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 #
5R01AR062920-04
Application #
8900762
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Washabaugh, Charles H
Project Start
2012-08-01
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30318
Jang, Yeongseon; Choi, Won Tae; Johnson, Christopher T et al. (2018) Inhibition of Bacterial Adhesion on Nanotextured Stainless Steel 316L by Electrochemical Etching. ACS Biomater Sci Eng 4:90-97
Johnson, Christopher T; Wroe, James A; Agarwal, Rachit et al. (2018) Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing. Proc Natl Acad Sci U S A 115:E4960-E4969
Alas, Guillermo R; Agarwal, Rachit; Collard, David M et al. (2017) Peptide-functionalized poly[oligo(ethylene glycol) methacrylate] brushes on dopamine-coated stainless steel for controlled cell adhesion. Acta Biomater 59:108-116
Han, Woojin M; Jang, Young C; García, Andrés J (2017) Engineered matrices for skeletal muscle satellite cell engraftment and function. Matrix Biol 60-61:96-109
Moulisová, Vladimíra; Gonzalez-García, Cristina; Cantini, Marco et al. (2017) Engineered microenvironments for synergistic VEGF - Integrin signalling during vascularization. Biomaterials 126:61-74
Cruz-Acuña, Ricardo; García, Andrés J (2017) Synthetic hydrogels mimicking basement membrane matrices to promote cell-matrix interactions. Matrix Biol 57-58:324-333
Cruz-Acuña, Ricardo; Quirós, Miguel; Farkas, Attila E et al. (2017) Synthetic hydrogels for human intestinal organoid generation and colonic wound repair. Nat Cell Biol 19:1326-1335
Silva, Joana M; García, José R; Reis, Rui L et al. (2017) Tuning cell adhesive properties via layer-by-layer assembly of chitosan and alginate. Acta Biomater 51:279-293
Llopis-Hernández, Virginia; Cantini, Marco; González-García, Cristina et al. (2016) Material-driven fibronectin assembly for high-efficiency presentation of growth factors. Sci Adv 2:e1600188
García, José R; Clark, Amy Y; García, Andrés J (2016) Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects. J Biomed Mater Res A 104:889-900

Showing the most recent 10 out of 28 publications