M. Karperien (Enschede, NL)

University of Twente Developmenal BioEngineering
Marcel Karperien studied biology at the University of Utrecht in the Netherlands. After a PhD in developmental biology in which he studied the molecular mechanisms underlying skeletal development; he worked 12 years at the Leiden University Medical Center on various aspects of endochondral ossification. In 2007 he moved to the University of Twente; to combine developmental biology of the skeleton with technology to improve strategies for cartilage regeneration. In 2012 he founded the department of Developmental BioEngineering (DBE) and became a full professor. The Department of Developmental BioEngineering (www.utwente.nl/tnw/dbe) is part of the MIRA institute for Biomedical Technology and Technical Medicine; which is ranked as the 7th best bioengineering institute worldwide. Currently the DBE group comprises 14 PhD students. Research focuses on i) developing injectable hydrogels for cartilage repair; ii) elucidating molecular mechanism underlying chondrocyte homeostasis; iii) improving cartilage formation; iv) the role of stem cells in cartilage regeneration; and v) exploring novel technologies for improved cartilage repair strategies. Prof. dr. Karperien is PI and participant in (inter)national projects focusing on cartilage repair including the Biomedical Materials Program; the Smartmix TeRM program; the National Initiative for Regenerative Medicine and projects funded by the Dutch Arthritis Association. More recently he started a 4mEuro National program fighting osteoarthritis by uniting 7 leading Dutch Academic groups in osteoarthritis research with 12 industrial partners co funded by the Dutch Arthritis Association and the Dutch government.

Presenter Of 1 Presentation

 ICRS 2022 - Online Programme
Podium Presentation Biomaterials and Scaffolds

16.2.10 - Antibody Fragments-Immobilized Injectable Hydrogels for Neutralizing Inflammatory and Pro-Catabolic Cytokines

Presentation Topic
Biomaterials and Scaffolds
Date
14.04.2022
Lecture Time
12:18 - 12:27
Room
Potsdam 3
Session Name
16.2 - Biomaterials & Bioprinting
Session Type
Free Papers
Speaker
Authors
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Intra-articular injection with biologicals like pro-catabolic cytokine neutralizing antibodies to treat osteoarthritis (OA) is challenging due to the short retention time of these biologicals in the joint space. To address this issue, we first attach the antibody fragments to polymer conjugates that can form an hydrogel by in situ cross linking upon injection in the intra-articular space. To test this concept we have employed the variable domain of heavy chain of single chain only antibody (VHHs) neutralizing TNFα for cytokine capture. The aim of this study is to provide a proof of this strategy aimed at creating a cytokine sink in the joint space.

Methods and Materials

In this study, we have selected a VHH that effectively neutralizes TNFα. Recombinant DNA technology was used to introduce an unpaired cysteine in the C-terminus of the VHH. Hyaluronic acid was functionalized with maleimide, needed for coupling of VHH, and tyramine residues, needed for hydrogel formation. Hydrogels functionalized with the VHH were prepared by mixing the hyaluronic acid-VHH-tyramine conjugates with the enzyme peroxidase and H2O2. Biological activity of the functionalized hydrogels was measured using an NFκb responsive luciferase reporter cell line after stimulation with TNFα.

Results

We show successful conjugation of the VHH to the polymer backbone via thiol-maleimide chemistry, while maintaining the binding affinity of the VHH against TNFα. The VHH functionalized polymer could be used for making stable hydrogels after tyramine mediated cross linking. Using an NF-κB luciferase reporter cell line we demonstrated that hydrogels functionalized with the VHH efficiently inactivated TNFα.

Conclusion

We successfully developed a biocompatible and efficient way to couple VHH to hyaluronic acid. These conjugates could be used for generation of cytokine sinks capable of capturing different pro-catabolic cytokines involved in OA after an intra-articular injection.

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Moderator Of 1 Session

 ICRS 2022 - Online Programme
Potsdam 1 Plenary Session

14.0 - Biological Matrices

Session Type
Plenary Session
Date
14.04.2022
Time
08:30 - 09:30
Room
Potsdam 1
Moderators
Session Description
Worldwide experts discuss the importance of using matrices and scaffolds adapted for clinical applications to enhance cartilage repair using cells and released factors.
Session Learning Objective
  1. Participants will be provided the latest information on the best suited biological materials and environment to improve cartilage repair.
CME Evaluation (becomes available 5 minutes after the end of the session)
Session Evaluation

Meeting Participant Of

 ICRS 2022 - Online Programme
Tegel Meeting Room (50) ICRS Committee Meeting

Registry Steering Committee Meeting

Session Type
ICRS Committee Meeting
Date
14.04.2022
Time
10:45 - 11:30
Room
Tegel Meeting Room (50)
Moderators
Meeting Participant