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Published on: April 15, 2017
Biomimetic Cardiac Fibrotic Model for Antifibrotic Drug Screening
Haiyan Li1, Yifan Zhu2, Zhe Chen1
1Department of Biomedical Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, P.R. China.
Abstract:
Cardiac fibrosis is characterized by pathological proliferation and activation of cardiac fibroblasts to myofibroblasts. Inhibition and reverse of transdifferentiation of cardiac fibroblasts to myofibroblasts is a potential strategy for cardiac fibrosis. Despite substantial progress, more effort is needed to discover effective drugs to improve and reverse cardiac fibrosis. The main reason for the slow development of antifibrotic drugs is that the traditional polystyrene culture platform does not recapitulate the microenvironment where cells reside in tissues. In this study, we propose an in vitro cardiac fibrotic model by seeding electrospun yarn scaffolds with cardiac fibroblasts. Our results show that yarn scaffolds allow three-dimensional growth of cardiac fibroblasts, promote extracellular matrix (ECM) deposition, and induce the transdifferentiation of cardiac fibroblasts to myofibroblasts. Exogenous transforming growth factor-β1 further promotes cardiac fibroblast activation and ECM deposition, which makes it a suitable fibrotic model to predict the antifibrotic potential of drugs. By using this platform, we demonstrate that both Honokiol (HKL) and Pirfenidone (PFD) show potential in antifibrosis to some extent. HKL is more efficient in antifibrosis than PFD as revealed by biochemical composition, gene, and molecular analyses as well as histological and biomechanical analysis. The electrospun yarn scaffold provides a novel platform for constructing in vitro fibrotic models to study cardiac fibrosis and to predict the antifibrotic efficacy of novel drugs.
Insights
A novel 3D cardiac fibrosis model using electrospun yarn scaffolds effectively mimics the in vivo environment. This platform demonstrates Honokiol is more potent than Pirfenidone in reversing cardiac fibrosis.
Area of Science:
- Biomaterials Science
- Cardiovascular Research
- Drug Discovery
Background:
- Cardiac fibrosis involves cardiac fibroblast activation and extracellular matrix (ECM) deposition.
- Current in vitro models fail to replicate the native tissue microenvironment, hindering antifibrotic drug development.
- Developing advanced models is crucial for effective cardiac fibrosis treatment strategies.
Purpose of the Study:
- To establish a novel in vitro cardiac fibrotic model using electrospun yarn scaffolds.
- To evaluate the antifibrotic potential of Honokiol (HKL) and Pirfenidone (PFD) using this new model.
- To compare the efficacy of HKL and PFD in reversing cardiac fibrosis.
Main Methods:
- Cardiac fibroblasts were seeded onto electrospun yarn scaffolds to create a 3D in vitro model.
- Transforming growth factor-β1 was used to induce fibrosis and promote ECM deposition.
- Biochemical, gene, molecular, histological, and biomechanical analyses were performed to assess fibrosis and drug efficacy.
Main Results:
- The electrospun yarn scaffold supported 3D fibroblast growth, ECM deposition, and myofibroblast differentiation.
- The model successfully recapitulated key features of cardiac fibrosis.
- Honokiol demonstrated superior antifibrotic effects compared to Pirfenidone.
Conclusions:
- Electrospun yarn scaffolds provide a robust platform for in vitro cardiac fibrosis modeling.
- This model can accurately predict the antifibrotic efficacy of potential drugs.
- Honokiol shows significant promise as an antifibrotic agent for cardiac fibrosis.
