From:  Advances in bone tissue engineering using biomaterial based scaffolds, purine crosslinking and Wnt signaling
 

Summary of bone related effects of GSK3 inhibitors, AZD2858, BIO, and LiCl in pre-clinical fracture and defect models. Reproduced from Ref. [234] with permission from Elsevier

SpeciesModelsTreatmentDoseHealing and StrengthMajor FindingsRefs
MiceFemur FractureAZD2858 controlled release
AZD2858 injection		0.168 mg↑ BV/TV, strength
↔ BV/TV		Nanoparticles from controlled release over 9 days showed greater accumulation in fracture bone and accelerated fracture healing (4 weeks)
At same dose, free AZD failed to accelerate bone healing		[241]
Femur Fracture6BIO controlled release
6BIO injection		6.9 nmol/kg↑ BV/TV
↔ BV/TV		Micellar delivery of 6BIO controlled release over 7 days showed accelerated fracture healing compared with free 6BIO and control (3wks)
At same dose, free 6BIO failed to accelerate bone healing		[242]
Femur Gap Defect6BIO controlled release
6BIO injection		198 μm↔ BV/TV
↔ BV/TV		Polymeric nanoparticles showed greater accumulation in fractured bone but failed to improve bone healing (3 wks)
At same dose, free 6BIO failed to accelerate bone healing		[243]
Tibia Fracture6BIO injection0.75 mg/kg↔ callus volumeFree 6BIO failed to accelerate bone healing (3 wks)[244]
Tibial FractureLiCl PO200 mg/kg↑ BV/TVLithium impaired bone healing when started before fracture and enhanced repair when started 4 days after the injury[245]
Tibial FractureLiCl injections100 mg/kg↔ strengthNo effect on bone strength (2 wks)[79]
Femur FractureLiCl PO200 mg/kg↑ BV/TV, strengthAccelerated bone healing and bone strength (3 wks)[246]
Femur FractureLiCl20 mg/kg↑ BMD, strengthMaximal healing and strength occurred with a low dose (20 mg/kg) dose given for a longer time (2 wks) with a 7d of onset (4 wks)[247]
RatsFemur FractureLiCl20 mg/kg↑ strengthBest regimen corresponds to a low dose of 20 mg/kg given at 7d of onset for 2 wks duration (4 wks)[80]
Tibial Gap DefectLi2CO3 (localized)10 mM↑ strengthAccelerated bone healing (2 wks)[81]
Femur FractureAZD2858 PO daily30 μmol/kg↑ BMD, strengthAccelerated healing through intramembranous repair without the formation of cartilage (3 wks)[82]
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