title: Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.
abstract: To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects.
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.|Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, P. R. China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
authors.forename: Zhongning
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Kunal J
authors.initials: KJ
authors.lastname: Rambhia
authors.affiliation: Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, P. R. China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.|Macromolecular Science and Engineering Center, Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D000818:Animals; D002417:Cattle; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007249:Inflammation / Q000188:drug therapy*; D008863:Microspheres; D054118:Nanospheres / Q000008:administration & dosage / Q000737:chemistry*; D009805:Odontogenesis / Q000187:drug effects*; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D012710:Serum Albumin, Bovine; C033616:poly(lactide); D048271:Chitosan
keywords: chitosan; co-delivery; controlled release; microspheres; poly(lactic acid)