Bilayered laponite/alginate-poly(acrylamide) composite hydrogel for osteochondral injuries enhances macrophage polarization: An in vivo study

Addressing osteochondral defects, the objective of current study was to synthesize bilayered hydrogel, where the cartilage layer was formed by alginate (Alg) polyacrylamide (PAAm) with and without the addition of TGF-beta 3 and bone layer by laponite XLS/Alg-PAAm and characterize by in vitro and in vivo experiments. Exceeding the mechanical strength of Alg-PAAm (32.95 +/- 1.23 kPa) and XLS based (317.5 +/- 21.72 kPa) hydrogels, XLS/Alg-PAAm hydrogel (469.7 +/- 6.1 kPa) activated macrophages towards M2 phenotype and stimulated the expression of anti-inflammatory factors. The addition of TGF-beta 3 accelerated transition of macrophage polarization, especially between day 4 and 7. The expression levels of MI-related genes such as CD80, iNOS and TNF-alpha decreased gradually after day 4, reaching lowest values at day 13, whereas the expression levels of M2-related genes, CD206, Argi and SFAT6 significantly increased promoting M2 macrophage polarization, which might be associated with accelerated bone repair. Moreover, bilayer structure exhibited a better cell viability as well as rcpainnent thorough the XIS contents. in vivo histological examinations verified the significant surface regularity and hyaline like tissue formation employment, along with synchronized degradation profile of the hydrogel with tissue healing at the end of 12 weeks. A mechanically durable, biocompatible and immunocompatiblc hydmgcl was formulated to be utilized in bone-cartilage engineering applications.
Scientific and Technological Research Council of Turkey (TUBITAK) [117M843, 219M057]; National Research Foundation of Korea [2017K2A9A1A06037807]; Ministry of Science and ICT [NRF-2018M3A7B4089670]; TUBITAK 2211-A National Graduate Scholarship Program; TUBITAK [2211-A]
This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) under grant number 117M843 and immune response studies under grant 219M057. Y.-W.Kim and J.-Y.Sun were sup-ported under the framework of international cooperation program managed by the National Research Foundation of Korea (2017K2A9A1A06037807, FY2017) . Authors would like to acknowledge Material Technology Develop-ment Program through the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (NRF-2018M3A7B4089670) . E.S and P.S.M gratefully acknowledge the TUBITAK 2211-A National Graduate Scholarship Program.