title: Controlled in vivo degradation of genipin crosslinked polyethylene glycol hydrogels within osteochondral defects.
abstract: Polyethylene glycol (PEG) hydrogels show promise as scaffolds for growth factor delivery to enhance cartilage repair. However, methods to control growth factor release in vivo are needed. We have recently shown that in vitro polymer degradation and in vitro growth factor release kinetics can be altered using PEG crosslinked with different concentrations of genipin. However, the degradation and behavior of PEG-genipin in vivo within the cartilage repair site are unknown. This study was conducted to test the hypotheses that the degradation of PEG-genipin can be altered in vivo within osteochondral defects by changing the concentration of genipin, and that PEG-genipin is biocompatible within the mammalian diarthrodial environment. PEG-genipin cylindrical polymers crosslinked using 8mM, 17.6 mM, or 35.2 mM of genipin were implanted into osteochondral defects made in the trochlea of 24 male Sprague- Dawley rats (48 knees). Rats were sacrificed at 5 weeks and gross, cross-sectional, and histologic assessments were performed. Altering the genipin concentration changed the in vivo degradation properties of the hydrogel ( p < 0.01). Consistent with in vitro findings, polymer degradation was inversely related to the concentration of genipin. Near-complete degradation was seen at 8 mM, intermediate degradation at 17.6 mM, and minimal degradation at 35.2 mM. The results of this study show the degradation of PEGgenipin can be altered in vivo within osteochondral defects by changing the concentration of genipin and that PEG-genipin is biocompatible within osteochondral defects. This new in vivo data support potential use of PEG-genipin polymer as an innovative delivery system to control in vivo release of growth factors for improving articular cartilage repair.
authors.affiliation: Cartilage Restoration Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Ferretti
authors.forename: Kacey G
authors.initials: KG
authors.lastname: Marra
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Defail
authors.forename: Constance R
authors.initials: CR
authors.lastname: Chu
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002756:Cholagogues and Choleretics / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004343:Drug Implants / Q000737:chemistry / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D057889:Iridoid Glycosides; D039823:Iridoids; D007718:Knee Injuries / Q000473:pathology / Q000628:therapy*; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry; D011714:Pyrans / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001672:Biocompatible Materials; D002756:Cholagogues and Choleretics; D004343:Drug Implants; D057889:Iridoid Glycosides; D039823:Iridoids; D011714:Pyrans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C007834:genipin