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Enhancing joint lubrication, combined with anti\u2010inflammatory therapy, is considered as an effective strategy for osteoarthritis treatment. Herein, based on the ball\u2010bearing\u2010inspired superlubricity and the mussel\u2010inspired adhesion, a superlubricated microsphere, i.e., poly (dopamine methacrylamide\u2010to\u2010sulfobetaine methacrylate)\u2010grafted microfluidic gelatin methacrylate sphere (MGS@DMA\u2010SBMA), is developed by fabricating a monodisperse, size\u2010uniform microsphere using the microfluidic technology, and then a spontaneously modified microsphere with DMA\u2010SBMA copolymer by a one\u2010step biomimetic grafting approach. The microspheres are endowed with enhanced lubrication due to the tenacious hydration layer formed around the charged headgroups (\u2010N<jats:sup>+<\/jats:sup>(CH<jats:sub>3<\/jats:sub>)<jats:sub>2<\/jats:sub>\u2010 and \u2010SO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>) 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 \u03b1 (TNF\u2010\u03b1)\u2010induced chondrocyte degradation in vitro, and further exert a therapeutic effect toward osteoarthritis in vivo.<\/jats:p>","DOI":"10.1002\/smll.202004519","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T07:33:35Z","timestamp":1600328015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Ball\u2010Bearing\u2010Inspired Polyampholyte\u2010Modified Microspheres as Bio\u2010Lubricants Attenuate Osteoarthritis"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9230-7047","authenticated-orcid":false,"given":"Jielai","family":"Yang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 P. 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