreactor Design for Directed Tendon/Ligament Tissue Engineering
title_sort modular bioreactor design for directed tendon ligament tissue engineering
topic tendon
ligament
mesenchymal cells
differentiation
extracellular matrix
bioreactor
url https://www.mdpi.com/2306-5354/9/3/127
work_keys_str_mv AT axeljdelakowski modularbioreactordesignfordirectedtendonligamenttissueengineering
AT jareddposselt modularbioreactordesignfordirectedtendonligamenttissueengineering
AT christophertwagner modularbioreactordesignfordirectedtendonligamenttissueengineering