Bone is capable of regeneration, and defects often heal spontaneously. However, cartilage, tendon, and ligament injuries usually result in replacement if the site by organized scar tissue, which is inferior to the native tissue. The osteogenic potential of mesenchymal stem cells (MSCs) has already been verified. MSCs hold great potential for the development of new treatment strategies for a host of orthopedic conditions. The multi-lineage potential and plasticity of MSCs allow them to be building blocks for a host of nonhematopoietic tissues, including bone. More recently, several groups have reported on the successful clinical application of tissue engineering strategies in the repair of bony defects in patients secondary to trauma and tumor resection. Advances in fabrication of biodegradable scaffolds that serve as beds for MSC implantation will hopefully lead to better biocompatibility and host tissue integration. Current strategies for bone tissue engineering include the use of osteoconductive matrix devices that promote bony ingrowth, and the delivery of osteoinductive growth factors, including bone morphogenetic protein (BMP) family, BMP-2 and BMP-7, to bony defect sites. Minimal toxicity has been observed in animal models involving genetically-manipulated stem cells transduced with retroviral and adenoviral vectors. Gene therapy using stem cells as delivery vehicles is a powerful weapon that can be used in a plethora of clinical situations that would benefit from the osteoinductive, proliferative, and angiogenic effects of growth factors. With better understanding of the biology of stem cells in the future and with enhancement of technologies that are capable to influence, modify, and culture these cells, a new field of regenerative skeletal medicine may emerge

Gene-activated scaffolds have shown potential in localised gene delivery resulting in bone tissue regeneration. In this study, the ability of two gene delivery vectors, polyethyleneimine (PEI) and nano-hydroxyapatite (nHA), to act as carriers for the delivery of therapeutic genes when combined with our collagen-nHA (coll-nHA) scaffolds to produce gene-activated scaffolds [1, 2], was determined. In addition, coll-nHA-dual gene scaffolds containing both an angiogenic gene and an osteogenic gene were assessed for bone healing in an in vivo Wistar rat calvarial defect model. When cells were applied to the coll-nHA scaffolds under osteogenic conditions in vitro, the dual scaffolds exhibited significantly superior osteogenic potential when analysed using microCT, calcium quantification and histology compared to single-gene scaffolds and gene-free controls. When the dual scaffolds were assessed in vivo, the nHA dual scaffold outperformed all other groups as early as 4 weeks post-implantation as determined using X-ray, microCT, quantification of new bone volume, histology and vessel formation. This research has demonstrated the potential of using novel coll-nHA scaffolds for therapeutic gene therapy while also being capable of simultaneously delivering numerous genes. This study underlines the effect of specifically tailoring gene-activated scaffolds for bone regeneration applications

The key factors in Tissue Engineering are multipotent stem cells, growth factors (necessary to manipulate cell destiny) and scaffolds (3D constructs which support the growing tissue). Mesenchymal stem cells are the most important part of this equation, and it is procurement and manipulation of these that lies at the heart of tissue engineering. Luckily, mensenchymal stem cells can be obtained from many tissues, including synovium, bone marrow and periosteum. The use of bioreactors to optimise culture conditions and improve cell viability provides an opportunity to control stem cell destiny. Various Tissue Engineering strategies exist: manipulating cells in situ with osteogenic growth factors, such as BMP; implanting whole tissue grafts; and the use of Gene therapy. The tissues that concern orthopaedic surgeons are very diverse and no single tissue engineered construct will be able to fulfil all our clinical needs. Tissue engineering of articular cartilage is very difficult technically, but once accomplished will revolutionalise practice. The challenge lies in being able to produce cartilage as similar to native hyaline cartilage as possible. Although promising, ACI, using culture expanded cells, is able at best to produce hyaline-like cartilage but not the real thing. Multipotent mesenchymal stem cells are being used in this field. Even simply injecting these intraarticularly has been shown to retard the progression of OA in animal models. When attempting to regenerate meniscal cartilage, the mechanical properties of the scaffold become crucial, as the biomechanics of the knee are highly hostile. Ligaments and tendons, though the least complex tissues architecturally, have very high tensile properties which will be hard to replicate. The challenging aspects of Orthopaedic Tissue Engineering are manifold, yet the field itself is growing in leaps and bounds. Despite some initial setbacks, the new developments in this discipline are very encouraging