Biodegradable and injectable cure-on-demand polyurethane scaffolds for regeneration of articular cartilage.
This paper describes the synthesis and characterization of an injectable methacrylate functionalized urethane-based photopolymerizable prepolymer to form biodegradable hydrogels. The tetramethacrylate prepolymer was based on the reaction between two synthesized compounds, diisocyanato poly(ethylene glycol) and monohydroxy dimethacrylate poly(epsilon-caprolactone) triol. The final prepolymer was hydrated with phosphate-buffered saline (pH 7.4) to yield a biocompatible hydrogel containing up to 86% water. The methacrylate functionalized prepolymer was polymerized using blue light (450 nm) with an initiator, camphorquinone and a photosensitizer, N,N-dimethylaminoethyl methacrylate. The polymer was stable in vitro in culture media over the 28 days tested (1.9% mass loss); in the presence of lipase, around 56% mass loss occurred over the 28 days in vitro. Very little degradation occurred in vivo in rats over the same time period. The polymer was well tolerated with very little capsule formation and a moderate host tissue response. Human chondrocytes, seeded onto Cultispher-S beads, were viable in the tetramethacrylate prepolymer and remained viable during and after polymerization. Chondrocyte-bead-polymer constructs were maintained in static and spinner culture for 8 weeks. During this time, cells remained viable, proliferated and migrated from the beads through the polymer towards the edge of the polymer. New extracellular matrix (ECM) was visualized with Masson's trichrome (collagen) and Alcian blue (glycosaminoglycan) staining. Further, the composition of the ECM was typical for articular cartilage with prominent collagen type II and type VI and moderate keratin sulphate, particularly for tissue constructs cultured under dynamic conditions.
Werkmeister
J A
JA
CSIRO Molecular and Health Technologies, Clayton South, Victoria 3169, Australia. Jerome.werkmeister@csiro.au
Adhikari
R
R
White
J F
JF
Tebb
T A
TA
Le
T P T
TP
Taing
H C
HC
Mayadunne
R
R
Gunatillake
P A
PA
Danon
S J
SJ
Ramshaw
J A M
JA
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002850:Chromatography, Gel; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D007267:Injections; D055595:Mechanical Phenomena / Q000187:drug effects; D008689:Methacrylates / Q000494:pharmacology; D011140:Polyurethanes / Q000494:pharmacology*; D019919:Prosthesis Implantation; D051381:Rats; D012038:Regeneration / Q000187:drug effects*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D001672:Biocompatible Materials; D008689:Methacrylates; D011140:Polyurethanes; D014867:Water; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate