Zhao Yue, Gao Chaohua, Liu Hou, Liu Hangrui, Feng Yubin, Li Zuhao, Liu He, Wang Jincheng, Yang Bai, Lin Quan
State Key Lab of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun130012, China; RC Centre of Excellence for NanoscaleBioPhotonics, Department of Physics and Astronomy, Macquarie University, Sydney, NSW2109, Australia.
Orthopaedic Medical Center, the Second Hospital of Jilin University, Changchun130041, China.
Acta Biomater. 2021 Feb;121:653-664. doi: 10.1016/j.actbio.2020.12.005. Epub 2020 Dec 5.
Rheumatoid arthritis (RA) is a severe inflammatory autoimmune disease, but its treatment has been very difficult. Recently, stem cell-based therapies have opened up possibilities for the treatment of RA. However, the hostile RA pathological conditions impede the survival and differentiation of transplanted cells, and it remains challenging to fabricate a suitable biomaterial for the improvement of stem cells survival, engraftment, and function. Here we construct an optimal scaffold for RA management through the integration of 3D printed porous metal scaffolds (3DPMS) and infliximab-based hydrogels. The presence of rigid 3DPMS is appropriate for repairing large-scale bone defects caused by RA, while the designed infliximab-based hydrogels are introduced because of their self-healable, anti-inflammatory, biocompatible, and biodegradable properties. We demonstrate that the bioengineered composite scaffolds support adipose-derived mesenchymal stem cells (ADSCs) proliferation, differentiation, and extracellular matrix production in vitro. The composite scaffolds, along with ADSCs, are then implanted into the critical-sized bone defect in the RA rabbit model. In vivo results prove that the bioengineered composite scaffolds are able to down-regulate inflammatory cytokines, rebuild damaged cartilage, as well as improve subchondral bone repair. To the best of the authors' knowledge, this is the first time that using the antirheumatic drug to construct hydrogels for stem cell-based therapies, and this inorganic-organic hybrid system has the potential to alter the landscape of RA study.
类风湿性关节炎（RA）是一种严重的炎症性自身免疫疾病，但其治疗一直非常困难。最近，基于干细胞的疗法为RA的治疗开辟了可能性。然而，恶劣的RA病理状况阻碍了移植细胞的存活和分化，并且制造一种合适的生物材料以提高干细胞的存活、植入和功能仍然具有挑战性。在此，我们通过整合3D打印多孔金属支架（3DPMS）和基于英夫利昔单抗的水凝胶构建了一种用于RA治疗的最佳支架。刚性3DPMS的存在适合修复由RA引起的大规模骨缺损，而引入基于英夫利昔单抗设计的水凝胶是因为其具有自愈、抗炎、生物相容和可生物降解的特性。我们证明，这种生物工程复合支架在体外支持脂肪来源的间充质干细胞（ADSC）的增殖、分化和细胞外基质产生。然后将复合支架与ADSC一起植入RA兔模型的临界尺寸骨缺损处。体内结果证明，这种生物工程复合支架能够下调炎性细胞因子，重建受损软骨，并改善软骨下骨修复。据作者所知，这是首次使用抗风湿药物构建用于基于干细胞疗法的水凝胶，并且这种无机-有机杂化系统有可能改变RA研究的局面。
