J. Malda (Utrecht, NL)

University Medical Center Utrecht Orthopaedics
Jos Malda is professor of Biofabrication in Translation Regenerative Medicine and Head of Research at the Department of Orthopaedics; University Medical Center Utrecht. He also has an appointment at the Department of Equine Sciences; University of Utrecht. He received his MSc degree in Bioprocess Engineering from Wageningen University in 1999 and completed my PhD on Cartilage Tissue Engineering in 2003 (University of Twente). In 2007; Dr Malda was awarded a fellowship that allowed him to establish his research group in Utrecht; which focuses on biofabrication and biomaterials design; in particular for the regeneration of (osteo)chondral defects. He has published over 140 articles in peer-reviewed international journals and attracted over 7 million Euro in research funding and holds an ERC Consolidator grant. He has beens a long-standing Board member of the International Cartilage Repair Society (ICRS) and the past President of the International Society for Biofabrication (ISBF).

Presenter Of 3 Presentations

Extended Abstract (for invited Faculty only) Biomaterials and Scaffolds

25.1.1 - Biomaterials & Hydrogels for Bioprinting of Cartilage

Presentation Topic
Biomaterials and Scaffolds
Date
15.04.2022
Lecture Time
12:30 - 12:45
Room
Potsdam 1
Session Type
Special Session
Poster Others

P033 - Microstructural Differences Between the Osteochondral Units of Terrestrial and Aquatic Mammals

Presentation Topic
Others
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

The osteochondral unit is the pivotal element of the mammalian joint, with a fundamental clinical relevance. It is known that in terrestrial mammals, that the biochemical components of the tissues of the osteochondral unit are strongly preserved across a wide range of species. There is, however, very limited knowledge of specific adaptations of the architecture of the cartilage extracellular matrix in aquatic mammals.

The aim of this study was, therefore, to investigate if and how the structure of both the cartilage and the bone component of the osteochondral unit differs between mammals living on land or in water.

Methods and Materials

To investigate this we analyzed the microstructural composition and architectural features of the osteochondral units from the humeral head of six aquatic and nine terrestrial mammalian species. Osteochondral tissue samples were harvested post-mortem from the weight bearing central area of the humeral head. Histological assesment was performed, and included saf-O staining and polarized light microscopy to visualize the orientation of the collagen fibers. The mechanical properties were assessed by uniaxial unconfined compression and Micro Computed Tomography (micro-CT) was performed.

Results

schermafbeelding 2021-10-14 om 18.00.22.png

Aquatic mammals feature cartilage with essentially random collagen fiber configuration, lacking the depth-dependent, arcade-like organization characteristic of terrestrial mammalian species. They have a less stiff articular cartilage at equilibrium with a significantly lower peak modulus, and at the osteochondral interface do not have a calcified cartilage layer, displaying only a thin, highly porous subchondral bone plate. Moreover, patches of cartilage tissue are present throughout the subchondral bone.

Conclusion

This totally different constitution of the osteochondral unit in aquatic mammals reflects that accommodation of loading is the primordial function of the osteochondral unit. Recognizing the crucial importance of this microarchitecture-function relationship is pivotal for the development of durable functional regenerative approaches for treatment of joint damage.

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Poster Biomaterials and Scaffolds

P042 - Covalent Protein Immobilization on Melt Electrowritten Microfiber Scaffolds for Guided Cartilage Regeneration

Presentation Topic
Biomaterials and Scaffolds
Date
13.04.2022
Lecture Time
09:30 - 09:30
Room
Exhibition Foyer
Session Name
7.3 - Poster Viewing / Coffee Break / Exhibition
Session Type
Poster Session
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Current tissue engineering treatments for end-stage articular cartilage fail to produce long-term functional cartilage tissue. Here, melt electrowriting (MEW) is used to fabricate 3D scaffolds with micro-resolution to mimic the properties of the native cartilage extracellular matrix (Castilho et al., 2019). These scaffolds are activated using atmospheric-pressure plasma jet (APPJ), allowing for covalent immobilization of transforming growth factor β1 (TGF), an important cytokine for the production and maintenance of cartilage (Wang, Rigueur & Lyons, 2014), onto the scaffold’s microfibers. It is hypothesized these biofunctionalized scaffolds will support differentiation of mesenchymal stromal cells (MSCs) into the chondrogenic lineage and subsequent neo-cartilage formation.

Methods and Materials

Poly-e-caprolactone MEW scaffolds were fabricated using a 3DDiscovery printer (regenHU), then activated using a computer-controlled APPJ device (Alavi et al., 2020). TGF was subsequently immobilized onto the MEW scaffolds using solution submersion (1µg/mL). Characterization of protein immobilization was performed using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence detection. In vitro experiments were performed by seeding equine MSCs into the scaffolds and were cultured for 28 days. Neo-cartilage formation was quantified with dimethyl methylene blue/picogreen assays for glycosaminoglycan (GAG) production and confirmed with histological analysis.

Results

ELISA results confirmed covalent TGF concentration on the biofunctionalized scaffolds while immunofluorescently-labelled TGF was detected visually in scaffolds. The APPJ treatment caused increased hydrophilicity of the scaffolds, resulting in efficient cellular infiltration. In vitro analysis demonstrated that GAG production was significantly enhanced in both the immobilized TGF (+APPJ+TGF) and TGF (-APPJ+TGF) in medium groups, compared to the control groups without TGF supplementation (-APPJ+/-TGF). This finding was further validated by the heightened production of GAGs and collagen type II, observed in histological sections.

figure 1.jpg

Conclusion

We have demonstrated that APPJ-facilitated covalent immobilization of TGF retains bioactivity and stimulates differentiation of MSCs into the chondrogenic lineage. Our results also demonstrate that the new constructs with immobilized TGF support neo-cartilage formation.

