This review aims to summarize the recent advances in small molecule compounds and their mechanisms in enhancing chondrocyte proliferation and chondrogenic differentiation of stem cells, which address the problem of acquiring cells for cartilage tissue engineering.

The application of tissue engineering to generate cartilage is limited because of low proliferative ability and unstable phenotype of chondrocytes. The sources of cartilage seed cells are mainly chondrocytes and stem cells. A variety of methods have been used to obtain large numbers of chondrocytes, including increasing chondrocyte proliferation and stem cell chondrogenic differentiation via cytokines, genes, and proteins. Natural or synthetic small molecule compounds can provide a simple and effective method to promote chondrocyte proliferation, maintain a stable chondrocyte phenotype, and promote stem cell chondrogenic differentiation. Therefore, the study of small molecule compounds is of great importance for cartilage tissue engineering. Herein, we review a series of small molecule compounds and their mechanisms that can promote chondrocyte proliferation, maintain chondrocyte phenotype, or induce stem cell chondrogenesis. The studies in this field represent significant contributions to the research in cartilage tissue engineering and regenerative medicine.