Abstract
Articular cartilage (AC) may be affected by many injuries including traumatic lesions that predispose to osteoarthritis. Currently there is no efficient cure for cartilage lesions. In that respect, new strategies for regenerating AC are contemplated with interest. In this context, we aim to develop and characterize an injectable, self-hardening, mechanically reinforced hydrogel (Si-HPCH) composed of silanised hydroxypropymethyl cellulose (Si-HPMC) mixed with silanised chitosan. The in vitro cytocompatibility of Si-HPCH was tested using human adipose stromal cells (hASC). In vivo, we first mixed Si-HPCH with hASC to observe cell viability after implantation in nude mice subcutis. Si-HPCH associated or not with canine ASC (cASC), was then tested for the repair of osteochondral defects in canine femoral condyles. Our data demonstrated that Si-HPCH supports hASC viability in culture. Moreover, Si-HPCH allows the transplantation of hASC in the subcutis of nude mice while maintaining their viability and secretory activity. In the canine osteochondral defect model, while the empty defects were only partially filled with a fibrous tissue, defects filled with Si-HPCH with or without cASC, revealed a significant osteochondral regeneration. To conclude, Si-HPCH is an injectable, self-setting and cytocompatible hydrogel able to support the in vitro and in vivo viability and activity of hASC as well as the regeneration of osteochondral defects in dogs when implanted alone or with ASC.
Highlights
Articular cartilage (AC) is a complex porous permeable extracellular matrix that surrounds specific cell type called chondrocytes
We showed in a dog model of osteochondral defects that it is possible to repair articular cartilage with a hybrid hydrogel made of cellulose- and chitosan-derived polymers
After having shown that associating silanised hydroxypropymethyl cellulose (Si-HPMC) with Si-chitosan led to the formation of a mechanically reinforced hydrogel that can support mesenchymal stromal cells (MSC) viability in vitro and in vivo, we were able to clearly demonstrate the ability of this novel self-setting hydrogel to contribute to the repair of osteochondral defects in a canine model in the absence or presence of MSCs
Summary
Articular cartilage (AC) is a complex porous permeable extracellular matrix that surrounds specific cell type called chondrocytes. AC defects affect approximately two million patients every year in Europe and in the United States (Mumme et al, 2016), and they remain a clinical challenge due to the paucity of routinely translatable therapeutics to treat this condition. Degenerative changes affected the cartilage and the bone surrounding the lesion (Schinhan et al, 2012). Therapeutic options to repair AC defects include microfracture, autologous osteochondral grafting (Brittberg et al, 2016), and autologous chondrocyte implantation. These therapeutic options are, subject to major logistical and clinical issues, such as their short-lived clinical benefits in particular (Vinatier and Guicheux, 2016)
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