Mesenchymal progenitor cells, a multipotent adult stem cell population, have the ability to differentiate into cells of connective tissue lineages, including fat, cartilage, bone and muscle, and therefore generate a great deal of interest for their potential use in regenerative medicine. During development, endochondral bone is formed from a template of cartilage that transforms into bone; however, mature articular cartilage remains in the articulating joints, where its principal role is reducing friction and dispersing mechanical load. Articular cartilage is prone to damage from sports injuries or ageing, which regularly progresses to more serious joint disorders, such as osteoarthritis. Osteoarthritis is a degenerative joint disease characterized by the thinning and eventual wearing of articular cartilage, and affects millions of people worldwide. Due to low chondrocyte motility and proliferative rates, and complicated by the absence of blood vessels, cartilage has a limited ability to self-repair. Current pharmaceutical and surgical interventions fail to generate repair tissue with the mechanical and cellular properties of native host cartilage. The long-term success of cartilage repair will therefore depend on regenerative methodologies resulting in the restoration of articular cartilage that closely duplicates the native tissue. For cell-based therapies, the optimal cell source must be readily accessible with easily isolated, abundant cells capable of collagen type II and sulfated proteoglycan production in appropriate proportions. Although a cell source with these therapeutic properties remains elusive, mesenchymal chondroprogenitors retain their expansion capacity with the promise of reproducing the structural or biomechanical properties of healthy articular cartilage. As current knowledge regarding chondroprogenitors is relatively limited, this review will focus on their origin and therapeutic application.

Heart failure is a significant clinical issue. It is the cause of enormous healthcare costs worldwide and results in significant morbidity and mortality. Cardiac regenerative therapy has progressed considerably from clinical and preclinical studies delivering simple suspensions of cells, macromolecule, and small molecules to more advanced delivery methods utilizing biomaterial scaffolds as depots for localized targeted delivery to the damaged and ischemic myocardium. Here, regenerative strategies for cardiac tissue engineering with a focus on advanced delivery strategies and the use of multimodal therapeutic strategies are reviewed.

With the number of stem cell-based therapies emerging on the increase, the need for novel and 3 efficient delivery technologies to enable therapies to remain in damaged tissue and exert their therapeutic 4 benefit for extended periods, has become a key requirement for their translation. Hydrogels, and in 5 particular, thermoresponsive hydrogels, have the potential to act as such delivery systems. 6Thermoresponsive hydrogels, which are polymer solutions that transform into a gel upon a temperature 7 increase, have a number of applications in the biomedical field due to their tendency to maintain a liquid 8 state at room temperature, thereby enabling minimally invasive administration and a subsequent ability to 9 form a robust gel upon heating to physiological temperature. However, various hurdles must be overcome 10 to increase the clinical translation of hydrogels as a stem cell delivery system, with barriers including their 11 low tensile strength and their inadequate support of cell viability and attachment. In order to address these 12 issues, a methylcellulose based hydrogel was formulated in combination with collagen and beta 13 glycerophosphate, and key development issues such as injectability and sterilisation processes were 14 examined. The polymer solution underwent thermogelation at ~36 o C as determined by rheological analysis, 15 and when gelled, was sufficiently robust to resist significant disintegration in the presence of phosphate 16 buffered saline (PBS) while concomitantly allowing for diffusion of methylene blue dye solution into the 17 gel. We demonstrate that human mesenchymal stem cells (hMSCs) encapsulated within the gel remained 18 viable and showed raised levels of dsDNA at increasing time points, an indication of cell proliferation. 19Mechanical testing showed the "injectability", i.e. force required for delivery of the polymer solution 20 through devices such as a syringe, needle or catheter. Sterilisation of the freeze-dried polymer wafer via 21 gamma irradiation showed no adverse effects on the formed hydrogel characteristics. Taken together, these 22 results indicate the potential of this gel as a clinically translatable delivery system for stem cells and 23 therapeutic molecules in vivo. 24 25

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