Displaying One Session

Bellevue Industry Satellite Symposium
Session Type
Industry Satellite Symposium
Date
13.04.2022
Time
07:30 - 08:15
Room
Bellevue
Meeting Participant
Extended Abstract (for invited Faculty only) Please select your topic

6.3.1 - The Importance of Cartilage Regeneration: Why, When and How (my Experience With Hyalofast & Nanofx)

Presentation Topic
Please select your topic
Date
13.04.2022
Lecture Time
07:30 - 07:41
Room
Bellevue
Session Type
Industry Satellite Symposium
Extended Abstract (for invited Faculty only) Medication and Cartilage

6.3.2 - OA Pain Management: Investigation Into the Effects on Chondrocytes of Intra - Articular HA, GC and LA

Presentation Topic
Medication and Cartilage
Date
13.04.2022
Lecture Time
07:41 - 07:52
Room
Bellevue
Session Type
Industry Satellite Symposium

Abstract

Introduction

Osteoarthritis (OA) of the knee is a degenerative joint disease characterized by a

low-grade joint infection leading to altered chondrocyte metabolism. In a healthy microenvironment, chondrocytes regulate the composition of the extracellular matrix (ECM) such as collagen II and non-collagen proteins (e.g., aggrecan) via a complex signaling

network of catabolic and anabolic factors. In OA a metabolic shift of the chondrocytes causes a homeostatic imbalance with increased catabolism and apoptosis and reduced anabolism and autophagy leading to disease progression. Intra-articular injections of local anesthetics (LA) are widely used for treating patients suffering from painful OA of the knee. LA are prevalently administered to OA patients for instantaneous pain relief. The problem is that this effect only lasts a couple of days, depending on pharmacokinetics of the respective substance, and only recurrent injections of LA subside persistent pain relief. However, the cytotoxic effects of LA on chondrocytes are well known. Intra-articular injection of LA is contra-productive and intensifies the progression of osteoarthritis. The detrimental impact varies depending on the substance being injected. Some studies have shown that ropivacaine induces less apoptosis of chondrocytes in vitro than other anesthetics like lidocaine or bupivacaine.

Content

LA only treat the symptom, namely pain, and accelerates the degenerative process. In contrast, intra-articular administered glucocorticoids (GC) or hyaluronic acid (HA) target to offset the progression of OA. GC have a potent anti-inflammatory effect which plays a significant role in constraining the progression of OA. However, pro-apoptotic effects of GC on chondrocytes have been reported. This raises the question of whether GC should be administered intra-articular together with local anesthetics because adverse effects on chondrocytes are known for both substances. Interestingly, despite that, their coadministration is frequently performed in clinical practice. HA also has anti-inflammatory effects, albeit to a lesser extent than GC. Advantages of HA include increased cell viability and its role as a viscosupplement for increased lubrication. Furthermore, administered HA induces endogenous HA production. Recently, the co-administration of HA with GC was introduced to combine the beneficial effects of both substances. Primary clinical studies show promising results with decreased pain levels in the co-administration compared to a single injection. Administering different substances offers the potential of achieving synergistic effects and might mitigate detrimental effects of one substance (e.g., cytotoxicity of LA, the apoptotic potential on chondrocytes of GC) by another one (e.g., HA).

The current study aimed to investigate the cytotoxicity of co-administrating local anesthetics (LA) with glucocorticoids (GC) and hyaluronic acid (HA) in vitro. Human articular cartilage

was obtained from five patients undergoing total knee arthroplasty. Chondrocytes were isolated, expanded, and seeded in 24-well plates for experimental testing. LA (lidocaine, bupivacaine, ropivacaine) were administered separately and co-administered with the following substances: GC, HA, and GC/HA. Viability was confirmed by microscopic images, flow cytometry, metabolic activity, and live/dead assay. The addition of HA and GC/HA resulted in enhanced attachment and branched appearance of the chondrocytes compared to LA and LA/GC. Metabolic activity was better in all LA co-administered with HA and GC/HA than with GC and only LA. Flow cytometry revealed the lowest cell viability in lidocaine and the highest cell viability in ropivacaine. This finding was also confirmed by live/dead assay. The study showed that co-administering LA with HA and HA/GC reduces its chondrotoxicity.

Administering GC is desirable due to its potent anti-inflammatory effect, albeit its apoptotic potential is problematic. In the present study, HA supports the effects of GC and reduces the cytotoxic effects of LA. Differences between LA were observed; (i) lidocaine showed high apoptotic rates; (ii) ropivacaine showed the best cell viability. The findings of the present study are of high clinical relevance. Although the chondrotoxic effect of LA and GC is well known, the substances are widely used in a clinical setting. The data of this study suggest that co-administrating HA with LA and GC might mitigate their detrimental effects on chondrocytes while still maintaining the beneficial effects of anti-inflammation.

References

1. Moser LB, Bauer C, Jeyakumar V, Niculescu-Morzsa E-P, Nehrer S. Hyaluronic Acid as a Carrier Supports the Effects of Glucocorticoids and Diminishes the Cytotoxic Effects of Local Anesthetics in Human Articular Chondrocytes In Vitro. Int J Mol Sci. 2021 Oct 25;22(21):11503.

2. Szwedowski D, Szczepanek J, Paczesny Ł, Pękała P, Zabrzyński J, Kruczyński J. Genetics in Cartilage Lesions: Basic Science and Therapy Approaches. International Journal of Molecular Sciences. 2020 Jan;21(15):5430.

3. Sophia Fox AJ, Bedi A, Rodeo SA. The Basic Science of Articular Cartilage. Sports Health. 2009 Nov;1(6):461–8.

4. Zheng L, Zhang Z, Sheng P, Mobasheri A. The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Ageing Res Rev. 2021 Mar;66:101249.

5. Kreuz PC, Steinwachs M, Angele P. Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature. Knee Surg Sports Traumatol Arthrosc. 2018 Mar;26(3):819–30.

6. Breu A, Rosenmeier K, Kujat R, Angele P, Zink W. The cytotoxicity of bupivacaine, ropivacaine, and mepivacaine on human chondrocytes and cartilage. Anesth Analg. 2013 Aug;117(2):514–22.

7. Akmal M, Singh A, Anand A, Kesani A, Aslam N, Goodship A, et al. The effects of hyaluronic acid on articular chondrocytes. J Bone Joint Surg Br. 2005 Aug;87(8):1143–9.

Acknowledgments

The research was supported by unrestricted funding:

Anika Therapeutics Inc., 32 Wiggins Avenue, MA 01730 Bedord, Massachusetts, USA

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Extended Abstract (for invited Faculty only) Joint Specific Cartilage Repair

6.3.3 - Mini-Invasive Knee Joint Replacement: Why Bone Preservation is so Important (Pre-Recorded)

Presentation Topic
Joint Specific Cartilage Repair
Date
13.04.2022
Lecture Time
07:52 - 08:03
Room
Bellevue
Session Type
Industry Satellite Symposium