STS delivery PCL-MECM based hydrogel hybrid scaffold promote meniscal regeneration through controlling the phenotype of macrophages

Background: Meniscus injury has a limited ability to heal itself and often results in the progression to osteoarthritis. Tissue engineering offers the possibility of regeneration of severely damaged meniscus. Immunomodulatory strategies based on biomaterials have a wide range of regenerative potential. Macrophages have a high degree of plasticity and will change in morphology and function under the influence of different tissues. M1 macrophages have pro-inflammatory properties, while M2 macrophages have tissue repair and remodeling functions. It has been reported many times that biological scaffolds induce M2 polarization, resulting in the increase of the M2: M1 macrophage phenotypic ratio, thereby promoting tissue repair. However, there is no report on meniscus repair and regenerative. Results: In this study, sodium tanshinone IIA sulfonate (STS) delivery Polycaprolactone (PCL)-meniscus extracellular matrix (MECM) based hydrogel hybrid scaffold was fabricated. PCL provides mechanical support, MECM based hydrogel provides a microenvironment conducive to cell proliferation and differentiation, and STS is used to control the phenotype of macrophages. In vitro experiments, we confirmed that STS could not only transform macrophages from M1 to M2 polarization but also prevent meniscal fibrochondrocytes (MFCs) from oxidative stress, apoptosis, and extracellular matrix degradation induced by inflammatory stimulation, thus having stronger proliferation activity. Results of subcutaneous implantation in vivo showed that hybrid scaffold could induce M2 polarization in the early stage. In addition, a hybrid scaffold seeded with MFCs could achieve good meniscus regeneration and chondroprotective effects in the rabbit. Conclusion: STS delivery PCL-MECM based hydrogel hybrid scaffold promotes meniscal regeneration through controlling the phenotype of macrophage, which provides a new direction for tissue engineering meniscus regeneration.