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Precisely Localized Bone Regeneration Mediated by Marine-Derived Microdroplets with Superior BMP-2 Binding Affinity

Authors
Jeon, Eun YoungUm, Seung-HoonPark, JaehoJung, YoungmeeCheon, Cheol-HongJeon, HojeongChung, Justin J.
Issue Date
6월-2022
Publisher
WILEY-V C H VERLAG GMBH
Keywords
bone morphogenetic protein-2; complex coacervates; fucoidan; localized bone regeneration; therapeutic protein delivery
Citation
SMALL, v.18, no.24
Indexed
SCIE
SCOPUS
Journal Title
SMALL
Volume
18
Number
24
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/142997
DOI
10.1002/smll.202200416
ISSN
1613-6810
Abstract
Prompt and robust bone regeneration has been clinically achieved using supraphysiological doses of bone morphogenetic protein-2 (BMP-2) to overcome the short half-life and rapid clearance. However, uncontrolled burst release of exogenous BMP-2 causes severe complications such as heterotopic ossification and soft tissue inflammation. Therefore, numerous researches have focused on developing a new BMP-2 delivery system for a sustained release profile by immobilizing BMP-2 in various polymeric vehicles. Herein, to avoid denaturation of BMP-2 and enhance therapeutic action via localized delivery, a complex coacervate consisting of fucoidan, a marine-derived glycosaminoglycan, and poly-l-lysine (PLL) is fabricated. Superior BMP-2 binding ability and electrostatic interaction-driven engulfment enable facile and highly efficient microencapsulation of BMP-2. The microencapsulation ability of the coacervate significantly improves BMP-2 bioactivity and provides protection against antagonist and proteolysis, while allowing prolonged release. Moreover, BMP-2 containing coacervate is coated on conventional collagen sponges. The bioactivity and localized bone regenerating ability are confirmed through in vitro (human-derived stem cells), and in vivo (calvarial bone defect model) evaluations.
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