The Infliximab-Based Self-Healing Hydrogel Composite Scaffold Enhances Stem Cells Survival, Engraftment, and Function in Aiding Rheumatoid Arthritis Management

Abstract

Rheumatoid arthritis (RA) is a severe inflammatory autoimmune disease, but its treatment has been very difficult. Recently, stem cell-based therapies open new options for the treatment of RA. However, the hostile RA pathological conditions impede the survival and differentiation of transplanted cells, and it is still a great challenge to fabricate a new biomaterial for the improvement of stem cells survival, engraftment, and function. Here we construct a new scaffold for RA management through the integration of 3D printing porous metal scaffolds (3DPMS) and infliximab-based hydrogels. The presence of rigid 3DPMS is appropriate for 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 depress 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 for RA study.