Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles

Jetze Visser; Debby Gawlitta; Kim E. M. Benders; Selynda M. H. Toma; Behdad Pouran; P. Rene van Weeren; Wouter J. A. Dhert; Jos Malda

doi:10.1016/j.biomaterials.2014.10.020

Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles

Jetze Visser, Debby Gawlitta, Kim E. M. Benders, Selynda M. H. Toma, Behdad Pouran, P. Rene van Weeren, Wouter J. A. Dhert, Jos Malda^*

^*Corresponding author for this work

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

Abstract

The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 +/- 2.5% vs. 39.5 +/- 8.3% (mean +/- standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. (C) 2014 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	174-182
Number of pages	9
Journal	Biomaterials
Volume	37
DOIs	https://doi.org/10.1016/j.biomaterials.2014.10.020
Publication status	Published - Jan 2015

Funding

The authors would like to thank Kristel Boere for her assistance with the mechanical testing and Mattie van Rijen for his assistance in fluorescent microscope imaging. The antibody against collagen type II (II-II6B3), developed by T.F Linsenmayer, was obtained from the DSHB developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242. Jetze Visser was supported by a grant from the Dutch Government to the Netherlands Institute for Regenerative Medicine (NIRM, grant no FES0908); DG was supported by a VENI Fellowship (11208) from the Dutch Technology Foundation, STW, Applied Science Division of NWO and the Technology Program of the Ministry of Economic Affairs. Kim Benders received an Alexandre Suerman Stipendium from the University Medical Center Utrecht and Jos Malda was supported by the Dutch Arthritis Foundation.

Keywords

Tissue engineering
Regeneration
Rat
Decellularized matrix
GelMA
MESENCHYMAL STEM-CELLS
TISSUE-ENGINEERED CONSTRUCTS
MULTIPOTENT STROMAL CELLS
EXTRACELLULAR-MATRIX
REGENERATIVE MEDICINE
OXYGEN-TENSION
GROWTH-PLATE
ADULT HUMAN
OSSIFICATION
CHONDROGENESIS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.biomaterials.2014.10.020

Cite this

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title = "Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles",

abstract = "The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 +/- 2.5% vs. 39.5 +/- 8.3% (mean +/- standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. (C) 2014 Elsevier Ltd. All rights reserved.",

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author = "Jetze Visser and Debby Gawlitta and Benders, {Kim E. M.} and Toma, {Selynda M. H.} and Behdad Pouran and {van Weeren}, {P. Rene} and Dhert, {Wouter J. A.} and Jos Malda",

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AU - Visser, Jetze

AU - Gawlitta, Debby

AU - Benders, Kim E. M.

AU - Toma, Selynda M. H.

AU - Pouran, Behdad

AU - van Weeren, P. Rene

AU - Dhert, Wouter J. A.

AU - Malda, Jos

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N2 - The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 +/- 2.5% vs. 39.5 +/- 8.3% (mean +/- standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. (C) 2014 Elsevier Ltd. All rights reserved.

AB - The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 +/- 2.5% vs. 39.5 +/- 8.3% (mean +/- standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. (C) 2014 Elsevier Ltd. All rights reserved.

KW - Tissue engineering

KW - Regeneration

KW - Rat

KW - Decellularized matrix

KW - GelMA

KW - MESENCHYMAL STEM-CELLS

KW - TISSUE-ENGINEERED CONSTRUCTS

KW - MULTIPOTENT STROMAL CELLS

KW - EXTRACELLULAR-MATRIX

KW - REGENERATIVE MEDICINE

KW - OXYGEN-TENSION

KW - GROWTH-PLATE

KW - ADULT HUMAN

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KW - CHONDROGENESIS

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DO - 10.1016/j.biomaterials.2014.10.020

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SN - 0142-9612

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SP - 174

EP - 182

JO - Biomaterials

JF - Biomaterials

ER -

Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles

Abstract

Funding

Keywords

UN SDGs

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