title: In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering.
abstract: In this study, we investigated the mineralization capacity and biocompatibility of injectable, dual-gelling hydrogels in a rat cranial defect as a function of hydrogel hydrophobicity from either the copolymerization of a hydrolyzable lactone ring or the hydrogel polymer content. The hydrogel system comprised a poly(N-isopropylacrylamide)-based thermogelling macromer (TGM) and a polyamidoamine crosslinker. The thermogelling macromer was copolymerized with (TGM/DBA) or without (TGM) a dimethyl-γ-butyrolactone acrylate (DBA)-containing lactone ring that modulated the lower critical solution temperature and thus, the hydrogel hydrophobicity, over time. Three hydrogel groups were examined: (1) 15wt.% TGM, (2) 15wt.% TGM/DBA, and (3) 20wt.% TGM/DBA. The hydrogels were implanted within an 8mm critical size rat cranial defect for 4 and 12weeks. Implants were harvested at each timepoint and analyzed for bone formation, hydrogel mineralization and tissue response using microcomputed tomography (microCT). Histology and fibrous capsule scoring showed a light inflammatory response at 4weeks that was mitigated by 12weeks for all groups. MicroCT scoring and bone volume quantification demonstrated a similar bone formation at 4weeks that was significantly increased for the more hydrophobic hydrogel formulations - 15wt.% TGM and 20wt.% TGM/DBA - from 4weeks to 12weeks. A complementary in vitro acellular mineralization study revealed that the hydrogels exhibited calcium binding properties in the presence of serum-containing media, which was modulated by the hydrogel hydrophobicity. The tailored mineralization capacity of these injectable, dual-gelling hydrogels with hydrolysis-dependent hydrophobicity presents an exciting property for their use in bone tissue engineering applications.
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas, 77251-1892, USA.
authors.forename: Tiffany N
authors.initials: TN
authors.lastname: Vo
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas, 77251-1892, USA.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Ekenseair
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas, 77251-1892, USA.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Spicer
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas, 77251-1892, USA.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Watson
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas, 77251-1892, USA.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Tzouanas
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas, 77251-1892, USA.
authors.forename: Terrence T
authors.initials: TT
authors.lastname: Roh
authors.affiliation: Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas, 77251-1892, USA.|Department of Chemical and Biomolecular Engineering, Rice University, P.O. Box 1892, MS 362, Houston, Texas, 77251-1892, USA.
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry; D000179:Acrylates / Q000737:chemistry; D000180:Acrylic Resins / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D005355:Fibrosis; D020100:Hydrogels; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D007267:Injections; D008422:Materials Testing; D010012:Osteogenesis / Q000187:drug effects*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011916:Rats, Inbred F344; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D013696:Temperature; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography
chemical_list: D000179:Acrylates; D000180:Acrylic Resins; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; C000717609:Tgm2 protein, rat; C546914:dimethyl-gamma-butyrolactone acrylate; C052970:poly-N-isopropylacrylamide; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015107:4-Butyrolactone; D002118:Calcium
keywords: Bone; Poly(N-isopropylacrylamide); Thermogelling; Tissue engineering