Abstract
Viral vector-based therapeutic gene therapy is a potent strategy to enhance the intrinsic reparative abilities of human orthopaedic tissues. However, clinical application of viral gene transfer remains hindered by detrimental responses in the host against such vectors (immunogenic responses, vector dissemination to nontarget locations). Combining viral gene therapy techniques with tissue engineering procedures may offer strong tools to improve the current systems for applications in vivo. The goal of this work is to provide an overview of the most recent systems exploiting biomaterial technologies and therapeutic viral gene transfer in human orthopaedic regenerative medicine. Integration of tissue engineering platforms with viral gene vectors is an active area of research in orthopaedics as a means to overcome the obstacles precluding effective viral gene therapy. In light of promising preclinical data that may rapidly expand in a close future, biomaterial-guided viral gene therapy has a strong potential for translation in the field of human orthopaedic regenerative medicine.
Highlights
Regeneration of injured orthopaedic tissues remains problematic in light of their insufficient or deficient capacity to regenerate at both structural and biomechanical levels.In absence of vascularization, the articular cartilage that allows for load transmission and mobility of the joints has a poor ability for self-repair and lesions resulting fromIn contrast, the hierarchical, vascularized bone with type-I collagen fibers and nanohydroxyapatite matrix for skeletal support and mobility has an intrinsic ability to heal
In light of promising preclinical data that may rapidly expand in a close future, biomaterial-guided viral gene therapy has a strong potential for translation in the field of human orthopaedic regenerative medicine
Gene therapy combined with tissue engineering procedures for the controlled delivery of viral gene vectors is a relatively novel but very promising and achievable field of research for the goal of orthopaedic regenerative medicine
Summary
Regeneration of injured orthopaedic tissues (articular cartilage, bone, meniscus, tendons, ligaments) remains problematic in light of their insufficient or deficient capacity to regenerate at both structural and biomechanical levels. Connective tendons that transmit elastic forces between bone and muscles for locomotion and ligaments between bones for stability, both composed of type-I collagen, may be submitted to injury (tears, ruptures, tendinopathy) that poorly heal, forming a scar tissue of lesser quality or with adhesions [11, 12] and none of the current treatments (suture, grafts, synthetic prostheses) promote a long-term reconstruction of functional tissues In this regard, gene therapy [13] may provide powerful, clinically adapted tools to express therapeutic candidate sequences in orthopaedic lesions in a temporarily and spatially defined manner relative to the direct administration of recombinant agents that generally display very short pharmacological half-lives (minutes to hours) [14,15,16,17,18,19,20]. While nonviral vectors have been long manipulated for human gene therapy [21, 22], viral vectors became the focus of orthopaedic regenerative medicine due to their natural entry pathway in target cells and to their overall higher gene transfer efficiencies [19, 23]
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