The proposed project aims to develop injectable, in situ hardening cell-polymer constructs for the repair of craniofacial bone defects. In addition to developing biomaterials well suited to this application, the project will also investigate the effect on bone regeneration of a number of critical material and cellular parameters, such that knowledge elucidated from the described studies can be broadly applied to other areas of tissue engineering. The first specific aim of the project is to synthesize and characterize novel injectable hydrogels that undergo physical gelation and chemical crosslinking at body temperature. These hydrogels will also contain calcium-binding domains that are hypothesized to both harden the material after injection and induce osteodifferentiation of encapsulated marrow stromal cells following matrix mineralization. A variety of methods to assess the physicochemical characteristics of the hydrogels will be used, and both in vitro and in vivo testing will be performed to evaluate cytocompatibility, stability, and degradation of the hydrogels. The second specific aim involves investigations of the effect different hydrogel formulations and the resultant physical parameters have on both encapsulated cell viability and bone regeneration within the well-established critical size rat calvarial defect model. Finally, the third specific aim is to investigate the effects that varying cellular parameters such as initial seeding density and the stage of osteodifferentiation of encapsulated marrow stromal cells have on the bone regenerative potential of the hydrogel constructs. In vivo studies are incorporated into each aim of the project such that, in keeping with the long-term goal of developing materials appropriate for clinical applications, efficacy with respect to bone regeneration and construct biocompatibility is assessed at each stage of the study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE017441-03
Application #
7777856
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lumelsky, Nadya L
Project Start
2008-04-10
Project End
2013-02-28
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
3
Fiscal Year
2010
Total Cost
$326,362
Indirect Cost
Name
Rice University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
Vo, Tiffany N; Tatara, Alexander M; Santoro, Marco et al. (2017) Acellular mineral deposition within injectable, dual-gelling hydrogels for bone tissue engineering. J Biomed Mater Res A 105:110-117
Vo, T N; Shah, S R; Lu, S et al. (2016) Injectable dual-gelling cell-laden composite hydrogels for bone tissue engineering. Biomaterials 83:1-11
Vo, Tiffany N; Tabata, Yasuhiko; Mikos, Antonios G (2016) Effects of cellular parameters on the in vitro osteogenic potential of dual-gelling mesenchymal stem cell-laden hydrogels. J Biomater Sci Polym Ed 27:1277-90
Watson, Brendan M; Vo, Tiffany N; Tatara, Alexander M et al. (2015) Biodegradable, phosphate-containing, dual-gelling macromers for cellular delivery in bone tissue engineering. Biomaterials 67:286-96
Henslee, Allan M; Yoon, Diana M; Lu, Benjamin Y et al. (2015) Characterization of an injectable, degradable polymer for mechanical stabilization of mandibular fractures. J Biomed Mater Res B Appl Biomater 103:529-38
Vo, Tiffany N; Ekenseair, Adam K; Spicer, Patrick P et al. (2015) In vitro and in vivo evaluation of self-mineralization and biocompatibility of injectable, dual-gelling hydrogels for bone tissue engineering. J Control Release 205:25-34
Lee, Esther J; Kasper, F Kurtis; Mikos, Antonios G (2014) Biomaterials for tissue engineering. Ann Biomed Eng 42:323-37
Tzouanas, Stephanie N; Ekenseair, Adam K; Kasper, F Kurtis et al. (2014) Mesenchymal stem cell and gelatin microparticle encapsulation in thermally and chemically gelling injectable hydrogels for tissue engineering. J Biomed Mater Res A 102:1222-30
Watson, Brendan M; Kasper, F Kurtis; Mikos, Antonios G (2014) Phosphorous-containing polymers for regenerative medicine. Biomed Mater 9:025014
Vo, Tiffany N; Ekenseair, Adam K; Kasper, F Kurtis et al. (2014) Synthesis, physicochemical characterization, and cytocompatibility of bioresorbable, dual-gelling injectable hydrogels. Biomacromolecules 15:132-42

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