Through modern surgical advancements, total hip replacements (THR) have become one of the most successful implant procedures to date. Even though long-term success rates are high, the staggering number of THR procedures per annum (~200,000 in the United States alone) results in thousands of failed implants each year. Most implants fail through aseptic loosening and implant instability. Earlier implant designs utilized synthetic bone cements that elicited a localized inflammatory response and stimulated bone resorption. In response, physicians shifted towards cementless implants-especially in active younger patients-and this implant design is now used in a majority of THR procedures. Unlike cemented implants, cementless implants achieve fixation by "press-fitting" porous titanium into bone. As such, adequate bone ingrowth is critical for patient recovery. Materials such as hydroxyapatite hasten bone ingrowth, but these coatings may promote osteolysis due to degradation. As an alternative, bone marrow- derived mesenchymal stem cells (BMSCs) may be used as a treatment to promote bone formation. Current methods utilize ex vivo BMSC culture that creates several practical and regulatory challenges. As an alternative, we have developed peptides that bind BMSCs with high specificity and affinity. Our goal is to coat these peptides onto hip implants in order to capture BMSCs from the implant's marrow-rich surroundings and capture them onto the implant surface. In preliminary studies, we have demonstrated that mineralization in stem cell cultures is dependent on cell concentration. Thus, we hypothesize that concentrating BMSCs on titanium implants will speed the patient recovery process and improve short-term clinical outcomes for cementless implants.

Public Health Relevance

Even though long-term success rates are high, the staggering number of THR procedures per annum (~200,000 in the United States alone) results in thousands of failed implants each year. Cementless implants now account for the majority of procedures, but adequate bone ingrowth is critical for patient recovery. We will develop coatings that promote bone formation by capturing stem cells from native host tissue.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AR066997-01
Application #
8780374
Study Section
Special Emphasis Panel (ZRG1-IMST-S (12))
Program Officer
Wang, Xibin
Project Start
2014-09-16
Project End
2015-08-31
Budget Start
2014-09-16
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$224,737
Indirect Cost
Name
Affinergy, LLC
Department
Type
DUNS #
078296854
City
Durham
State
NC
Country
United States
Zip Code
27713