Vasculo-osteogenic keratin-based nanofibers containing merwinite nanoparticles and sildenafil for bone tissue regeneration

Basma Talib Al-Sudani; Mastafa H Al-Musawi; Marwa M Kamil; Sumyah H Turki; Sepideh Nasiri-Harchegani; Aliakbar Najafinezhad; Parastoo Noory; Sina Talebi; Hamideh Valizadeh; Fariborz Sharifianjazi; Leila Bazli; Mohamadreza Tavakoli; Morteza Mehrjoo; Mahboubeh Firuzeh; Marjan Mirhaj

doi:10.1016/j.ijpharm.2024.124875

Vasculo-osteogenic keratin-based nanofibers containing merwinite nanoparticles and sildenafil for bone tissue regeneration

Int J Pharm. 2024 Oct 28;667(Pt A):124875. doi: 10.1016/j.ijpharm.2024.124875. Online ahead of print.

Authors

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.
² Department of Clinical Laboratory Sciences, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq. Electronic address: [email protected].
³ Department of Pharmaceutics, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq.
⁴ Department of Plant Biotechnology College of Biotechnology, Al-Nahrain University, Baghdad, Iraq.
⁵ Advanced Materials Research Center, Department of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran.
⁶ Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Department of Orthopaedics, Isfahan University of Medical Science, Isfahan, Iran.
⁸ Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
⁹ Department of Natural Sciences, School of Science and Technology, University of Georgia, Tbilisi 0171, Georgia.
¹⁰ School of Science and Technology, The University of Georgia, Tbilisi, Georgia.
¹¹ Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran.
¹² Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
¹³ Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran. Electronic address: [email protected].

PMID: 39471889
DOI: 10.1016/j.ijpharm.2024.124875

Abstract

Vascularization of bone tissue constructs plays a pivotal role in facilitating nutrient transport and metabolic waste removal during the processes of osteogenesis and bone regeneration in vivo. In this study, a sildenafil (Sil)-loaded nanofibrous scaffold of keratin/Soluplus/merwinite (KS.Me.Sil) was fabricated through electrospinning and the effectiveness of the scaffold was assessed for bone tissue engineering applications. The KS.Me.Sil nanofibrous scaffold exhibited notably enhanced ultimate tensile strength (3.38 vs 2.61 MPa) and elastic modulus (69.83 vs 46.27 MPa) compared to the KS scaffold. The in vitro release of Ca²⁺, Si⁴⁺ and Mg²⁺ ions and the release of Sil from the nanofibers as well as biodegradability and bioactivity were evaluated for 14 days. Protein adsorption capability and cytocompatibility of the scaffolds were tested. Alkaline phosphatase activity test, Alizarin red staining and qRT-PCR analysis demonstrated that the KS.Me.Sil nanofibers had the best osteogenic activity among other samples. Also, the results of the chorioallantoic membrane assay showed an almost threefold increase in blood vessel density in the group treated with the KS.Me.Sil nanofibers extract compared to the KS. In conclusion, our findings suggest that the electrospun KS.Me.Sil nanofibrous scaffold offers a robust structure with exceptional osteogenic and angiogenic characteristics, making it a promising candidate for bone tissue engineering applications.

Keywords: Electrospinning; In ovo vascularization; Keratin; Merwinite; Osteogenic differentiation; Sildenafil.