Ball-Bearing-Inspired Polyampholyte-Modified Microspheres as Bio-Lubricants Attenuate Osteoarthritis

Abstract

Osteoarthritis, a lubrication dysfunction related disorder in joint, is characterized by articular cartilage degradation and joint capsule inflammation. Enhancing joint lubrication, combined with anti-inflammatory therapy, is considered as an effective strategy for osteoarthritis treatment. Herein, based on the ball-bearing-inspired superlubricity and the mussel-inspired adhesion, a superlubricated microsphere, i.e., poly (dopamine methacrylamide-to-sulfobetaine methacrylate)-grafted microfluidic gelatin methacrylate sphere (MGS@DMA-SBMA), is developed by fabricating a monodisperse, size-uniform microsphere using the microfluidic technology, and then a spontaneously modified microsphere with DMA-SBMA copolymer by a one-step biomimetic grafting approach. The microspheres are endowed with enhanced lubrication due to the tenacious hydration layer formed around the charged headgroups (-N⁺ (CH₃ )₂ - and -SO₃^- ) of the grafted poly sulfobetaine methacrylate (pSBMA), and simultaneously are capable of efficient drug loading and release capability due to their porous structure. Importantly, the grafting of pSBMA enables the microspheres with preferable properties (i.e., enhanced lubrication, reduced degradation, and sustained drug release) that are highly desirable for intraarticular treatment of osteoarthritis. In addition, when loaded with diclofenac sodium, the superlubricated microspheres with excellent biocompatibility can inhibit the tumor necrosis factor α (TNF-α)-induced chondrocyte degradation in vitro, and further exert a therapeutic effect toward osteoarthritis in vivo.

Keywords: drug release; hydrogels; microfluidic technology; osteoarthritis; superlubricated microspheres.