There are a limited number of options for clinical surgeons who are faced with reconstructing bone defects that result from congenital anomalies, trauma, infection, and oncologic resection. Current grafting techniques and materials each have their own limitations and drawbacks. For this reason, we aim to create improved bone grafting materials that will act as scaffolds to recruit cells from surrounding tissues and promote natural bone regeneration processes. Using a versatile and robust thiol-ene polymerization scheme developed in the Anseth and Bowman laboratories, we are able to create 3-dimensional matrices containing simple cell adhesion mimics and enzymatically-degradable linkages. As a result, these materials support cellular infiltration and are replaced as new tissue is formed by the body. The research proposed herein will aim to engineer these grafting materials for bone regeneration purposes, first by increasing the ability of cells from the body to migrate into these materials, and then by incorporating signals that tell the invading cells to become bone.
Three specific aims are outlined:
Aim I : Identify biological epitopes and functionalities that influence the rate of migration of cells into and through thiol-ene polymer scaffolds.
Aim II : Develop thiol-ene polymer scaffolds that promote osteogenic differentiation and deposition of a mineralized matrix.
Aim III : Demonstrate the ability of injectable polymer scaffolds developed in Aims I &II to promote bone regeneration in vivo. Successful completion of these Aims should significantly advance our understanding of how to design synthetic polymer scaffolds to enhance natural bone regeneration processes, and this material platform should be readily tailored for applications towards regenerating tissues beyond bone, as well as providing specific advantages for future directions in the design of cell delivery vehicles.

Public Health Relevance

The Anseth Group aims to develop synthetic materials for repairing bone defects resulting from congenital anomalies, trauma, infection, and cancer. Our approach is to create 3-dimensional matrices that will act as scaffolds to recruit cells from surrounding tissues and promote natural bone regeneration processes, creating an improved and bioactive bone graft material.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE016523-09
Application #
8584990
Study Section
Special Emphasis Panel (ZRG1-MOSS-C (03))
Program Officer
Lumelsky, Nadya L
Project Start
2005-05-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
9
Fiscal Year
2014
Total Cost
$347,310
Indirect Cost
$109,810
Name
University of Colorado at Boulder
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Rosales, Adrianne M; Vega, Sebastián L; DelRio, Frank W et al. (2017) Hydrogels with Reversible Mechanics to Probe Dynamic Cell Microenvironments. Angew Chem Int Ed Engl 56:12132-12136
Brown, Tobin E; Anseth, Kristi S (2017) Spatiotemporal hydrogel biomaterials for regenerative medicine. Chem Soc Rev 46:6532-6552
Ma, Hao; Killaars, Anouk R; DelRio, Frank W et al. (2017) Myofibroblastic activation of valvular interstitial cells is modulated by spatial variations in matrix elasticity and its organization. Biomaterials 131:131-144
Caldwell, Alexander S; Campbell, Gavin T; Shekiro, Kelly M T et al. (2017) Clickable Microgel Scaffolds as Platforms for 3D Cell Encapsulation. Adv Healthc Mater 6:
Yang, Chun; DelRio, Frank W; Ma, Hao et al. (2016) Spatially patterned matrix elasticity directs stem cell fate. Proc Natl Acad Sci U S A 113:E4439-45
Magin, Chelsea M; Alge, Daniel L; Anseth, Kristi S (2016) Bio-inspired 3D microenvironments: a new dimension in tissue engineering. Biomed Mater 11:022001
Rosales, Adrianne M; Anseth, Kristi S (2016) The design of reversible hydrogels to capture extracellular matrix dynamics. Nat Rev Mater 1:
Kyburz, Kyle A; Anseth, Kristi S (2015) Synthetic mimics of the extracellular matrix: how simple is complex enough? Ann Biomed Eng 43:489-500
Sridhar, Balaji V; Dailing, Eric A; Brock, J Logan et al. (2015) A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition. Regen Eng Transl Med 1:11-21
Grim, Joseph C; Marozas, Ian A; Anseth, Kristi S (2015) Thiol-ene and photo-cleavage chemistry for controlled presentation of biomolecules in hydrogels. J Control Release 219:95-106

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