Porous titanium scaffolds modified with Zeolitic Imidazolate Framework (ZIF-8) with enhanced osteogenic activity for the prevention of implant-associated infections

Valentina Di Matteo; Maria Francesca Di Filippo; Barbara Ballarin; Francesca Bonvicini; Maria Rosa Iaquinta; Silvia Panzavolta; Elisa Mazzoni; Maria Cristina Cassani

doi:10.3389/fchem.2024.1452670

Porous titanium scaffolds modified with Zeolitic Imidazolate Framework (ZIF-8) with enhanced osteogenic activity for the prevention of implant-associated infections

Front Chem. 2024 Aug 29:12:1452670. doi: 10.3389/fchem.2024.1452670. eCollection 2024.

Authors

Valentina Di Matteo¹, Maria Francesca Di Filippo², Barbara Ballarin¹, Francesca Bonvicini³, Maria Rosa Iaquinta⁴, Silvia Panzavolta², Elisa Mazzoni^{5

6}, Maria Cristina Cassani¹

Affiliations

¹ Department of Industrial Chemistry "Toso Montanari", University of Bologna, Bologna, Italy.
² Department of Chemistry "G. Ciamician", University of Bologna, Bologna, Italy.
³ Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
⁴ Department of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara, Italy.
⁵ Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara, Italy.
⁶ Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.

Abstract

In this study, zeolitic imidazolate framework 8 (ZIF-8) was coated on porous Ti6Al4V scaffolds, either bare or previously modified using hydroxyapatite (HA) or HA and gelatin (HAgel), via a growing single-step method in aqueous media using two contact times at 6 h and 24 h. The coated scaffolds termed ZIF-8@Ti, ZIF-8@HA/Ti, and ZIF-8@HAgel/Ti were characterized via scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), and molecular plasma-atomic emission spectroscopy (MP-AES). In order to assess the cell proliferation rate, the cytocompatibility of the scaffolds was evaluated in primary osteoblasts (hOBs) using alamarBlue assay, while the osteoconductivity was analyzed in hOBs using a real-time approach, evaluating the expression of secreted phosphoprotein 1 (SPP1). Osteopontin, which is the protein encoded by this gene, represents the major non-collagenous bone protein that binds tightly to HA. The scaffolds were shown to be non-cytotoxic based on hOB proliferation at all time points of analysis (24 h and 72 h). In hOB cultures, the scaffolds induced the upregulation of SPP1 with different fold changes. Some selected scaffolds were assayed in vitro for their antibacterial potential against Staphylococcus epidermidis; the scaffolds coated with ZIF-8 crystals, regardless of the presence of HA and gelatin, strongly inhibited bacterial adhesion to the materials and reduced bacterial proliferation in the culture medium, demonstrating the suitable release of ZIF-8 in a bioactive form. These experiments suggest that the innovative scaffolds, tested herein, provide a good microenvironment for hOB adhesion, viability, and osteoconduction with effective prevention of S. epidermidis adhesion.

Keywords: anti-adhesion properties; bacterial infections; gelatin-A; hydroxyapatite; osteoblasts; titanium scaffolds; zeolitic imidazolate framework-8 (ZIF-8).

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. MC, SP, BB, and FB acknowledge financial support from the University of Bologna (RFO scheme); EM acknowledges a grant from Fondo di Ateneo per la Ricerca (FAR 2023).