title: Hydrogels for osteochondral repair based on photocrosslinkable carbamate dendrimers.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
authors.forename: Lovorka
authors.initials: L
authors.lastname: Degoricija
authors.forename: Prashant N
authors.initials: PN
authors.lastname: Bansal
authors.forename: Serge H M
authors.initials: SH
authors.lastname: Söntjens
authors.forename: Neel S
authors.initials: NS
authors.lastname: Joshi
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Brian
authors.initials: B
authors.lastname: Snyder
authors.forename: Mark W
authors.initials: MW
authors.lastname: Grinstaff
mesh_terms: 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
chemical_list: D002219:Carbamates; D003432:Cross-Linking Reagents; D050091:Dendrimers; D020100:Hydrogels; D046911:Macromolecular Substances; D011092:Polyethylene Glycols
references.citation: Am J Orthop (Belle Mead NJ). 1999 Feb;28(2):88-96
references.pmid: 10067711
references.citation: J Bone Joint Surg Br. 1999 Nov;81(6):1064-8
references.pmid: 10615987
references.citation: Plast Reconstr Surg. 1999 Sep;104(4):1014-22
references.pmid: 10654741
references.citation: Biomaterials. 2000 Mar;21(5):431-40
references.pmid: 10674807
references.citation: Clin Cornerstone. 1999;2(2):26-37
references.pmid: 10689542
references.citation: Phys Med Rehabil Clin N Am. 2000 May;11(2):289-307, vi
references.pmid: 10810762
references.citation: Arthritis Rheum. 2000 Sep;43(9):1916-26
references.pmid: 11014341
references.citation: Annu Rev Biomed Eng. 2000;2:9-29
references.pmid: 11701505
references.citation: Chem Rev. 2001 Dec;101(12):3819-68
references.pmid: 11740922
references.citation: Chem Rev. 1999 Jul 14;99(7):1665-1688
references.pmid: 11849007
references.citation: Chem Rev. 1997 Aug 5;97(5):1681-1712
references.pmid: 11851463
references.citation: J Am Chem Soc. 2002 May 15;124(19):5291-3
references.pmid: 11996569
references.citation: Osteoarthritis Cartilage. 2002 Jun;10(6):432-63
references.pmid: 12056848
references.citation: Biomacromolecules. 2002 Jul-Aug;3(4):710-23
references.pmid: 12099815
references.citation: Biomaterials. 2002 Nov;23(22):4307-14
references.pmid: 12219820
references.citation: Arthritis Rheum. 2002 Sep;46(9):2524-34
references.pmid: 12355501
references.citation: J Biomed Mater Res A. 2003 Jan 1;64(1):70-9
references.pmid: 12483698
references.citation: Chemistry. 2003 Nov 21;9(22):5618-26
references.pmid: 14639645
references.citation: J Am Chem Soc. 2003 Dec 17;125(50):15485-9
references.pmid: 14664594
references.citation: Tissue Eng. 2004 Mar-Apr;10(3-4):515-22
references.pmid: 15165468
references.citation: Arch Ophthalmol. 2004 Jun;122(6):867-70
references.pmid: 15197062
references.citation: J Am Chem Soc. 2004 Oct 13;126(40):12744-5
references.pmid: 15469247
references.citation: J Orthop Res. 2005 Jul;23(4):735-42
references.pmid: 16022984
references.citation: Chem Commun (Camb). 2005 Sep 14;(34):4309-11
references.pmid: 16113731
references.citation: Org Lett. 2005 Oct 27;7(22):4863-6
references.pmid: 16235908
references.citation: Biomacromolecules. 2006 Jan;7(1):310-6
references.pmid: 16398530
references.citation: Bioconjug Chem. 2006 Jul-Aug;17(4):873-6
references.pmid: 16848392
references.citation: Cancer Res. 2006 Dec 15;66(24):11913-21
references.pmid: 17178889
references.citation: Invest Ophthalmol Vis Sci. 2007 May;48(5):2037-42
references.pmid: 17460258
references.citation: Tissue Eng. 2006 Dec;12(12):3285-305
references.pmid: 17518670
references.citation: Biomaterials. 2007 Dec;28(35):5205-14
references.pmid: 17889330
references.citation: Adv Drug Deliv Rev. 2008 Jun 10;60(9):1037-55
references.pmid: 18448187
references.citation: Angew Chem Int Ed Engl. 1999 Apr 1;38(7):884-905
references.pmid: 29711851
references.citation: J Bone Joint Surg Am. 1980 Jan;62(1):79-89
references.pmid: 7351420
references.citation: N Engl J Med. 1994 Oct 6;331(14):889-95
references.pmid: 8078550
references.citation: J Cell Sci. 1994 Jan;107 ( Pt 1):17-27
references.pmid: 8175906
references.citation: Rheum Dis Clin North Am. 1993 Aug;19(3):607-15
references.pmid: 8210577
references.citation: J Biomed Mater Res. 1993 Jan;27(1):11-23
references.pmid: 8380593
references.citation: Plast Reconstr Surg. 1996 Oct;98(5):843-50
references.pmid: 8823024
references.citation: J Biomed Mater Res. 1997 Feb;34(2):211-20
references.pmid: 9029301
references.citation: Arthroscopy. 1997 Feb;13(1):9-17
references.pmid: 9043599
references.citation: Orthopedics. 1998 Jul;21(7):761-7; discussion 767-8
references.pmid: 9672913