Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. Synthetic tissue engineering scaffolds provide a biomimetic construct, which employ natural biological cascades to promote healing, and native tissue integration and regeneration. As the role of cell signaling and subsequent functionality in tissue engineering becomes more clear, tissue engineers are developing multifunctional bioactive scaffolds designed to accelerate the natural healing process, which simultaneously prevent pathologies that may occur post-implantation. Ideal scaffolds are capable of presenting a physiochemical biomimetic environment while biodegrading as native tissue integrates and actively promotes or prevents desirable and undesirable physiological responses respectively. Thus, the hypotheses and specific aims of the proposed research program are:
Specific Aim 1 Develop processes for optimal fabrication of highly uniform micro/nano-hierarchal scaffolds of controllable geometry and bioactivity from PCL for orthopedic tissue engineering applications Specific Aim 2 Determine the effect of nanostructured surface morphology (size of nanowires) on the behavior of MSCs (adhesion, viability, morphology, differentiation, phenotype) both short term (days) and long term (several weeks) Specific Aim 3 Determine in vivo biocompatibility and oseointegration properties of micro/nano- hierarchal scaffolds Considering the limitations of the current gold-standard treatment for critical sized defects, biodegradable synthetic bone scaffolds hold a lot of promise for future treatment regimes. Therefore, synthetic bone tissue engineered scaffolds have been aggressively pursued in the last two decades, and now have emerged as a promising alternative to conventional therapies for repairing bone defects. The fundamental concept behind tissue engineering is to utilize the body's natural biological response to tissue damage in conjunction with engineering principles. Successful synthetic bone scaffolds promotes progenitor cell migration on to the scaffold (osteoconduction), support or induce osteogenic differentiation (osteoinduction), and finally integrate with host tissue (osseointegration). Additional critical aspects of successful bone scaffolds include biocompatibility, temporary mechanical stability, biodegradability, porosity, and controlled release of bioactive molecules to accelerate healing and/or prevent undesired pathologies. This proposed project outlines the motivation and reasoning behind the development of the PCL nanowire surfaces.

Public Health Relevance

Autogenous cancellous bone is currently the most widely used bone graft material. However, there are several problems associated with autogenous cancellous bone grafts such as additional scar tissue formation, donor site morbidity, pain, prolonged rehabilitation, increased risk of deep infection, inflammation and restricted availability. These problems have motivated the design of synthetic bone scaffolds as a replacement for autogenous cancellous bone grafts. This proposed project outlines the motivation and reasoning behind the development of the polymeric nanowire surfaces as a bone graft material.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AR057341-01A1
Application #
7990844
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2010-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$148,823
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Sorkin, Jonathan A; Hughes, Stephen; Soares, Paulo et al. (2015) Titania nanotube arrays as interfaces for neural prostheses. Mater Sci Eng C Mater Biol Appl 49:735-745
Leszczak, Victoria; Baskett, Dominique A; Popat, Ketul C (2015) Endothelial Cell Growth and Differentiation on Collagen-Immobilized Polycaprolactone Nanowire Surfaces. J Biomed Nanotechnol 11:1080-92
Leszczak, Victoria; Popat, Ketul C (2014) Improved in vitro blood compatibility of polycaprolactone nanowire surfaces. ACS Appl Mater Interfaces 6:15913-24
Damodaran, Vinod B; Leszczak, Victoria; Wold, Kathryn A et al. (2013) Anti-thrombogenic properties of a nitric oxide-releasing dextran derivative: evaluation of platelet activation and whole blood clotting kinetics. RSC Adv 3:
Bechara, Samuel; Popat, Ketul C (2013) Micro-patterned nanowire surfaces encourage directional neural progenitor cell adhesion and proliferation. J Biomed Nanotechnol 9:1698-706
Leszczak, Victoria; Smith, Barbara S; Popat, Ketul C (2013) Hemocompatibility of polymeric nanostructured surfaces. J Biomater Sci Polym Ed 24:1529-48
Bechara, Samuel; Wadman, Lucas; Popat, Ketul C (2011) Electroconductive polymeric nanowire templates facilitates in vitro C17.2 neural stem cell line adhesion, proliferation and differentiation. Acta Biomater 7:2892-901