**Abstract**

Hydrogels are splendid biomaterials and play a critical role in multiple applications for disease management via offering a microenvironment for drug metabolism and exerting the bonding effect attribute to the preferable physical and chemical properties. State-of-the-art renewal has indicated the combination of hydrogels with mesenchymal stem/stromal cells (MSCs), which are heterogeneous populations with unique hematopoietic-supporting and immunoregulatory properties. For decades, we and other investigators have demonstrated the promising prospects of MSCs in regenerative medicine, and in particular, for the administration of recurrent and refractory disease. Very recently, we took advantage of the hydrogel/MSC composite for the applications in osteoarthritis, burn wounds, and refractory wounds associated with diabetic foot as well. Strikingly, the composite showed superiority in continuous improvement of the biological functions of the injured areas over hydrogels or MSCs, respectively. Collectively, hydrogel-based biomaterials are of importance for disease treatment and the accompanied regenerative medicine. Therefore, in this chapter, we will summarize the latest updates of hydrogel/MSCs composite in tissue engineering and put forward the direction of hotspot issues in the future including hydrogel/MSC and hydrogel/MSC-exosome in preclinical and clinical studies.

**Keywords:** mesenchymal stem/stromal cells, exosomes, hydrogel scaffolds, tissue engineering, regenerative medicine
