Dual effect biodegradable ciprofloxacin loaded implantable matrices for osteomyelitis: controlled release and osteointegration

Abstract

Ciprofloxacin biodegradable implantable matrices (CPX-IMs) of tailored porous surfaces were fabricated by hot melt injection molding of poly-l-lactic acid (PLLA) followed by coating with PLLA/sodium chloride. CPX-IDs were designed to have a non-porous coat (NPC) or a porous coat of small pore size (SPC; 150-250 µm) or a large pore size (LPC; 250-350 µm). CPX-IMs surface pore size was confirmed by scanning electron microscope. The hardness of NPC, LPC, and SPC CPX-IMs were 58 ± 2.8, 53 ± 1.9, and 50 ± 2.1 N, respectively. The measured porosity values were 41.2 ± 1.53, 65.2 ± 1.1, and 60.7 ± 1.2%, respectively. Differential scanning calorimetry was employed to study the compatibility of ingredients, the effect of injection molding on polymer properties, and implants degradation. Coating of CPX-IMs prolonged drug release to reach a value of 90% release in 40 days. Antibacterial activity tests showed sufficiency of CPX to inhibit pathogens known to cause osteomyelitis. The in vivo study showed tissue compatibilities of the inserted matrices in tested rats with no sign of infection throughout the experiment period. SPC and LPC CPX-IMs demonstrated a better osteointegration, cell adhesion, and infiltration of different types of bone cells within implants structure compared to the non-porous matrix. Furthermore, LPC CPX-IMs showed a superior bone cell attachment and osteointegration relative to SPC CPX-IMs. Findings of this study confirmed the impact of porosity and pore sizes on cell proliferation and fracture healing concurrently with the sustained local antibiotic therapy for treatment or prevention of osteomyelitis.

In vitro and in vivo evaluation of a ciprofloxacin delivery system based on poly(DLLA-co-GA-co-CL) for treatment of chronic osteomyelitis

“…Finally, bone-cement monomers, such as PMMA, are moderately toxic. To circumvent these shortcomings, absorbable biomaterials [8][9][10][11][12][13][14] have been used to replace bone cement (e.g. PMMA) in the treatment of chronic osteomyelitis.…”

Biodegradable Bone Implants as a New Hope to Reduce Device-Associated Infections—A Systematic Review

“…Likewise, other antibiotics, such as imipenem/cilastatina (Tienam) [ 79 ] or a combination of gentamicin and clindamycin [ 81 ], were also used in scaffolds. Additional coatings were created by mixing levofloxacin with gold [ 90 ] and ciprofloxacin with PLLA and NaCl [ 91 ] ( Table 2 ).…”

“…Concerning the in vivo studies complemented by in vitro relevant data on microbiology analysis, only one study reported previously established infection in animals before implantation (10 days) [ 84 ]. Moreover, one article evaluated the presence of infection in vivo, even though no animals had been intentionally infected [ 91 ]. The remaining studies did not address infection in vivo [ 68 , 76 , 80 ].…”

Osteogenic Properties of Novel Methylsulfonylmethane-Coated Hydroxyapatite Scaffold

“…Dip-coating is the simplest technique that does not require substantial machinery and equipment [ 17 ]. In this method, the porous scaffold is dipped into the coating solution containing a specific drug-like chemical that would allow the ceramic scaffold to act as a carrier for the drug delivery system [ 18 , 19 , 20 ]. Many studies have demonstrated that scaffolds coated with the drug solution using the dip-coating technique are effective for bone tissue engineering [ 21 , 22 , 23 ].…”