Delivery of ۱, ۱۰-Phenanthroline and Cannabidiol Small Molecules Enhances Regeneration of Critical-Sized Radial Bone Defects in Rat

Critical-sized bone defects are a major global health issue inorthopedics and cause mal-unions due to either an inadequatenumber of migrated progenitor cells into the defect site or theirincomplete differentiation into osteogenic precursor cells. Althoughmany attempts have been made to accelerate bone regeneration,an appropriate strategy to regenerate a new bonewith optimum morphology and mechanical performance hasnot yet been introduced. The current study aims to develop anovel construct that contains cannabidiol (CBD) and phenanthroline(Phen)-loaded microsphere to recruit MSCs to the defectsite and induce angiogenesis and regenration of a critical sizeradial defect in a rat model. The scaffolds were fabricated bya freeze-drying technique and characterized in terms of morphology,structure, porosity and degradation rate. The effectsof Phen and CBD delivery on cellular behaviours of viability,attachment, differentiation and angiogenesis were subsequentlyevaluated under in vitro condition. Radiology, histopathologyand histomorphometry analysis of constructs were also performed۴ and ۱۲ weeks post transplantation into the radial defects.Physical characteristics of fabricated scaffolds confirmedthe optimum biocompatibility, biodegradability and suitablemechanical properties of the scaffols. In vitro and in vivo migrationassays displayed a significant MSCs migration in theCBD treated groups. CBD-PLGA-G/nHAp, Phen-PLGA-G/nHAp and Phen-CBD-PLGA-G/nHAp significantly increasedthe osteogenic markers in comparison to the PLGA-G/nHApand negative control groups. Real-time PCR analyses showedthat expression level of angiogenic markers dramatically increasedin scaffolds that contained Phen (P<۰.۰۵). Computedtomography (CT) imaging combined with histomorphometryand IHC analysis showed enhanced bone formation and angiogenesisin all scaffolds compared to PLGA-G/nHAp group.Therefore, spongy scaffold that contained CBD and Phen andhad MSCs recruitment and angiogenesis ability could be utilizedto enhnace bone regeneration of large-sized radial defects.

کلیدواژه ها:

Bone Healing ، Mesenchymal Stem Cell ، Small Molecules ، Scaffold ، Radial Defects