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A hydrogel reservoir as a self-contained nucleus pulposus cell delivery vehicle for immunoregulation and repair of degenerated intervertebral disc

Yulin Jiang,Juehan Wang,Dan Sun,Zheng Liu,Lin Qi,Meixuan Du,Jing Wang,Yubao Li,Ce Zhu,Yong Huang,Yueming Song,Limin Liu,Ganjun Feng,Li Zhang

The strategies for modulating the local inflammatory microenvironment to inhibit intervertebral disc degeneration (IVDD) have garnered significant interest in recent years. In this study, we developed a "self-contained" injectable hydrogel capable of storing Mg 2+ while carrying nucleus pulposus (NP) cells, with the aim of inhibiting IVDD through immunoregulation . The hydrogel consists of sodium alginate (SA), poly(N-isopropylacrylamide) (PNIPAAm), silicate ceramics (SC), and NP cells. When injected into the NP site, PNIPAAm gelates instantly under body temperature, forming an interpenetrating network (IPN) hydrogel with SA. Ca 2+ released from the SC can crosslink the SA in situ , forming a SA/PNIPAAm hydrogel with an interpenetrating network (IPN) encapsulating the NP cells. Moreover, inside the hydrogel, Mg 2+ released from SC are effectively encapsulated and maintained at a desirable concentration. These Mg 2+ facilitates the local cell matrix synthesis and promotes immunomodulation (upregulating M2 / downregulating M1 macrophage polarization), thus inhibiting the IVDD progression. The proposed hydrogel has biocompatibility and is shown to enhance the expression of collagen II (COL II) and aggrecan . The potential of the injectable hydrogel in IVD repair has also been successfully demonstrated by in vivo studies. Statement of significance • A unique injectable hydrogel consisting of sodium alginate (SA), poly(N-isopropylacrylamide) (PNIPAAm), silicate ceramics (SC) and nucleus pulposus cells, has been created for intervertebral disc repair applications. • This is the first “self-contained” cell delivery system capable of releasing and subsequently storing Mg 2+ in the hydrogel reservoir for localized treatment. • The role of Mg 2+ in regulating the macrophage polarity transformation (from pro-inflammatory M1 to anti-inflammatory M2 phenotype) has been unveiled in the context of intervertebral disc repair.