Hydrogels for osteochondral repair based on photocrosslinkable carbamate dendrimers.
First generation, photocrosslinkable dendrimers consisting of natural metabolites (i.e., succinic acid, glycerol, and beta-alanine) and nonimmunogenic poly(ethylene glycol) (PEG) were synthesized divergently in high yields using ester and carbamate forming reactions. Aqueous solutions of these dendrimers were photocrosslinked with an eosin-based photoinitiator to afford hydrogels. The hydrogels displayed a range of mechanical properties based on their structure, generation size, and concentration in solution. All of the hydrogels showed minimal swelling characteristics. The dendrimer solutions were then photocrosslinked in situ in an ex vivo rabbit osteochondral defect (3 mm diameter and 10 mm depth), and the resulting hydrogels were subjected to physiologically relevant dynamic loads. Magnetic resonance imaging (MRI) showed the hydrogels to be fixated in the defect site after the repetitive loading regimen. The ([G1]-PGLBA-MA) 2-PEG hydrogel was chosen for the 6 month pilot in vivo rabbit study because this hydrogel scaffold could be prepared at low polymer weight (10 wt %) and possessed the largest compressive modulus of the 10% formulations, a low swelling ratio, and contained carbamate linkages, which are more hydrolytically stable than the ester linkages. The hydrogel-treated osteochondral defects showed good attachment in the defect site and histological analysis showed the presence of collagen II and glycosaminoglycans (GAGs) in the treated defects. By contrast, the contralateral unfilled defects showed poor healing and negligible GAG or collagen II production. Good mechanical properties, low swelling, good attachment to the defect site, and positive in vivo results illustrate the potential of these dendrimer-based hydrogels as scaffolds for osteochondral defect repair.
Degoricija
Lovorka
L
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Bansal
Prashant N
PN
Söntjens
Serge H M
SH
Joshi
Neel S
NS
Takahashi
Masaya
M
Snyder
Brian
B
Grinstaff
Mark W
MW
D000818:Animals; D002219:Carbamates / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D005269:Femur / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry*; D008027:Light; D046911:Macromolecular Substances; D008297:Male; D008422:Materials Testing; D008968:Molecular Conformation; D010007:Osteochondritis / Q000628:therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D014945:Wound Healing
D002219:Carbamates; D003432:Cross-Linking Reagents; D050091:Dendrimers; D020100:Hydrogels; D046911:Macromolecular Substances; D011092:Polyethylene Glycols
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