Bone scaffolds should provide adequate load bearing and enhance tissue regeneration. However, at present, there is little rigorous comparative information that will tell one that a given material with a given architecture design will provide adequate load bearing and give the best bone regeneration. As a starting point, we associate load bearing with effective elasticity and strength, and enhanced tissue regeneration with permeability material as design variables. Then the fundamental question becomes """"""""can scaffolds be designed to maintain minimum loading bearing characteristics while maximizing permeability and how important is permeability for bone regeneration relative to material osteoconductivity?"""""""" We hypothesize that Bone tissue engineering scaffolds should be fabricated from the most osteoconductive material with maximal permeability to enhance bone regeneration. Furthermore, the scaffold design should be such that the mechanical properties at time 0 can achieve a modulus of 50 MPa and compressive strength of 2 MPa, within the range of human trabecular bone. Related to this hypothesis, we seek to answer the questions: 1) can scaffolds be designed to meet the minimum 50/2 MPa stiffness/strength criteria and how does degradation of these mechanical properties depend on permeability and material?, and 2) does permeability play a significant role in bone regeneration or is material an overwhelming factor? We will answer these fundamental scaffold design questions through three specific aims:
Specific Aim 1 : Computationally design and fabricate scaffolds architectures from HA/TCP, PLLA, and PCL at a single porosity of 60% with maximal and sub-maximal permeability Specific Aim 2: Determine elastic modulus and ultimate strength of designed scaffolds at 0 meet minimum human trabecular bone values. Determine how design/material influence degradation of mechanical properties.
Specific Aim 3 : Determine the influence of designed permeability and material on bone regeneration in a mouse model at 8, and 16 weeks by delivering BMP-7 transduced human fibroblasts. This study will give bone tissue engineers critical information as to as to the relative importance of scaffold permeability and material bone tissue scaffold design, which will be crucial for clinical bone tissue engineering applications. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR053379-02
Application #
7477348
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2007-08-01
Project End
2012-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2008
Total Cost
$357,147
Indirect Cost
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
Saito, Eiji; Suarez-Gonzalez, Darilis; Murphy, William L et al. (2015) Biomineral coating increases bone formation by ex vivo BMP-7 gene therapy in rapid prototyped poly(L-lactic acid) (PLLA) and poly(?-caprolactone) (PCL) porous scaffolds. Adv Healthc Mater 4:621-32
Saito, Eiji; Liao, Elly E; Hu, Wei-Wen et al. (2013) Effects of designed PLLA and 50:50 PLGA scaffold architectures on bone formation in vivo. J Tissue Eng Regen Med 7:99-111
Saito, Eiji; Suarez-Gonzalez, Darilis; Rao, Rameshwar R et al. (2013) Use of micro-computed tomography to nondestructively characterize biomineral coatings on solid freeform fabricated poly (L-lactic acid) and poly ((?-caprolactone) scaffolds in vitro and in vivo. Tissue Eng Part C Methods 19:507-17
Jeong, Claire G; Zhang, Huina; Hollister, Scott J (2012) Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein-2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo without accelerated endochondral ossification. J Biomed Mater Res A 100:2088-96
Kang, Heesuk; Long, Jason P; Urbiel Goldner, Gary D et al. (2012) A paradigm for the development and evaluation of novel implant topologies for bone fixation: implant design and fabrication. J Biomech 45:2241-7
Saito, Eiji; Liu, Yifei; Migneco, Francesco et al. (2012) Strut size and surface area effects on long-term in vivo degradation in computer designed poly(L-lactic acid) three-dimensional porous scaffolds. Acta Biomater 8:2568-77
Hollister, Scott J; Murphy, William L (2011) Scaffold translation: barriers between concept and clinic. Tissue Eng Part B Rev 17:459-74
Jeong, Claire G; Zhang, Huina; Hollister, Scott J (2011) Three-dimensional poly(1,8-octanediol-co-citrate) scaffold pore shape and permeability effects on sub-cutaneous in vivo chondrogenesis using primary chondrocytes. Acta Biomater 7:505-14
Mitsak, Anna G; Kemppainen, Jessica M; Harris, Matthew T et al. (2011) Effect of polycaprolactone scaffold permeability on bone regeneration in vivo. Tissue Eng Part A 17:1831-9
Jeong, Claire G; Hollister, Scott J (2010) Mechanical, permeability, and degradation properties of 3D designed poly(1,8 octanediol-co-citrate) scaffolds for soft tissue engineering. J Biomed Mater Res B Appl Biomater 93:141-9

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