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Multifunctional hydrogel modulates the immune microenvironment to improve allogeneic spinal cord tissue survival for complete spinal cord injury repair

免疫系统 透明质酸 脊髓损伤 移植 脊髓 明胶 医学 软骨 炎症 药理学 免疫学 癌症研究 化学 外科 解剖 生物化学 精神科
作者
Xu Gao,Zhifeng You,Yue Li,Xinyi Kang,Wen Yang,Huiru Wang,Ting Zhang,Xinhao Zhao,Yifu Sun,He Shen,Jianwu Dai
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:155: 235-246 被引量:15
标识
DOI:10.1016/j.actbio.2022.11.015
摘要

Transplantation of allogeneic adult spinal cord tissues (aSCTs) to replace the injured spinal cord, serves as a promising strategy in complete spinal cord injury (SCI) repair. However, in addition to allograft immune rejection, damage-associated molecular pattern (DAMP)-mediated inflammatory microenvironments greatly impair the survival and function of transplants. In this study, we aimed to regulate the immune microenvironment after aSCT implantation by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. The F-G/H hydrogel exhibited the capacities of DAMP scavenging, sustainably released anti-inflammatory cytokines, and reduced lymphocyte accumulation, thereby modulating the immune response and enhancing the survival and function of aSCTs. When the hydrogel was used in combination with a systemic immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. This biomaterial-based immunomodulatory strategy may provide the potential for spinal cord graft replacement for treating SCI. In this study, we aimed to regulate the immune microenvironment by developing a functional hybrid gelatin and hyaluronic acid hydrogel (F-G/H) modified with cationic polymers and anti-inflammatory cytokines that can gelatinize at both ends of the aSCT to glue the grafts for perfect matching at defects. We found that with the treatment of F-G/H hydrogel, the aSCT survival and function was significantly improved, as a result of reducing recruitment and activation of immune cells through TLR- and ST-2- related signaling. With the combination of immunosuppressive drug treatment, the locomotor functions of SCI rats were significantly improved after aSCTs and F-G/H transplantation. Findings from this work suggest the potential application of the F-G/H as a biomaterial-based immunoregulatory strategy for improving the therapeutic efficiency of the transplanted spinal cord graft for spinal cord injury repair.
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