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Currently, there is a shortage of effective drug carriers to breach these barriers and achieve efficient tissue and cellular delivery of drugs. In this study, an injectable double positively charged functional hydrogel microsphere with \u201ctargeting cartilage extracellular matrix\u201d, \u201ccartilage penetration\u201d, and \u201ccellular phagocytosis\u201d is designed for matching the structural characteristics of joints, addressing the difficulties of drug delivery in joints. The microspheres could be adsorbed on the negatively charged cartilage surface because of their positively charged poly\u2010lysine surface. Furthermore, the internally loaded positively charged polyamidoamine contained kartogenin, which helped\u00a0further the penetration of\u00a0the cartilage under the guidance of electrical charge. The microspheres could\u00a0release kartogenin for more than 21 days. In\u00a0in vivo experiments, the microspheres effectively improve the efficiency of drug delivery, inhibit the degradation of cartilage matrix and subchondral bone, and delay the development of osteoarthritis. As a double positively charged drug delivery system, the versatile microsphere has great potential for treating osteoarthritis and other diseases.<\/jats:p>","DOI":"10.1002\/smll.202202156","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T13:40:50Z","timestamp":1662212450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Injectable Double Positively Charged Hydrogel Microspheres for Targeting\u2010Penetration\u2010Phagocytosis"],"prefix":"10.1002","volume":"18","author":[{"given":"Jiawei","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Orthopaedics 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. R. 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