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However, the short half\u2010life of antagonist bioactivity creates challenges for their clinical application. Herein, bovine serum albumin nanoparticles (BNP) encapsulating recombinant human soluble tumor necrosis factor (TNF) receptor type II (rhsTNFRII) are grafted onto microfluidic poly(<jats:sc>l<\/jats:sc>\u2010lactic acid) (PLLA) porous microspheres through chemical bonds, constructing antagonist\u2010functionalized injectable porous microspheres (MS\u2010BNP) for in situ injection into the nucleus pulposus (NP), aimed at regulating the metabolic balance of ECM, thus inhibiting intervertebral disc degeneration. Several binding sites within the BNPs improve encapsulation efficiency, promote the sustained release of rhsTNFRII, and regulate ECM metabolism in the NP. Moreover, PLLA porous microspheres display excellent injectability and porosity and demonstrate efficient and uniform loading of nanoparticles through chemical grafting. By delivering MS\u2010BNP into the NP, a suitable environment is created in situ. Immunohistochemical analysis at 4 and 8 weeks shows that compared with other experimental groups, the expression of TNF\u2010\u03b1 is significantly inhibited for 6.11\u201315.65 folds and 4.59\u201322.14 folds, respectively, and a significant regeneration in NP occurred. This work proposes a novel porous microsphere therapy functionalized by antagonist molecules for the treatment of ECM metabolic disorders, caused by chronic inflammatory responses.<\/jats:p>","DOI":"10.1002\/adfm.202006333","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T03:29:02Z","timestamp":1601263742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Metabolism Balance Regulation via Antagonist\u2010Functionalized Injectable Microsphere for Nucleus Pulposus Regeneration"],"prefix":"10.1002","volume":"30","author":[{"given":"Yichang","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Orthopedic Institute The First Affiliated Hospital of Soochow University  708 Renmin Rd Suzhou Jiangsu 215006 P.R. 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China"}]},{"given":"Jincheng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Orthopedic Institute The First Affiliated Hospital of Soochow University  708 Renmin Rd Suzhou Jiangsu 215006 P.R. China"}]},{"given":"Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Orthopedic Institute The First Affiliated Hospital of Soochow University  708 Renmin Rd Suzhou Jiangsu 215006 P.R. China"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine  197 Ruijin 2nd Road Shanghai 200025 P. R. 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