Chondrocytes secretome enriched microparticles encapsulated with chondrocyte membrane to facilitate the chondrogenesis of BMSCs and reduce hypertrophy

Co-culture of chondrocytes and mesenchymal stem cells (MSCs) represents an effective way to stimulate the chondrogenesis of MSCs and reduce hypertrophy, but the limited donor site supply and the requirement of two-stage operations are among the major barriers of using autologous chondrocytes in clinical. With recent evidence indicated that the chondrogenic effects of the above co-culture mainly lied on the paracrine secretion, and cell membranes also played crucial roles during the chondrocytes-MSCs interaction, we fabricated a multifunctional design of “artificial chondrocytes” that consists of chondrocytes secretome enriched PLGA microparticles with the encapsulation of chondrocytes’ membrane fragments. The artificial chondrocytes had shown a similar diameter and surface electrical charge of natural chondrocytes, with the preserved key chondrocyte membrane surface proteins and sustainedly released chondrogenic cytokines from chondrocytes secretome to extend their effects in vivo. Consequently, the co-culture studies of artificial chondrocytes and bone marrow MSCs had shown the beneficial effects from both chondrocytes secretome and membrane fragments, which also synergistically facilitated the cell proliferation, chondrogenic genes expression, cartilaginous matrix production, and reduced phenotypic hypertrophy in vitro and in vivo. Together, this study has successfully developed the proof-of-concept design of “artificial chondrocytes”, which could potentially conquer many major barriers of using natural chondrocytes and provided a novel synthetic-cell approach to current therapeutical strategies towards the functional regeneration of articular cartilage.