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

doi:10.1016/j.actbio.2023.08.023

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

Acta Biomater. 2023 Oct 15:170:303-317. doi: 10.1016/j.actbio.2023.08.023. Epub 2023 Aug 18.

Authors

Yulin Jiang¹, Juehan Wang¹, Dan Sun², Zheng Liu¹, Lin Qi¹, Meixuan Du¹, Jing Wang¹, Yubao Li¹, Ce Zhu¹, Yong Huang¹, Yueming Song¹, Limin Liu¹, Ganjun Feng¹, Li Zhang³

Affiliations

¹ Analytical & Testing Center, Department of Orthopedic Surgery, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610065, China.
² Advanced Composite Research Group (ACRG), School of Mechanical and Aerospace Engineering, Queen's University Belfast, BT9 5AH, UK.
³ Analytical & Testing Center, Department of Orthopedic Surgery, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610065, China. Electronic address: nic1976@scu.edu.cn.

PMID: 37597680
DOI: 10.1016/j.actbio.2023.08.023

Abstract

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 Mg²⁺ 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. Ca²⁺ 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, Mg²⁺ released from SC are effectively encapsulated and maintained at a desirable concentration. These Mg²⁺ 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.

Keywords: Cell delivery; Immunoregulation; Intervertebral disc degeneration; Macrophage polarization; Mg(2+).