Osteoarthritis (OA) is one of the most common forms of arthritis and characterized by progressive degradation of cartilage. There is no cure for OA and is a largely unmet medical need for disease-modifying and symptomatic treatment. Systemic delivery of morphogens and growth factors supporting cartilage matrix synthesis, such as insulin like growth factor-1 (IGF-1) and/or transforming growth factor- ? (TGF-?3), often results in poor improvement due to the lack of vascularity within intra-articular spaces. Therefore, localized intra-articular administration of growth factors targeting cartilage regeneration has emerged as a promising strategy for therapeutic intervention in OA. The objective of this R03 proposal is to develop nanosilicates for sustained delivery of OA-modifying therapeutics (IGF-1/ TGF-?3) to promote chondrocyte proliferation and maturation. Our central hypothesis is that sustain release of OA-modifying therapeutics will promote cartilaginous ECM production.
The specific aims of this work are: (1) Understand the biological response of nanosilicates with human cells, and (2) Investigate the efficacy of therapeutic loaded nanosilicates to induce chondrogenic differentiation and production of cartilaginous ECM. The proposed research has tremendous transformative potential in the areas of therapeutic delivery, cartilage regeneration, stem cell research and OA treatment. Specifically, this project will introduce nanosilicates as a ?plug-and-play? type of therapeutics delivery platform for various tissue-engineering applications. In addition, the project will also result in a fundamental shift in our understanding of mineral-induced cellular behavior, opening up an entirely new avenue in regenerative medicine. Upon completion, we believe that our results will have a significant, positive impact on regeneration of injured cartilage in patients suffering from osteoarthritis, for whom current treatment options remain limited. !

Public Health Relevance

We aim to develop a clinically relevant approach for osteoarthritis (OA) using mineral nanoparticles for controlled delivery of OA-modifying therapeutics. The sustain release of therapeutics will enhance cartilage regeneration by stimulating chondrocyte proliferation, maturation and cartilaginous ECM production. This platform will be a pivotal strategy for treating cartilage injuries at an early stage in an effort to ensure that they do not progress into arthritis, saving patients from a lifetime of pain, limited mobility, and long-term salvage procedures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Small Research Grants (R03)
Project #
1R03EB023454-01A1
Application #
9317847
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Hunziker, Rosemarie
Project Start
2017-04-01
Project End
2019-01-31
Budget Start
2017-04-01
Budget End
2018-01-31
Support Year
1
Fiscal Year
2017
Total Cost
$69,838
Indirect Cost
$19,838
Name
Texas Engineering Experiment Station
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
847205572
City
College Station
State
TX
Country
United States
Zip Code
77845
Gold, Karli; Gaharwar, Akhilesh K; Jain, Abhishek (2018) Emerging trends in multiscale modeling of vascular pathophysiology: Organ-on-a-chip and 3D printing. Biomaterials :
Clough, Bret H; Zeitouni, Suzanne; Krause, Ulf et al. (2018) Rapid Osteogenic Enhancement of Stem Cells in Human Bone Marrow Using a Glycogen-Synthease-Kinase-3-Beta Inhibitor Improves Osteogenic Efficacy In Vitro and In Vivo. Stem Cells Transl Med 7:342-353
Peak, Charles W; Stein, Jean; Gold, Karli A et al. (2018) Nanoengineered Colloidal Inks for 3D Bioprinting. Langmuir 34:917-925
Sheikhi, Amir; Afewerki, Samson; Oklu, Rahmi et al. (2018) Effect of ionic strength on shear-thinning nanoclay-polymer composite hydrogels. Biomater Sci 6:2073-2083
Carrow, James K; Cross, Lauren M; Reese, Robert W et al. (2018) Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates. Proc Natl Acad Sci U S A 115:E3905-E3913
Cross, Lauren M; Shah, Kunal; Palani, Sowmiya et al. (2018) Gradient nanocomposite hydrogels for interface tissue engineering. Nanomedicine 14:2465-2474
Jalili, Nima A; Jaiswal, Manish K; Peak, Charles W et al. (2017) Injectable nanoengineered stimuli-responsive hydrogels for on-demand and localized therapeutic delivery. Nanoscale 9:15379-15389
Meng, Zhaokai; Thakur, Teena; Chitrakar, Chandani et al. (2017) Assessment of Local Heterogeneity in Mechanical Properties of Nanostructured Hydrogel Networks. ACS Nano 11:7690-7696
Jalili, Nima A; Muscarello, Madyson; Gaharwar, Akhilesh K (2016) Nanoengineered thermoresponsive magnetic hydrogels for biomedical applications. Bioeng Transl Med 1:297-305
Cross, Lauren M; Thakur, Ashish; Jalili, Nima A et al. (2016) Nanoengineered biomaterials for repair and regeneration of orthopedic tissue interfaces. Acta Biomater 42:2-17