title: Biodegradable, phosphate-containing, dual-gelling macromers for cellular delivery in bone tissue engineering.
abstract: Injectable, biodegradable, dual-gelling macromer solutions were used to encapsulate mesenchymal stem cells (MSCs) within stable hydrogels when elevated to physiologic temperature. Pendant phosphate groups were incorporated in the N-isopropyl acrylamide-based macromers to improve biointegration and facilitate hydrogel degradation. The MSCs were shown to survive the encapsulation process, and live cells were detected within the hydrogels for up to 28 days in vitro. Cell-laden hydrogels were shown to undergo significant mineralization in osteogenic medium. Cell-laden and acellular hydrogels were implanted into a critical-size rat cranial defect for 4 and 12 weeks. Both cell-laden and acellular hydrogels were shown to degrade in vivo and help to facilitate bone growth into the defect. Improved bone bridging of the defect was seen with the incorporation of cells, as well as with higher phosphate content of the macromer. Furthermore, direct bone-to-hydrogel contact was observed in the majority of implants, which is not commonly seen in this model. The ability of these macromers to deliver stem cells while forming in situ and subsequently degrade while facilitating bone ingrowth into the defect makes this class of macromers a promising material for craniofacial bone tissue engineering.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Watson
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Tiffany N
authors.initials: TN
authors.lastname: Vo
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Tatara
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77030, USA.
authors.forename: Sarita R
authors.initials: SR
authors.lastname: Shah
authors.affiliation: Department of Statistics, Rice University, Houston, TX 77251, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
authors.affiliation: Department of Chemistry, Rice University, Houston, TX 77251, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Engel
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77030, USA. Electronic address: mikos@rice.edu.
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D020100:Hydrogels / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D018613:Microscopy, Confocal; D010710:Phosphates / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D055114:X-Ray Microtomography
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D010710:Phosphates; D011108:Polymers; D004247:DNA; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: Hydrogel; Mesenchymal stem cell encapsulation; Monoacryloxyethyl phosphate; Poly(N-isopropyl acrylamide); Rat cranial defect