Multipotent mesenchymal stem cells (MSCs) have been suggested as a suitable cell source for cell-based treatments for diseases such as osteoarthritis due to their ability to differentiate towards chondrogenic and osteogenic lineages. MSCs can be obtained from a variety of tissue sources, are scalable for mass-production and immuno-privileged enabling their use for allogeneic cell therapy. However, recent pre-clinical studies and clinical trials point to the necessity of increasing engraftment and efficacy of MSCs. This review explores how cell surface modification of the cells can improve homing of MSCs and summarises the use of nanoparticles to enable gene delivery by stem cells as well as facilitate in vivo imaging. The use of advanced biomaterials and how they can be applied to reduce the overall dose of MSCs during therapeutic interventions while achieving optimal targeting efficiency of cells to the diseased sites are addressed. Particular attention is paid to methods that improve engraftment of MSCs to cartilage and research describing combinatorial approaches of particle-based cell therapies for improved regeneration of this tissue is reviewed. The use of such approaches will add to the array of potential regenerative therapeutics for treatment of osteoarthritis.