Large, full thickness cartilage defects typically require cell or tissue transplantation to promote regeneration, however current clinical treatments are hampered by a lack of tissue availability and inadequate integration of the transplanted tissue. Tissue engineering offers a solution by creating osteochondral tissues that could be used for transplantation. However, achieving tight integration between engineered bone and cartilage tissues is challenging. The objective of this two-year exploratory project is to address this problem by creating continuous, strong osteochondral interfaces using a modular tissue engineering approach. Discrete microbeads (200-50 in diameter) made from extracellular matrix materials (collagen, chitosan, hydroxyapatite) will be used to encapsulate and control the phenotype of adult human mesenchymal stem cells (hMSC). Osteogenic and chondrogenic populations of microbeads will be created separately and then combined to form cohesive multiphase tissue constructs. Control of the assembly of the component microbeads provides a way to prescribe the organization of the resulting interface. The general hypothesis upon which this project is based is that the architecture of the interface between chondrogenic and osteogenic microbeads can be manipulated to promote integration of these two tissue types, thereby leading to strong and stable osteochondral tissues. This project addresses three specific sub-hypothesis that provide insight into the effects of geometry, scale, and timing of formation of osteochondral interfaces. These hypotheses will be tested through two Specific Aims. In SA1 we will create osteochondral tissues and interfaces by combining chondrogenic and osteogenic microbeads in both layered and continuous architectures. In parallel, SA2 will comprehensively characterize the microbeads and osteochondral constructs at selected time points, with particular emphasis on interfacial organization and strength through biochemical, histological and mechanical assessment. By creating 3D multiphase constructs using the hydrogel microbead approach we expect to achieve enhanced integration of engineered bone and cartilage tissue. The ability to design robust and highly interconnected bone-cartilage constructs could lead to improved treatment of osteochondral defects.

Public Health Relevance

Large cartilage defects do not heal, and current therapeutic options are not adequate for the most challenging cases. A promising approach to this problem is to create engineered tissues that integrate with both bone and cartilage;however it is difficul to obtain a strong connection between these tissues. This project will apply a new approach to this problem;by creating small, modular tissue units that are designed to form both bone and cartilage tissue, and which can be combined into highly integrated multiphase tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR062709-02
Application #
8640078
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2013-05-01
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
$154,583
Indirect Cost
$48,333
Name
University of Michigan Ann Arbor
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Stegemann, J P; Verrier, S; Gebhard, F et al. (2014) Cell therapy for bone repair: narrowing the gap between vision and practice. Eur Cell Mater 27:1-4
Rao, Rameshwar R; Ceccarelli, Jacob; Vigen, Marina L et al. (2014) Effects of hydroxyapatite on endothelial network formation in collagen/fibrin composite hydrogels in vitro and in vivo. Acta Biomater 10:3091-7
Walters, B D; Stegemann, J P (2014) Strategies for directing the structure and function of three-dimensional collagen biomaterials across length scales. Acta Biomater 10:1488-501