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) (CS-g-PLA) copolymers is synthesized with varying lactic acid (LA) and chitosan (CS) weight ratios (LA/CS), self-assembled into nano-scale 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 (BSA) 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.

MGF‐Ct24E‐modified piperazine polymer: A balance of antimicrobial activity and cytotoxicity

“…For example, chitosan oligomers (COS), which were hydrolyzed from chitosan, were characterized and found to be a good antibacterial material . To address limitations for its use as an antibacterial material, chemical modifications were made to COS, such as quaternized chitosan oligomers (QCOS) and so on . A recent study found that QCOS had antimicrobial and antioxidant properties in vitro .…”

Chitosan/nHAC/PLGA microsphere vehicle for sustained release of rhBMP‐2 and its derived synthetic oligopeptide for bone regeneration

“…Allograft could be a better substitute, however, lack of osteogenesis and immunological rejection limited its clinical application. Artificial materials are becoming more attractive and popular in studies for bone graft applications . Various biomimetic tissue engineering approaches in terms of artificial materials have been developed to replace autograft and allograft .…”

“…Artificial materials are becoming more attractive and popular in studies for bone graft applications. 14,15 Various biomimetic tissue engineering approaches in terms of artificial materials have been developed to replace autograft and allograft. 16 The ideal artificial materials in bone tissue engineering need not only biocompatibility, biodegradation and osteoconduction, but also osteoinduction or favorable delivery system for the osteogenic factor.…”

Advanced Scaffolds for Dental Pulp and Periodontal Regeneration

“…A recent study elegantly described a strategy to allow dual drug delivery. 77 A microsphere platform was used to concurrently release fluocinolone acetonide (FA) to suppress inflammation and bone morphogenetic protein 2 (BMP-2) to enhance odontogenic differentiation of DPSCs. A constant linear release of FA, and a rapid BMP-2 release was observed in in vitro systems that reduced inflammation on DPSCs and enhanced differentiation.…”

“…A constant linear release of FA, and a rapid BMP-2 release was observed in in vitro systems that reduced inflammation on DPSCs and enhanced differentiation. 77 …”