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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 39 - 39
1 Mar 2021
Pavan M Barbera C Galesso D Beninatto R Pluda S
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Osteoarthritis (OA) is a joint degenerative disease leading to chronic pain and disability, thus resulting in a major socioeconomic health burden. OA, which has long been believed to be a cartilage disease, is now considered a whole-joint disorder affecting various anatomical structures, including subchondral bone.

Hyaluronic Acid (HA) is commonly used as intra-articular viscosupplementation therapy for its mechanical features and biological effects. Bisphosphonates (BPs) are antiresorptive agents inhibiting recruitment and maturation of osteoclast precursors and activity of mature osteoclasts in the bone. Pre-clinical evidences in the literature, show that intra-articular BPs could impact on OA progression, slowing down or reversing it. The combination of HA biological and mechanical role and Alendronate (ALD) antiresorptive effect could be an interesting strategy for OA treatment. This study describes the synthesis and characterization of FID-134, a new chemical derivative of HA conjugated with ALD by means of a covalent bond, cleavable in physiological condition.

FID-134 was synthesized starting from 500 kDa HA: chemical structure and functionalization degree with ALD were investigated by NMR and ICP-OES. Kinetics of ALD release from FID-134 was determined in TRIS buffer at 37°C and compared to a simple mixture of HA+ALD. 20mg/mL formulations of FID-134 and HA+ALD were investigated for viscoelastic properties, in absence and presence of Ca2+ ions. The cytotoxicity of FID-134 and free ALD were tested on Saos-2 osteoblasts (ATCC HTB-85) and on primary bovine chondrocytes (PBC) at day 1, 3 and 7. The efficacy of FID-134 was assessed in an inflammatory arthritis in vitro model, where bovine cartilage biopsies were exposed to IL-1β/OSM (10ng/mL) for 3 weeks; at the same time, cartilage explants were treated with FID-134. Collagen release in the surnatants was quantified and compared to controls.

FID-134 structure was confirmed by NMR and the 20% mol/mol functionalization degree was determined by ICP-OES. Only about 50% of total bound ALD was released from FID-134 within 7 days, resulting slower compared to HA+ALD mixture. In presence of Ca2+ ions, viscoelastic properties of FID-134 dramatically improved, while HA+ALD formulation remained unaffected. The cytotoxicity of ALD was evident at 100 μM on Saos-2 and PBC after 3 days, while no cytotoxicity was observed at 7 days with FID-134. In the cartilage explant model, a strong collagen release was detected in inflammatory conditions after 3 weeks; this tendency was reversed, and collagen release halved when FID-134 was added to the biopsies.

The synthesized HA-ALD adduct, FID-134, opens the door for a new approach for OA treatment. The results suggest that FID-134 could be beneficial in cartilage degradation and in restoration of subchondral bone function. Finally, local administration and controlled BP release would likely overcome the drawbacks of ALD oral administration, such as unspecific features and long-term toxic side effects.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_2 | Pages 5 - 5
1 Mar 2021
Zais IE Pavan M Sammali S Chisari E
Full Access

Abstract

Objective

The aim of our systematic review was to report the latest evidence on the effects of CoCr particles on local soft tissue with a focus on its clinical relevance.

Methods

PubMed, Embase, and Cochrane Library databases were screened to perform an extensive review. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical and preclinical results written in English. Relative data were extracted and critically analyzed. PRISMA guidelines were applied, and the risk of bias was assessed, as was the methodological quality of the included studies.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_9 | Pages 32 - 32
1 May 2017
Beninatto R Barbera C Pavan M Galesso D Serena E Elvassore N
Full Access

Background

Hyaluronic acid (HA) hydrogels are becoming an increasingly attractive choice for the creation of new biomaterials useful in wound care, tissue engineering and regenerative medicine, because of their high level of biocompatibility and biodegradability, and for their ability to imitate the environment of the extracellular matrix (ECM). Due to the poor biomechanical properties of native hyaluronan, a variety of chemical modifications have been devised to provide mechanically and chemically stiffer materials.

Methods

In this work, 200 kDa hyaluronic acid was modified with coumarin moieties via a functional linker (FID119) and photo-polymerised into networks through a [2+2] cycloaddition reaction using near-UV light (lmax=365 nm). This method allows to obtain “wall-to-wall” hydrogels starting from moderately viscous solutions. FID119 can therefore be deposited in the cartilage defect as an aqueous solution and can be polymerised in situ after UV irradiation.