Abstract
Osteochondral defects involve both the articular cartilage and the underlying subchondral bone. If left untreated, they may lead to osteoarthritis. Advanced biomaterial-guided delivery of gene vectors has recently emerged as an attractive therapeutic concept for osteochondral repair. The goal of this review is to provide an overview of the variety of biomaterials employed as nonviral or viral gene carriers for osteochondral repair approaches both in vitro and in vivo, including hydrogels, solid scaffolds, and hybrid materials. The data show that a site-specific delivery of therapeutic gene vectors in the context of acellular or cellular strategies allows for a spatial and temporal control of osteochondral neotissue composition in vitro. In vivo, implantation of acellular hydrogels loaded with nonviral or viral vectors has been reported to significantly improve osteochondral repair in translational defect models. These advances support the concept of scaffold-mediated gene delivery for osteochondral repair.
Highlights
Articular cartilage, the gliding tissue covering the ends of all joints, has a reduced ability for repair [1]
Mikos et al showed in a rat osteochondral defect model that implantation of an acellular oligo(poly(ethylene glycol) fumarate) (OPF)-based hydrogel loaded in a spatial fashion with DNAs encoding for runt-related transcription factor 2 (RUNX2) and the sex determining region Y-boxes (SOX) trio complexed with a poly(ethylenimine)-hyaluronic acid (HA) delivery vector significantly improved tissue healing relative to empty hydrogels or either factor alone [136]
Another study examined whether a fibrin PU hybrid scaffold provides a favorable environment for the effective chondrogenic differentiation of human Mesenchymal stromal/stem cells (MSCs) (hMSCs) overexpressing SOX9 via Recombinant Adeno-Associated Viral (rAAV)-mediated gene transfer when cultured in rotating bioreactors in vitro. hMSCs could be modified via rAAV to overexpress SOX9 over an extended period within these scaffolds, leading to an improved cell chondrogenic differentiation in such a hydrodynamic environment relative to control vector treatment [112]
Summary
The gliding tissue covering the ends of all joints, has a reduced ability for repair [1]. Osteochondral defects are areas of joint damage that involve both the articular cartilage and the underlying subchondral bone (Figure 1). Different scaffolds have been used to support the delivery of recombinant genes and gene combinations via gene transfer using both nonviral and viral vectors to target cells relevant of osteochondral tissue engineering and repair in vitro and in vivo. The development of such bioactive osteochondral implants that circumvent the need for ex vivo tissue generation allows for an in situ tissue engineering based on the active transgene product in vivo. The goal of the present article is to provide an overview of the current advances in scaffold-mediated gene delivery for osteochondral repair
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