Bone tissue deficiencies, including poor implant-bone integration, non-union fractures, and bone loss associated with diseases such as osteoporosis, trauma, joint replacements, and tumors, have tremendous socioeconomic impact in terms of disability and related health care costs. Biomaterial-based strategies to enhance implant osseointegration and bone formation will enable the development of biologically active and integrative orthopaedic and dental implant technologies to address these pressing clinical issues. The objective of this project is to engineer biomaterials presenting cell adhesive motifs that specifically bind to integrin receptors involved in bone formation in order to promote implant osseointegration and bone repair. Our central hypothesis is that precise presentation of pro-osteogenic, integrin-specific ligands will direct osteoblastic differentiation, implant osseointegration and bone repair. We have formulated this hypothesis based on our work with two engineered integrin-specific ligands that recapitulate the secondary structure of their native ligands (triple-helical GFOGER peptide from collagen-I for a2b1 integrin, recombinant FNIII7-10 from fibronectin for a5b1 integrin) and promote osteoblastic differentiation, implant osseointegration, and repair of bone defects.
Aim 1 : Engineer integrin-specific coatings that enhance screw-bone integration in healthy and ovariectomized rats.
Aim 2 : Engineer poly(ethylene glycol)-based hydrogels presenting integrin-specific ligands as grafting templates and BMP-2 delivery vehicles for the repair of non-healing bone defects. This research is innovative because it focuses on engineering novel biomaterial coatings and hydrogels with specificity for pro-osteogenic integrins to promote bone formation and repair. This work will establish the extent to which presentation of integrin-specific ligands enhances screw-bone integration in both healthy and osteoporotic bone. Also, we will engineer novel hydrogels as grafting materials and BMP-2 delivery vehicles for enhanced repair of non-healing bone defects. Collectively, these studies will establish novel bioactive materials that enhance bone formation and implant integration for improved bone repair in various clinical applications.

Public Health Relevance

Biomaterials play crucial roles in the treatment of bone deficiencies, but their performance is significantly limited by poor integration into bone and bone formation. We will engineer novel implant coatings and bone grafts that enhance implant-bone integration and bone repair. These materials will improve bone reconstruction procedures compared to present-day approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR062920-01
Application #
8304544
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$334,150
Indirect Cost
$109,150
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Johnson, Christopher T; García, Andrés J (2015) Scaffold-based anti-infection strategies in bone repair. Ann Biomed Eng 43:515-28
Lee, Ted T; García, José R; Paez, Julieta I et al. (2015) Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nat Mater 14:352-60
Garcia, Andres J (2014) PEG-maleimide hydrogels for protein and cell delivery in regenerative medicine. Ann Biomed Eng 42:312-22
Shekaran, Asha; Shoemaker, James T; Kavanaugh, Taylor E et al. (2014) The effect of conditional inactivation of beta 1 integrins using twist 2 Cre, Osterix Cre and osteocalcin Cre lines on skeletal phenotype. Bone 68:131-41
García, José R; García, Andrés J (2014) Cellular mechanotransduction: sensing rigidity. Nat Mater 13:539-40
Saxena, Shalini; Spears Jr, Mark W; Yoshida, Hiroaki et al. (2014) Microgel film dynamics modulate cell adhesion behavior. Soft Matter 10:1356-64
Shekaran, Asha; García, José R; Clark, Amy Y et al. (2014) Bone regeneration using an alpha 2 beta 1 integrin-specific hydrogel as a BMP-2 delivery vehicle. Biomaterials 35:5453-61
Frendl, Christopher M; Tucker, Scott M; Khan, Nadeem A et al. (2014) Endothelial retention and phenotype on carbonized cardiovascular implant surfaces. Biomaterials 35:7714-23
Cheng, Amy Y; Garcia, Andres J (2013) Engineering the matrix microenvironment for cell delivery and engraftment for tissue repair. Curr Opin Biotechnol 24:864-71