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Moderator Of 2 Sessions

Potsdam 1 Plenary Session
Session Type
Plenary Session
Date
13.04.2022
Time
08:30 - 09:30
Room
Potsdam 1
Session Description
Digitalisation is a pandemic process and we are already in the mid of it. Propelled through the COVID19 pandemic the medical and scientific community has to cope with the benefits and downside of global development, various aspects of that phenomenon will be presented.
Session Learning Objective
  1. Participants should understand the mechanism and effects of digitalization and also critically analyze the advantages and problems of this global process - from artificial intelligence to fake news on the net.
CME Evaluation (becomes available 5 minutes after the end of the session)
Potsdam 3 Free Papers
Session Type
Free Papers
Date
14.04.2022
Time
11:15 - 12:45
Room
Potsdam 3
CME Evaluation (becomes available 5 minutes after the end of the session)

Presenter Of 2 Presentations

Others

P033 - Microstructural Differences Between the Osteochondral Units of Terrestrial and Aquatic Mammals

Abstract

Purpose

The osteochondral unit is the pivotal element of the mammalian joint, with a fundamental clinical relevance. It is known that in terrestrial mammals, that the biochemical components of the tissues of the osteochondral unit are strongly preserved across a wide range of species. There is, however, very limited knowledge of specific adaptations of the architecture of the cartilage extracellular matrix in aquatic mammals.

The aim of this study was, therefore, to investigate if and how the structure of both the cartilage and the bone component of the osteochondral unit differs between mammals living on land or in water.

Methods and Materials

To investigate this we analyzed the microstructural composition and architectural features of the osteochondral units from the humeral head of six aquatic and nine terrestrial mammalian species. Osteochondral tissue samples were harvested post-mortem from the weight bearing central area of the humeral head. Histological assesment was performed, and included saf-O staining and polarized light microscopy to visualize the orientation of the collagen fibers. The mechanical properties were assessed by uniaxial unconfined compression and Micro Computed Tomography (micro-CT) was performed.

Results

schermafbeelding 2021-10-14 om 18.00.22.png

Aquatic mammals feature cartilage with essentially random collagen fiber configuration, lacking the depth-dependent, arcade-like organization characteristic of terrestrial mammalian species. They have a less stiff articular cartilage at equilibrium with a significantly lower peak modulus, and at the osteochondral interface do not have a calcified cartilage layer, displaying only a thin, highly porous subchondral bone plate. Moreover, patches of cartilage tissue are present throughout the subchondral bone.

Conclusion

This totally different constitution of the osteochondral unit in aquatic mammals reflects that accommodation of loading is the primordial function of the osteochondral unit. Recognizing the crucial importance of this microarchitecture-function relationship is pivotal for the development of durable functional regenerative approaches for treatment of joint damage.

Collapse
Biomaterials and Scaffolds

P042 - Covalent Protein Immobilization on Melt Electrowritten Microfiber Scaffolds for Guided Cartilage Regeneration

Abstract

Purpose

Current tissue engineering treatments for end-stage articular cartilage fail to produce long-term functional cartilage tissue. Here, melt electrowriting (MEW) is used to fabricate 3D scaffolds with micro-resolution to mimic the properties of the native cartilage extracellular matrix (Castilho et al., 2019). These scaffolds are activated using atmospheric-pressure plasma jet (APPJ), allowing for covalent immobilization of transforming growth factor β1 (TGF), an important cytokine for the production and maintenance of cartilage (Wang, Rigueur & Lyons, 2014), onto the scaffold’s microfibers. It is hypothesized these biofunctionalized scaffolds will support differentiation of mesenchymal stromal cells (MSCs) into the chondrogenic lineage and subsequent neo-cartilage formation.

Methods and Materials

Poly-e-caprolactone MEW scaffolds were fabricated using a 3DDiscovery printer (regenHU), then activated using a computer-controlled APPJ device (Alavi et al., 2020). TGF was subsequently immobilized onto the MEW scaffolds using solution submersion (1µg/mL). Characterization of protein immobilization was performed using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence detection. In vitro experiments were performed by seeding equine MSCs into the scaffolds and were cultured for 28 days. Neo-cartilage formation was quantified with dimethyl methylene blue/picogreen assays for glycosaminoglycan (GAG) production and confirmed with histological analysis.

Results

ELISA results confirmed covalent TGF concentration on the biofunctionalized scaffolds while immunofluorescently-labelled TGF was detected visually in scaffolds. The APPJ treatment caused increased hydrophilicity of the scaffolds, resulting in efficient cellular infiltration. In vitro analysis demonstrated that GAG production was significantly enhanced in both the immobilized TGF (+APPJ+TGF) and TGF (-APPJ+TGF) in medium groups, compared to the control groups without TGF supplementation (-APPJ+/-TGF). This finding was further validated by the heightened production of GAGs and collagen type II, observed in histological sections.

figure 1.jpg

Conclusion

We have demonstrated that APPJ-facilitated covalent immobilization of TGF retains bioactivity and stimulates differentiation of MSCs into the chondrogenic lineage. Our results also demonstrate that the new constructs with immobilized TGF support neo-cartilage formation.

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