AUTHOR=Yamaura Kohei , Sather Nicholas A. , Metlushko Anna , Nishimura Haruki , Pavlović Radoslav Z. , Hambright Sealy , Ravuri Sudheer K. , Philippon Marc J. , Stupp Samuel I. , Bahney Chelsea S. , Huard Johnny
TITLE=Sustained-release losartan from peptide nanofibers promotes chondrogenesis
JOURNAL=Frontiers in Bioengineering and Biotechnology
VOLUME=11
YEAR=2023
URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1122456
DOI=10.3389/fbioe.2023.1122456
ISSN=2296-4185
ABSTRACT=Introduction: The central pathologic feature of osteoarthritis (OA) is the progressive loss of articular cartilage, which has a limited regenerative capacity. The TGF-β1 inhibitor, losartan, can improve cartilage repair by promoting hyaline rather that fibrous cartilage tissue regeneration. However, there are concerns about side effects associated with oral administration and short retention within the joint following intra-articular injections. To facilitate local and sustained intra-articular losartan delivery we have designed an injectable peptide amphiphile (PA) nanofiber that binds losartan. The aims of this study are to characterize the release kinetics of losartan from two different PA nanofiber compositions followed by testing pro-regenerative bioactivity on chondrocytes.
Methods: We tested the impact of electrostatic interactions on nanostructure morphology and release kinetics of the negatively charged losartan molecule from either a positively or negatively charged PA nanofiber. Subsequently, cytotoxicity and bioactivity were evaluated in vitro in both normal and an IL-1β-induced OA chondrocyte model using ATDC5.
Results: Both nanofiber systems promoted cell proliferation but that the positively-charged nanofibers also significantly increased glycosaminoglycans production. Furthermore, gene expression analysis suggested that losartan-encapsulated nanofibers had significant anti-inflammatory, anti-degenerative, and cartilage regenerative effects by significantly blocking TGF-β1 in this in vitro system.
Discussion: The results of this study demonstrated that positively charged losartan sustained-release nanofibers may be a novel and useful treatment for cartilage regeneration and OA by blocking TGF-β1.