Long‐Term Recruitment of Endogenous M2 Macrophages by Platelet Lysate‐Rich Plasma Macroporous Hydrogel Scaffold for Articular Cartilage Defect Repair

After cartilage damage, a large number of monocytes/macrophages infiltrate into adjacent synovium and the resident macrophages in synovial tissue transform to activated macrophages (M1), which secrete pro-inflammatory cytokines to induce sustained inflammation and chondrocyte apoptotic. However, current clinical therapies for cartilage repair can rarely achieve long-term anti-inflammatory regulation and satisfactory outcomes. Herein, a platelet lysate-rich plasma macroporous hydrogel (PLPMH) scaffold with around 100 µm pore size and 1.25 MPa Young's modulus is developed to sustainedly recruit and polarize endogenous anti-inflammatory macrophages (M2) for improving cartilage defect repair. PLPMH scaffold can steadily release sphingosine1-phosphate and proteins via gradual degradation, thus inducing M2 macrophages migration or resting (M0) macrophages migration and then polarization to M2 phenotype, and improving the secretion of anti-inflammatory cytokines. Furthermore, PLPMH scaffold exhibits negligible inflammatory responses in vivo and promotes endogenous M2 macrophage infiltration in large numbers and long-time duration to provide a local anti-inflammatory microenvironment, which even lasts for 42 d. In a rabbit model of cartilage defect, PLPMH scaffold increases the ratio of M2 macrophages and improves cartilage tissue regeneration. These studies support that PLPMH scaffold may have a great potential in articular cartilage tissue engineering by providing an anti-inflammatory and pro-regenerative microenvironment.