Mechanical forces are a critical environmental factor in maintaining joint homeostasis, determining cell phenotype, inflammatory responses and a tightly regulated anabolic-catabolic signaling axis essential to cartilage homeostasis. Chondrocytes sense their mechanical environment through numerous direct and indirect mechanisms that regulate cell function in health and degenerative diseases, such as osteoarthritis. Targeted inhibition of mechano-inflammatory signalling pathways or restoration of functional chondroprotective extracellular matrix environments in OA may prevent ECM degradation and promote reparative anabolic processes. Development of self-regulating and mechanically responsive biomaterials and drug delivery systems offer advanced 'on-demand' therapeutic approaches for the treatment of OA.
Recent advances in tissue engineering have made progress toward the development of biomaterials capable of the delivery of growth factors, such as bone morphogenetic proteins, in order to promote enhanced tissue repair. However, controlling the release of these growth factors on demand and within the desired localized area is a significant challenge and the associated high costs and side effects of uncontrolled delivery have proven increasingly problematic in clinical orthopedics. Gene therapy may be a valuable tool to avoid the limitations of local delivery of growth factors. Following a series of setbacks in the 1990s, the field of gene therapy is now seeing improvements in safety and efficacy resulting in substantial clinical progress and a resurgence in confidence. Biomaterial scaffoldmediated gene therapy provides a template for cell infiltration and tissue formation while promoting transfection of cells to engineer therapeutic proteins in a sustained but ultimately transient fashion. Additionally, scaffold-mediated delivery of RNA-based therapeutics can silence specific genes associated with orthopedic pathological states. This review will provide an overview of the current state-of-theart in the field of gene-activated scaffolds and their use within orthopedic tissue engineering applications.
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