A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement

Janne Spierings; Wietske Velthuijs; Amal Mansoor; Manon E. Bertrand; Jorge Alfredo Uquillas; Keita Ito; Rob P.A. Janssen; Jasper Foolen

doi:10.1186/s40634-022-00555-y

A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement

Janne Spierings
, Wietske Velthuijs
, Amal Mansoor
, Manon E. Bertrand
, Jorge Alfredo Uquillas
, Keita Ito
, Rob P.A. Janssen
, Jasper Foolen (Corresponding author)

Research output: Contribution to journal › Article › Academic › peer-review

14 Citations (Scopus)

205 Downloads (Pure)

Abstract

PURPOSE: Meniscus tears are one of the most frequent orthopedic knee injuries, which are currently often treated performing meniscectomy. Clinical concerns comprise progressive degeneration of the meniscus tissue, a change in knee biomechanics, and an early onset of osteoarthritis. To overcome these problems, meniscal transplant surgery can be performed. However, adequate meniscal replacements remain to be a great challenge. In this research, we propose the use of a decellularized and sterilized human meniscus allograft as meniscal replacement.

METHODS: Human menisci were subjected to a decellularization protocol combined with sterilization using supercritical carbon dioxide (scCO 2). The decellularization efficiency of human meniscus tissue was evaluated via DNA quantification and Hematoxylin & Eosin (H&E) and DAPI staining. The mechanical properties of native, decellularized, and decellularized + sterilized meniscus tissue were evaluated, and its composition was determined via collagen and glycosaminoglycan (GAG) quantification, and a collagen and GAG stain. Additionally, cytocompatibility was determined in vitro.

RESULTS: Human menisci were decellularized to DNA levels of ~ 20 ng/mg of tissue dry weight. The mechanical properties and composition of human meniscus were not significantly affected by decellularization and sterilization. Histologically, the decellularized and sterilized meniscus tissue had maintained its collagen and glycosaminoglycan structure and distribution. Besides, the processed tissues were not cytotoxic to seeded human dermal fibroblasts in vitro.

CONCLUSIONS: Human meniscus tissue was successfully decellularized, while maintaining biomechanical, structural, and compositional properties, without signs of in vitro cytotoxicity. The ease at which human meniscus tissue can be efficiently decellularized, while maintaining its native properties, paves the way towards clinical use.

Original language	English
Article number	116
Number of pages	11
Journal	Journal of Experimental Orthopaedics
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/s40634-022-00555-y
Publication status	Published - 5 Dec 2022

Funding

The authors acknowledge Antonio van der Lande for help in the tissue dissection. We have much appreciation and respect for the people who donate their bodies for this scientific project. The human bodies at the Department of Anatomy of the Radboud University Medical Center (Department of Medical Imaging, Anatomy, Radboud UMC, Nijmegen, The Netherlands) were obtained through the Dutch body donation program for science and education (Wet op de lijkbezorging, Art. 18 §1, Art. 19, Art. 67-70, April 1991, www.wetten.overheid.nl/BWBR0005009). At the Radboud UMC, body donations of humans aged 18 years and older with a valid handwritten statement were accepted. Human bodies were transported to the department of Anatomy within 24 h after death. Permission for dissection was requested from the mayor of the municipality where the donor died. After permission was given, the human body was fresh-frozen at -20 degrees Celsius within 72 hours after death. After dissection, human remains were transported back to the Department of Anatomy (Department of Medical Imaging, Anatomy, Radboud UMC, Nijmegen, The Netherlands) for anonymous cremation. JS and JF acknowledge the financial support of the European Union’s Horizon 2020 research and innovation programme under grant agreement No 952981. This publication is part of the project “ultrACLean”: A novel decellularized off-the-shelf human graft for improved anterior cruciate ligament reconstruction (with project number 17734) of the research programme Demonstrator which is (partly) financed by the Dutch Research Council (NWO).

Funders	Funder number
European Union's Horizon 2020 - Research and Innovation Framework Programme	952981, 17734
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

Allograft
Decellularization
Meniscal reconstruction
Meniscus
Supercritical carbon dioxide sterilization

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10.1186/s40634-022-00555-y

pdfFinal published version, 2.04 MBLicence: CC BY

Cite this

@article{74afe65a8dd14a3a900492482a084ca4,

title = "A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement",

abstract = "PURPOSE: Meniscus tears are one of the most frequent orthopedic knee injuries, which are currently often treated performing meniscectomy. Clinical concerns comprise progressive degeneration of the meniscus tissue, a change in knee biomechanics, and an early onset of osteoarthritis. To overcome these problems, meniscal transplant surgery can be performed. However, adequate meniscal replacements remain to be a great challenge. In this research, we propose the use of a decellularized and sterilized human meniscus allograft as meniscal replacement.METHODS: Human menisci were subjected to a decellularization protocol combined with sterilization using supercritical carbon dioxide (scCO 2). The decellularization efficiency of human meniscus tissue was evaluated via DNA quantification and Hematoxylin \& Eosin (H\&E) and DAPI staining. The mechanical properties of native, decellularized, and decellularized + sterilized meniscus tissue were evaluated, and its composition was determined via collagen and glycosaminoglycan (GAG) quantification, and a collagen and GAG stain. Additionally, cytocompatibility was determined in vitro. RESULTS: Human menisci were decellularized to DNA levels of \textasciitilde{} 20 ng/mg of tissue dry weight. The mechanical properties and composition of human meniscus were not significantly affected by decellularization and sterilization. Histologically, the decellularized and sterilized meniscus tissue had maintained its collagen and glycosaminoglycan structure and distribution. Besides, the processed tissues were not cytotoxic to seeded human dermal fibroblasts in vitro.CONCLUSIONS: Human meniscus tissue was successfully decellularized, while maintaining biomechanical, structural, and compositional properties, without signs of in vitro cytotoxicity. The ease at which human meniscus tissue can be efficiently decellularized, while maintaining its native properties, paves the way towards clinical use.",

