Displaying One Session

Potsdam 3 Morning Workshop
Session Type
Morning Workshop
Date
14.04.2022
Time
07:30 - 08:15
Room
Potsdam 3
CME Evaluation (becomes available 5 minutes after the end of the session)
Extended Abstract (for invited Faculty only) Meniscus

13.2.1 - All You Need to Know About Meniscus: Meniscus Discovery Series

Presentation Topic
Meniscus
Date
14.04.2022
Lecture Time
07:30 - 07:38
Room
Potsdam 3
Session Type
Morning Workshop
Extended Abstract (for invited Faculty only) Meniscus

13.2.2 - Meniscal Preservation Possible? Orthobiologics

Presentation Topic
Meniscus
Date
14.04.2022
Lecture Time
07:38 - 07:46
Room
Potsdam 3
Session Type
Morning Workshop
Extended Abstract (for invited Faculty only) Cartilage and Meniscus

13.2.3 - Meniscus: Future developments from a cellular and molecular perspective

Presentation Topic
Cartilage and Meniscus
Date
14.04.2022
Lecture Time
07:46 - 07:54
Room
Potsdam 3
Session Type
Morning Workshop

Abstract

Introduction

The meniscus plays an important role in knee function due to its roles in protecting the underlying articular cartilage from excessive high loads during motion and aiding in joint biomechanics and proprioception. It is composed of two distinct regions, an inner avascular region and an outer vascular region that has been extensively characterized in previous publications (1, 2). The avascular region has a matrix predominantly composed of collagen II and glycosaminoglycan similar to articular cartilage. In contrast, the vascular region is composed mainly of collagen I with vasculature throughout the outer half of the meniscus. Additionally, neurons are found at the horns of the meniscus that attach the tissue to the underlying bone (1, 2, 3). This unique structure is due to the loading mechanics during meniscus development, whereby the inner region is under compressive loading, whilst the outer region undergoes tensile loading, thus resulting in a heterogeneous tissue composition (3). However, inspite of this knowledge, the developmental, cellular and molecular aspects of the meniscus remain poorly understood compared to other musculoskeletal tissues (i.e. articular cartilage or bone). A greater understanding in the developmental and cellular aspects of the meniscus would help to form the basis of novel cell therapies and pharmacological strategies for meniscus treatment that preserve the tissue and prevent the onset of early osteoarthritis (4).

Content

This presentation will provide an overview of the current understanding of meniscus development and cellular function. Recent studies investigating joint development in mouse models have demonstrated that the meniscus derives from interzone cells during mesenchymal development and that hedgehog signaling is one pathway controlling its embryogenesis (5). We and other groups have begun to investigate meniscus-specific genes via microarray analysis, as previous studies have used a combination of cartilage and tendon specific genes to identify the meniscus phenotype. Identification of meniscus-specific genes could lead to the creation of meniscus induction protocols that can be applied to meniscus cells or to differentiate stem cells (e.g. bone marrow mesenchymal stem cells, embryonic, iPS) from different sources towards a meniscogenic lineage. We have also begun to study the presence of progenitor populations within both meniscus regions with the primary purpose of developing cell-based therapies (6). In parallel, we and other groups have begun to use different environmental conditions (e.g. oxygen tension, mechanical loading) to understand the optimal parameters for producing functional meniscus tissue (6). Our recent study has combined these approaches, whereby we have isolated a meniscus progenitor population that selectively adhered to fibronectin from both the avascular and vascular regions under a low oxygen tension or physioxia (6). Recent studies have used RNAseq to identify differential pathways between healthy and degenerative meniscus tissue that can be used for the establishment of pharmacological therapies and gain a greater understanding on meniscus development and degeneration (7). In summary, these recent publications show that the cellular and molecular aspects of the meniscus are critical in the design of novel therapeutic strategies that could lead a significant improvement in the quality of the life for the patient and prevent the onset of early osteoarthritis.

References

1) Verdonk PC, Forsyth RG, Wang J, Almqvist KF, Verdonk R, Veys EM, Verbruggen G: Characterisation of human knee meniscus cell phenotype. Osteoarthritis Cartilage. (2005) Jul;13(7):548-60.

2) Makris EA, Hadidi P, Athanasiou KA: The knee meniscus: structure-function, pathophysiology, current repair techniques, and prospects for regeneration. Biomaterials. (2011) Oct;32(30):7411-31.

3) Gray JC: Neural and vascular anatomy of the menisci of the human knee. J Orthop Sports Phys Ther. (1999) Jan;29(1):23-30.

