title: Full-course inhibition of biodegradation-induced inflammation in fibrous scaffold by loading enzyme-sensitive prodrug.
abstract: Biodegradation-induced inflammation in biodegradable scaffold materials is a critical problem to be addressed due to its potential inducement to tissue necrosis, granulomas, or tumor genesis. Here, a facile strategy for on-demand release of anti-inflammatory drugs and full-course inhibition of degradation-induced inflammation was demonstrated by simply loading an esterase-sensitive prodrug into a fibrous scaffold. In this study, drug release from the prodrug-loaded scaffolds showed an enzyme-triggered release process, which led to an initial moderate release of anti-inflammatory drugs and a later-stage degradation-synchronized drug release. This unique release kinetics ingeniously achieved on-demand drug therapy and efficient inhibition of inflammation throughout the biodegradation in vivo. More importantly, the prodrug-loaded scaffolds prepared with different biodegradable polymers (i.e., different biodegradation rates) all showed drug release kinetics that matched to the biodegradation rates and full-course inhibition of inflammation in vivo. Therefore, this method offered a general approach for on-demand release of anti-inflammatory drugs and efficient inhibition of inflammation throughout the biodegradation of different polymeric scaffolds. In addition, the release kinetics in our system showed potentials for "batch release" of multiple drugs in combination therapies as well as provided a feasible hint for the drug therapies of some other symptoms caused by in vivo biodegradation.
authors.affiliation: Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou 215006, PR China; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou 215006, PR China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Pan
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai 200233, PR China.
authors.forename: Shen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou 215006, PR China; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou 215006, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou 215006, PR China; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou 215006, PR China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Rd, Shanghai 200233, PR China.
authors.forename: Cunyi
authors.initials: C
authors.lastname: Fan
authors.affiliation: Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou 215006, PR China; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou 215006, PR China. Electronic address: wgcui80@hotmail.com.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Cui
mesh_terms: D000818:Animals; D004798:Enzymes / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds
chemical_list: D004798:Enzymes; D011355:Prodrugs
keywords: Anti-inflammation; Biodegradation; Drug release; Electrospun fiber; Prodrug