keywords = "Allograft, Decellularization, Meniscal reconstruction, Meniscus, Supercritical carbon dioxide sterilization",

author = "Janne Spierings and Wietske Velthuijs and Amal Mansoor and Bertrand, \{Manon E.\} and Uquillas, \{Jorge Alfredo\} and Keita Ito and Janssen, \{Rob P.A.\} and Jasper Foolen",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = dec,

day = "5",

doi = "10.1186/s40634-022-00555-y",

language = "English",

volume = "9",

journal = "Journal of Experimental Orthopaedics",

issn = "2197-1153",

publisher = "Springer Open",

number = "1",

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TY - JOUR

T1 - A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement

AU - Spierings, Janne

AU - Velthuijs, Wietske

AU - Mansoor, Amal

AU - Bertrand, Manon E.

AU - Uquillas, Jorge Alfredo

AU - Ito, Keita

AU - Janssen, Rob P.A.

AU - Foolen, Jasper

PY - 2022/12/5

Y1 - 2022/12/5

N2 - PURPOSE: Meniscus tears are one of the most frequent orthopedic knee injuries, which are currently often treated performing meniscectomy. Clinical concerns comprise progressive degeneration of the meniscus tissue, a change in knee biomechanics, and an early onset of osteoarthritis. To overcome these problems, meniscal transplant surgery can be performed. However, adequate meniscal replacements remain to be a great challenge. In this research, we propose the use of a decellularized and sterilized human meniscus allograft as meniscal replacement.METHODS: Human menisci were subjected to a decellularization protocol combined with sterilization using supercritical carbon dioxide (scCO 2). The decellularization efficiency of human meniscus tissue was evaluated via DNA quantification and Hematoxylin & Eosin (H&E) and DAPI staining. The mechanical properties of native, decellularized, and decellularized + sterilized meniscus tissue were evaluated, and its composition was determined via collagen and glycosaminoglycan (GAG) quantification, and a collagen and GAG stain. Additionally, cytocompatibility was determined in vitro. RESULTS: Human menisci were decellularized to DNA levels of ~ 20 ng/mg of tissue dry weight. The mechanical properties and composition of human meniscus were not significantly affected by decellularization and sterilization. Histologically, the decellularized and sterilized meniscus tissue had maintained its collagen and glycosaminoglycan structure and distribution. Besides, the processed tissues were not cytotoxic to seeded human dermal fibroblasts in vitro.CONCLUSIONS: Human meniscus tissue was successfully decellularized, while maintaining biomechanical, structural, and compositional properties, without signs of in vitro cytotoxicity. The ease at which human meniscus tissue can be efficiently decellularized, while maintaining its native properties, paves the way towards clinical use.

AB - PURPOSE: Meniscus tears are one of the most frequent orthopedic knee injuries, which are currently often treated performing meniscectomy. Clinical concerns comprise progressive degeneration of the meniscus tissue, a change in knee biomechanics, and an early onset of osteoarthritis. To overcome these problems, meniscal transplant surgery can be performed. However, adequate meniscal replacements remain to be a great challenge. In this research, we propose the use of a decellularized and sterilized human meniscus allograft as meniscal replacement.METHODS: Human menisci were subjected to a decellularization protocol combined with sterilization using supercritical carbon dioxide (scCO 2). The decellularization efficiency of human meniscus tissue was evaluated via DNA quantification and Hematoxylin & Eosin (H&E) and DAPI staining. The mechanical properties of native, decellularized, and decellularized + sterilized meniscus tissue were evaluated, and its composition was determined via collagen and glycosaminoglycan (GAG) quantification, and a collagen and GAG stain. Additionally, cytocompatibility was determined in vitro. RESULTS: Human menisci were decellularized to DNA levels of ~ 20 ng/mg of tissue dry weight. The mechanical properties and composition of human meniscus were not significantly affected by decellularization and sterilization. Histologically, the decellularized and sterilized meniscus tissue had maintained its collagen and glycosaminoglycan structure and distribution. Besides, the processed tissues were not cytotoxic to seeded human dermal fibroblasts in vitro.CONCLUSIONS: Human meniscus tissue was successfully decellularized, while maintaining biomechanical, structural, and compositional properties, without signs of in vitro cytotoxicity. The ease at which human meniscus tissue can be efficiently decellularized, while maintaining its native properties, paves the way towards clinical use.

KW - Allograft

KW - Decellularization

KW - Meniscal reconstruction

KW - Meniscus

KW - Supercritical carbon dioxide sterilization

UR - https://www.scopus.com/pages/publications/85143376685

U2 - 10.1186/s40634-022-00555-y

DO - 10.1186/s40634-022-00555-y

M3 - Article

C2 - 36464727

SN - 2197-1153

VL - 9

JO - Journal of Experimental Orthopaedics

JF - Journal of Experimental Orthopaedics

IS - 1

M1 - 116

ER -

A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement

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Eindhoven University of Technology Researchers Broaden Understanding of Extracellular Matrix Proteins (A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement)

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A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement

Abstract

Funding

Keywords

Access to Document

Other files and links

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Eindhoven University of Technology Researchers Broaden Understanding of Extracellular Matrix Proteins (A decellularized and sterilized human meniscus allograft for off-the-shelf meniscus replacement)

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