Synthesis and characterization of injectable, biodegradable, phosphate-containing, chemically cross-linkable, thermoresponsive macromers for bone tissue engineering.
Novel, injectable, biodegradable macromer solutions that form hydrogels when elevated to physiologic temperature via a dual chemical and thermo-gelation were fabricated and characterized. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant phosphate groups was synthesized and subsequently functionalized with chemically cross-linkable methacrylate groups via degradable phosphate ester bonds, yielding a dual-gelling macromer. These dual-gelling macromers were tuned to have transition temperatures between room temperature and physiologic temperature, allowing them to undergo instantaneous thermogelation as well as chemical gelation when elevated to physiologic temperature. Additionally, the chemical cross-linking of the hydrogels was shown to mitigate hydrogel syneresis, which commonly occurs when thermogelling materials are raised above their transition temperature. Finally, degradation of the phosphate ester bonds of the cross-linked hydrogels yielded macromers that were soluble at physiologic temperature. Further characterization of the hydrogels demonstrated minimal cytotoxicity of hydrogel leachables as well as in vitro calcification, making these novel, injectable macromers promising materials for use in bone tissue engineering.
Department of Bioengineering, Rice University 6500 Main Street, Houston, Texas 77030, United States.
Brendan M
BM
Watson
F Kurtis
FK
Kasper
Paul S
PS
Engel
Antonios G
AG
Mikos
D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001842:Bone and Bones / Q000166:cytology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D013696:Temperature; D023822:Tissue Engineering
D000180:Acrylic Resins; D001672:Biocompatible Materials; D020100:Hydrogels; D010710:Phosphates; C052970:poly-N-isopropylacrylamide