Chiang C.-WChen C.-HManga Y.BHuang S.-CChao K.-MJheng P.-RWong P.-CNyambat BSatapathy M.KChuang E.-Y.KUN-MA0 CHAO2022-04-252022-04-25202111769114https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109183600&doi=10.2147%2fIJN.S274461&partnerID=40&md5=59097215b42f6f7dd3e89b95c500b57ahttps://scholars.lib.ntu.edu.tw/handle/123456789/607551Background and Purpose: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration. Methods: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rhe-ometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompat-ibility and therapeutic efficacy. Results: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups. Conclusion: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications. ? 2021 Chiang et al.Drug formulationGlycol chitosanHyaluronic acidNanoparticlesStrontium ranelatebiomaterialchitosanglycolhyaluronic acidhydrogelisofluranemacrogolmolecular scaffoldnanocarriernanocompositenanoparticlepoly ethylene glycol diacrylatesmall nuclear ribonucleoproteinstrontium ranelateunclassified drugdrug carrierpoly(ethylene glycol)diacrylatethiophene derivativeanesthesiaanimal experimentanimal modelanimal tissueArticlebiocompatibilitybiological activitybone defectbone densitybone regenerationcell interactioncell proliferationcell viabilitycontrolled drug releasecontrolled studycytotoxicitydecorticationdrug delivery systemdrug formulationdrug releaseelectron microscopyencapsulationfluorescence microscopyFourier transform infrared spectroscopyhistologyin vitro studyin vivo studyinflammationinfrared spectroscopylight scatteringmalemicro-computed tomographyMTT assaynonhumanosteoblastosteoporosisratscanning electron microscopyspectroscopyspinal cord regenerationtransmission electron microscopyadministration and dosageanimalcell communicationcell survivalchemistrydelayed release formulationdrug effectLeporidaeparticle sizepharmacologyphysiologyspineultrastructureWistar ratAnimalsBone RegenerationCell CommunicationCell ProliferationCell SurvivalDelayed-Action PreparationsDrug CarriersHyaluronic AcidHydrogelsMaleParticle SizePolyethylene GlycolsRabbitsRats, WistarSpineThiophenes[SDGs]SDG3journal article10.2147/IJN.S274461341884702-s2.0-85109183600