Abstract
Oral tissue regeneration has received growing attention for improving the quality of life of patients. Regeneration of oral tissues such as alveolar bone and widely defected bone has been extensively investigated, including regenerative treatment of oral tissues using therapeutic cells and growth factors. Additionally, small-molecule drugs that promote bone formation have been identified and tested as new regenerative treatment. However, treatments need to progress to realize successful regeneration of oral functions. In this review, we describe recent progress in development of regenerative treatment of oral tissues. In particular, we focus on cyclodextrin (CD)-based pharmaceutics and polyelectrolyte complexation of growth factors to enhance their solubility, stability, and bioactivity. CDs can encapsulate hydrophobic small-molecule drugs into their cavities, resulting in inclusion complexes. The inclusion complexation of osteoinductive small-molecule drugs improves solubility of the drugs in aqueous solutions and increases in vitro osteogenic differentiation efficiency. Additionally, various anionic polymers such as heparin and its mimetic polymers have been developed to improve stability and bioactivity of growth factors. These polymers protect growth factors from deactivation and degradation by complex formation through electrostatic interaction, leading to potentiation of bone formation ability. These approaches using an inclusion complex and polyelectrolyte complexes have great potential in the regeneration of oral tissues.
Highlights
The oral cavity plays a pivotal role in the maintenance of life through ingestion, chewing, and swallowing of food, as well as speech and articulation
The osteogenic differentiation ability of sulfonated PRX (S-PRX)/Bone morphogenetic protein (BMP)-2 complexes (BMP-2: 100 ng/mL) in MC3T3-E1 cells was evaluated by measuring the secretion of alkaline phosphatase phosphatase (ALP) and comparing this with heparin/BMP-2 complex
The amount of ALP produced by treatment with S-PRX/BMP-2 complex was significantly higher than that of the treatment with heparin/BMP-2 complex. These results indicated that S-PRX has a superior ability to enhance BMP-2-induced osteogenic differentiation compared with heparin
Summary
The oral cavity plays a pivotal role in the maintenance of life through ingestion, chewing, and swallowing of food, as well as speech and articulation. Drugs that stimulate tissue regeneration have been considered as potential candidates for dental tissue regeneration These therapeutic cells and molecules sometimes show insufficient regenerative effects owing to insufficient engraftment, deactivation, degradation, rapid elimination from the site of injection, and excretion from the body. Some clinically approved therapeutic proteins are encapsulated in the biodegradable polymer matrix These scaffolds and drug carriers can encapsulate therapeutic molecules to maintain their biological activities, while releasing encapsulated payloads through diffusion, matrix degradation, and other mechanisms [11,12]. These biomaterial-based approaches are crucial for successful treatment. We describe recent approach for enhancing the bioactivity of therapeutic molecules through the formation of an inclusion complex with cyclodextrins (CDs) and complexation with CD-based supramolecular polymers
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