4) Verdonk R, Madry H, Shabshin N, Dirisamer F, Peretti GM, Pujol N, Spalding T, Verdonk P, Seil R, Condello V, Di Matteo B, Zellner J, Angele P: The role of meniscal tissue in joint protection in early osteoarthritis. Knee Surg Sports Traumatol Arthrosc. (2016) Jun;24(6):1763-74.

5) Wei Y, Sun H, Gui T, Yao L, Zhong L, Yu W, Heo SJ, Han L, Dyment NA, Liu XS, Zhang Y, Koyama E, Long F, Zgonis MH, Mauck RL, Ahn J, Qin L: The critical role of Hedgehog-responsive mesenchymal progenitors in meniscus development and injury repair. Elife. (2021) Jun 4;10:e62917.

6) Pattappa G, Reischl F, Jahns J, Schewior R, Lang S, Zellner J, Johnstone B, Docheva D, Angele P: Fibronectin Adherent Cell Populations Derived From Avascular and Vascular Regions of the Meniscus Have Enhanced Clonogenicity and Differentiation Potential Under Physioxia. Front Bioeng Biotechnol. (2022) Jan 28;9:789621.

7) Sun H, Wen X, Li H, Wu P, Gu M, Zhao X, Zhang Z, Hu S, Mao G, Ma R, Liao W, Zhang Z: Single-cell RNA-seq analysis identifies meniscus progenitors and reveals the progression of meniscus degeneration. Ann Rheum Dis. (2020) Mar;79(3):408-417

Acknowledgments

The authors wish to acknowledge the funding support from European Union Horizon 2020 research and innovation programme (EU No.: 814444 (MEFISTO).

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Extended Abstract (for invited Faculty only) Biomaterials and Scaffolds

13.2.4 - New Technologies for Meniscal Regeneration: The Mefisto Approach

Presentation Topic
Biomaterials and Scaffolds
Date
14.04.2022
Lecture Time
07:54 - 08:02
Room
Potsdam 3
Session Type
Morning Workshop

Abstract

Introduction

Treating meniscal lesions remains a major challenge in the preservation of joint health and function. The relevance of addressing meniscal injuries and degeneration is especially important, since meniscectomy remains the preferred surgical approach to date. However, in recent decades, the evolving understanding of meniscal function lead many clinicins towards stategies to prever menisci whenever possible. In fact, the meniscus-deficient knee has been associated with poor outcomes over time, including deterioration of the articular cartilage and compromised stability of the joint, with progression towards a post-meniscectomy osteoarthritis (OA). The MEFISTO project is a European consortium composed of 13 institutions between academic hospitals, universities, and healthcare industry partners that is studying a new, personalized approach, in which a regenerative meniscal scaffold is developed to promote meniscal regeneration in young patient, and a bioactive, non-degradable prosthesis able to modulate joint inflammation is developed for patients with advanced OA. In this presentation, the key 3D printing technologies and approaches to biofunctionalize both the regenerative and non-degradable meniscal analogues that are designed and developed within the consortium will be discussed.

Content

In particular, 3D (bio)printing techniques are rapidly evolving as a powerful tool to capture the anatomical geometries of native tissues, as well as their heterocellular composition, via the spatial patterning of different ECM components, cells and bioactive cues. In the field of meniscus repair, this family of techniques, especially extrusion-based bioprinting can be particularly advantageous to recreate the zonal distribution into a vascular and an avascular zone, as well as the spatially defined integration of key anti- and pro-angiogenic factors to modulate the distribution of ingrowing blood capillaries. The technological innovation promoted by the MEFISTO consortium lies int he development of biologically active functionalized micro- and nanobiomaterials (specificall, including dendrons and drug delivery from polymeric capsules) that can interact with the surrounding articular tissues. In particular, the biodegradable scaffold witll promote the vascularization of the peripheral zone, while leaving th inner zone avascular, relecting the native meniscal tissue. Contextually, the functionalization with drug delivery particles within the surface of the non-degradable device will provide modulation of inflammation. In addition, the ability to print mechanically reinforcing materials, also in the form of microfibrillar polymeric meshes, i.e. via melt electrowriting, can be exploited to endow soft materials such a hydrogels and collagen sponges with mechanical properties analogue to those of native menisci. Finally, new light-based 3D volumetric (bio)printing technologies offer the opportunity to print cell laden structures of anatomically relevant sizes (several centimeters) at an unprecedented velocity, in less than 20 seconds, opening new avenues to facilitate the upscaling of tissue engineered constructs and their translation to meniscal healthcare. Overall, the combination of these 3D bioprinting technologies and the generation of drug loaded scaffolds and regenerative grafts, can offer new opportunities for joint restorative solutions.

Acknowledgments

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 814444 (MEFISTO) and from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 949806, VOLUME-BIO).

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