Efficacy study of two novel hyaluronic acid-based formulations for viscosupplementation therapy in an early osteoarthrosic rabbit model

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• 作者：Sema Kaderli^a ; ^{sema.kaderli@unige.ch" class="auth_mail" title="E-mail the corresponding author} ; Eric Viguier^b ; ^{eric.viguier@vetagro-sup.fr" class="auth_mail" title="E-mail the corresponding author} ; Dorothé ; e Watrelot-Virieux^b ; ^{dorothee.watrelot@vetagro-sup.fr" class="auth_mail" title="E-mail the corresponding author} ; Thierry Roger^b ; ^{thierry.roger@vetagro-sup.fr" class="auth_mail" title="E-mail the corresponding author} ; Robert Gurny^a ; ^{robert.gurny@unige.ch" class="auth_mail" title="E-mail the corresponding author} ; Leonardo Scapozza^a ; ^{leonardo.scapozza@unige.ch" class="auth_mail" title="E-mail the corresponding author} ; Michael Mö ; ller^a ; ^{michael.moeller@unige.ch" class="auth_mail" title="E-mail the corresponding author} ; Caroline Boulocher^b ; ¹ ; ^{caroline.boulocher@vetagro-sup.fr" class="auth_mail" title="E-mail the corresponding author} ; Olivier Jordan^a ; ¹ ; ^{olivier.jordan@unige.ch" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ACLT ; anterior cruciate ligament transection ; CS ; chitosan ; EPIC-渭CT ; equilibrium partitioning of iodine contrast micro-computed tomography ; FOV ; field of view ; HA ; hyaluronic acid ; HA-4AR ; hyaluronic acid linked to 4-aminoresorcinol ; MMP-3 ; matrix metalloproteinase-3 ; MIP ; maximal intensity projection ; OA ; osteoarthrosis ; PBS ; phosphate buffer saline ; SEM ; scanning electron microscopy ; VS ; viscosupplementation
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：96
• 期：Complete
• 页码：388-395
• 全文大小：1321 K

文摘

Viscosupplementation (VS) is a therapy for osteoarthrosis (OA) consisting of repetitive intra-articular injections of hyaluronic acid (HA). It is known to be clinically effective in relieving pain and increasing joint mobility by restoring joint homeostasis. In this study, the effects of two novel HA-based VS hydrogel formulations were assessed and challenged against a pure HA commercial formulation for the first time and this in a rabbit model of early OA induced by anterior cruciate ligament transection (ACLT). The first formulation tested was a hybrid hydrogel composed of HA and reacetylated chitosan, a biopolymer considered to be chondroprotective, assembled thanks to an ionic shielding. The second formulation consisted of a novel HA polymer grafted with antioxidant molecules (HA-4AR) aiming at decreasing OA oxidative stress and increasing HA retention time in the articulation.

ACLT was performed on rabbits in order to cause structural changes comparable to traumatic osteoarthrosis. The protective effects of the different formulations were observed on the early phase of the pathology in a full randomized and blinded manner. The cartilage, synovial membrane, and subchondral bone were evaluated by complementary investigation techniques such as gross morphological scoring, scanning electron microscopy, histological scoring, and micro-computed tomography were used.

In this study, ACLT was proven to successfully reproduce early OA articular characteristics found in humans. HA and HA-4AR hydrogels were found to be moderately protective for cartilage as highlighted by 渭CT. The HA-4AR was the only formulation able to decrease synovial membrane hypertrophy occurring in OA. Finally, the hybrid HA-reacetylated chitosan hydrogel surprisingly led to increased subchondral bone remodeling and cartilage defect formation. This study shows significant effects of two innovative HA modification strategies in an OA rabbit model, which warrant further studies toward more effective viscosupplementation formulations.